Journal List > J Rheum Dis > v.30(3) > 1516083056

This article has been corrected. See "Corrigendum: Korean treatment recommendations for patients with axial spondyloarthritis" in Volume 31 on page 62.
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Seo, Yeo, Park, Lee, Lee, Kang, Ji, Kwon, Kim, Kim, Kim, Kim, Park, Shin, Lee, Lee, Cha, Shim, Yoon, Lee, Lim, Baek, and on behalf of the Korean Society of Spondyloarthritis Research: Korean treatment recommendations for patients with axial spondyloarthritis
Review Article

J Rheum Dis 2023;30(3):151-169.

Published online: 1 July 2023

DOI: https://doi.org/10.4078/jrd.2023.0025

Korean treatment recommendations for patients with axial spondyloarthritis

Mi Ryoung Seo, M.D.1, Jina Yeo, M.D.1, Jun Won Park, M.D.2, Yeon-Ah Lee, M.D., Ph.D.3, Ju Ho Lee, M.D.4, Eun Ha Kang, M.D., Ph.D.4, Seon Mi Ji, M.D., Ph.D.5, Seong-Ryul Kwon, M.D., Ph.D.6, Seong-Kyu Kim, M.D., Ph.D.7, Tae-Jong Kim, M.D., Ph.D.8, Tae-Hwan Kim, M.D., Ph.D.9, Hye Won Kim, M.D., Ph.D.10, Min-Chan Park, M.D., Ph.D.11, Kichul Shin, M.D., Ph.D.12, Sang-Hoon Lee, M.D., Ph.D.13, Eun Young Lee, M.D., Ph.D.2, Hoon Suk Cha, M.D., Ph.D.14, Seung Cheol Shim, M.D., Ph.D.15, Youngim Yoon, RN2, Seung Ho Lee, M.D., Ph.D.16, Jun Hong Lim, M.D., Ph.D.17, Han Joo Baek, M.D., Ph.D.1, ; on behalf of the Korean Society of Spondyloarthritis Research

1Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

2Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

3Division of Rheumatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea

4Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

5National Health Insurance Service, Wonju, Korea

6Division of Rheumatology, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea

7Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea

8Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea

9Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

10Division of General Internal Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

11Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

12Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea

13Department of Rheumatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea

14Division of Rheumatology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

15Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Korea

16Korea Ankylosing Spondylitis Society, Seoul, Korea

17Korea Ankylosing Spondylitis Corporation, Daejeon, Korea

Corresponding author: Han Joo Baek, https://orcid.org/0000-0001-7558-052X, Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea. E-mail: baekhj@gilhospital.com, This article is co-published by the Korean Journal of Internal Medicine and Journal of Rheumatic Diseases.

Received 3 May 2023       Revised 13 June 2023       Accepted 15 June 2023

Copyright © 2023 by The Korean College of Rheumatology. All rights reserved.

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Keywords: Axial spondyloarthritis, Ankylosing spondylitis, Treatment, Recommendations

INTRODUCTION

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease with axial, peripheral, and non-articular manifestations. It predominantly presents with axial manifestations, such as spondylitis and sacroiliitis; peripheral manifestations, including oligoarthritis, dactylitis, and enthesitis; and non-articular manifestations, including psoriasis, uveitis, and inflammatory bowel disease (IBD). AxSpA is classified as non-radiographic axSpA (nr-axSpA), an early stage of the disease, or ankylosing spondylitis (AS), diagnosed based on radiographic sacroiliitis that fulfills the modified New York criteria for AS [1]. Timely and appropriate treatment is necessary for axSpA, as it is a progressive disease that leads to irreversible structural damage, loss of spinal mobility, functional disability, and ultimately reduced quality of life (QoL).
Evidence-based treatment guidelines are essential for quality care and healthcare policymaking. Academic rheumatology societies, including the European Alliance of Association for Rheumatology (EULAR) and American College of Rheumatology (ACR), periodically publish and update official treatment recommendations and clinical practice guidelines [2-8]. There are variations in population characteristics, cultures, and medical systems across countries. Therefore, societal context is an important consideration when developing and adapting treatment recommendations.
Real-world practice is not consistent with evidence accumulated for the management of patients with axSpA. The use of biologics, such as tumor necrosis factor (TNF) inhibitors and interleukin (IL)-17 inhibitors, in pharmacological therapies has facilitated remarkable advances in axSpA treatment. Novel drugs such as Janus kinase (JAK) inhibitors have been introduced as therapeutic options against active axSpA. Non-Pharmacological management with exercise and surgery are also important in providing optimal care for patients with axSpA. Thus, comprehensive and evidence-based treatment recommendations covering both pharmacological and non-pharmacological therapies are essential to provide the best care for patients with axSpA.

RECOMMENDATION DEVELOPMENT

We referred to the standardized operating procedures of the EULAR and the National Evidence-based Healthcare Collaborating Agency to develop treatment recommendations for axSpA [9,10]. First, the convener organized the development committee (DC), which was responsible for developing the treatment recommendations, including the determination of key clinical questions (KCQs), selection of literature, review of evidence, and recommendation formulations. The DC comprised 18 rheumatologists from the Korean Society of Spondyloarthritis Research (KSSR) at the Korean College of Rheumatology (KCR), one methodologist, one nurse, and two patients from patient organizations. Seven rheumatologists and one methodologist comprised the core working group that coordinated and supported the development process, including systematic literature review and evidence synthesis. The DC established the operating terms and conditions, and conflict of interest management standards.
The DC made the following decisions: (1) the topic of recommendations was treatment for adult patients with axSpA, not including juvenile spondyloarthritis and psoriatic arthritis; (2) these recommendations cover overarching principles, treatment strategies, non-pharmacological and non-surgical treatments, pharmacological treatments, surgery, and monitoring; (3) target users of the recommendations are rheumatologists (primary) and physicians treating rheumatic and musculoskeletal disorders (secondary); and (4) healthcare settings covered by the recommendations ranged from primary clinics to tertiary hospitals.
After reviewing clinical questions regarding existing treatment guidelines for axSpA [2,5,7,8,11], the DC identified 88 KCQs after discussion and online surveys. The KCQs were described according to the population, intervention, comparator, and outcome (PICO) systems. Critical outcomes included musculoskeletal symptoms (pain, stiffness, and fatigue), QoL, mental health, disability, physical function, workability, safety, complications, comorbidities, and survival rate. Important outcomes included disease activity, treatment response, inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, structural damage on imaging, inflammation on magnetic resonance imaging (MRI), and spine mobility.
DC members identified Korean and English search terms for each KCQ. A literature search for Korean or English articles published between 1990 and 2021 was performed using the following databases: MEDLINE, Embase, Cochrane, KoreaMed, and KMbase (Korean Medical Database). Evidence from randomized controlled trials (RCTs) and/or high-quality comparative studies involving patients with axSpA aged 18 years or older was considered. Observational studies were included as evidence in the absence of RCTs or high-quality comparative studies. If required, manual searches were performed to obtain additional evidence. Finally, 160 reports were selected for supporting evidence. The risk of bias was assessed using the Cochrane risk of bias tool for randomized trials (RoB 2) [12]. The working group conducted systematic reviews and meta-analyses using RevMan software version 5.4 (Cochrane Collaboration, Oxford, UK). The grade of evidence (GoE) was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method (Table 1) [13].
The DC decided not to address 39 KCQs for which no quality evidence was found. Evidence for the remaining KCQs was summarized using the GRADE table and/or a summary of supporting studies [14]. Evidence and preliminary recommendations were presented to the DC members who discussed these at an off-line meeting and through online group chats. Some relevant items were combined into one recommendation. The strength of a recommendation (SoR) was described as “strong” or “weak” (Table 1) [15]. The verb “recommend” or “should” was used for strong recommendations; “suggest” or “can” was for weak recommendations. The formulated recommendations were prepared for voting on the consensus panel through further electronic surveys of the DC members.
The consensus-voting panel comprised the directors of the KCR, steering committee members of the KSSR, and members of the DC. The formulated recommendations, summaries of the evidence, and voting guidelines were presented to the panel. Voting was based on a level of agreement (LoA) scale from 1 to 5 (1, strongly disagree; 2, disagree; 3, neither agree nor disagree; 4, agree; and 5, strongly agree). Consensus was achieved if more than 80% of the panel voted 4 or 5 for a recommendation. Consensus was reached by the first vote on all recommendations, except for recommendation 12, for which it was reached by the second vote. Treatment recommendations for axSpA, comprising three overarching principles and twenty-one recommendations, were finalized (Table 2, Supplementary Table 1). A schematic of the final treatment recommendations was presented at the next DC meeting (Figure 1). The steering committee of the KSSR endorsed these recommendations on June 14, 2022.

RECOMMENDATIONS FOR THE TREATMENT OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Overarching principles

1) AxSpA is a potentially disabling inflammatory disease of the spine, often associated with articular, periarticular, or non-articular features (SoR, strong; LoA, 100%)

Overarching principle (OAP) 1 pertains to the definition of axSpA and reflects a comprehensive view of the disease. AxSpA is an inflammatory disease that can cause disability in patients’ daily lives. It involves not only the spine, but also peripheral joints and periarticular tissues. Many patients experience extra-musculoskeletal symptoms such as uveitis, IBD, and psoriasis [16-18].

2) The primary goal of management in axSpA is to maximize patients’ health-related QoL through control of symptoms and inflammation, prevention of structural damage, minimization of non-articular manifestations, and maintenance of function (SoR, strong; LoA, 100%)

The goal of caring for axSpA patients is to help them achieve the best health-related QoL (HrQoL). The main factors that determine the HrQoL in patients with axSpA include inflammatory activity, structural damage, and physical function [19,20]. As axSpA is fundamentally an inflammatory disease, controlling disease activity is important to relieve symptoms, prevent structural damage, and maintain and improve function and QoL [21-23]. Extra-musculoskeletal involvement is associated with decreased QoL and may be with increased cardiovascular risk and mortality [24-26]. Thus, controlling these symptoms in patients with axSpA is another concern. Similar to the treatment of other rheumatic and musculoskeletal disease, both pharmacological and non-pharmacological treatment such as education, physical therapy, and surgery should be used for optimal management of axSpA.

3) Treatment of axSpA should be based on shared decisions between the patient and physician, which usually requires multidisciplinary management coordinated by the rheumatologist (SoR, strong; LoA, 100%)

Quality care for individual patient is based on shared decision-making (SDM) between the patient and health professionals. In SDM, patient and caregivers work together to build a treatment plan that incorporates evidence-based information, clinical experts’ experiences, and patients’ preferences, values, and goals [27]. This includes determining the treatment objective, selecting the treatment method, and considering how to taper therapies if the treatment objective is achieved. SDM success requires provision of sufficient information to patients and appropriate trust and communication between patients and health professionals. Patient and physician commitment to SDM maximizes treatment concordance and success. SDM is strongly supported as a general principle and is foundational in treatment recommendations by international organizations such as the Assessment of SpondyloArthritis International Society (ASAS), EULAR, and ACR [28,29].
Care for patients with axSpA who show various clinical symptoms, including extra-musculoskeletal symptoms, and need both pharmacological and non-pharmacological treatment requires a multidisciplinary approach involving ophthalmologists, dermatologists, gastroenterologists, orthopedic surgeons, physiatrist, and other health professionals, along with rheumatologists. Multidisciplinary care is most effectively coordinated by rheumatologist who have a broad understanding of the spectrum of axSpA diagnoses, disease course, and treatments.

Recommendations

1) Treatment strategies

Recommendation 1. We recommend that the treatment of axSpA should be tailored for each patient using regular assessments of their clinical state and disease activity (GoE, very low; SoR, strong; LoA, 100%)

This recommendation was derived from the KCQs related to the treat-to-target (T2T) strategy and disease monitoring. There is considerable indirect evidence for effective disease monitoring in the management of axSpA [21,30-48]. Although treatment strategies for remission or low disease activity have attracted widespread attention to achieve the goal of care for patients with axSpA referred to in OAP2, the T2T strategy for ax SpA remains controversial. One RCT reported no significant difference between the T2T strategy and the traditional method in terms of the primary endpoint [49]. As it is difficult to judge the definite benefits of the T2T strategy, it was not directly included in this recommendation. However, the DC believes that individualized treatment adjustment using periodic evaluation of the patient’s clinical state centered on disease activity is essential; therefore, they strongly recommend it. Disease activity should be assessed using validated indicators such as the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [31-33].

Recommendation 2. We recommend collaboration with a relevant specialist for the diagnosis and treatment of extra-articular symptoms (GoE, very low; SoR, strong; LoA, 100%)

This recommendation is related with OAP3. Despite the limited direct evidence, recommendation 2 was strongly agreed upon by all the experts. IBD, uveitis, and psoriasis are common extra-musculoskeletal symptoms in patients with axSpA. The relevant specialists should participate in the diagnosis and management of these symptoms.

2) Non-pharmacological and non-surgical management

Recommendation 3. We recommend that education about axSpA should be provided to all patients (GoE, moderate; SoR, strong; LoA, 100%)

Education is crucial for patients with axSpA, who must cope with the disease and may not know it well. Most patients with axSpA wish to receive education on the disease, treatment, required exercises, and self-management. Patients who received education about axSpA showed better results of the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis QoL (ASQoL) compared to those who did not [50]. Patient education may also improve SDM and patient participation in treatment, as mentioned in OAP3.

Recommendation 4. We recommend smoking cessation and regular exercise (GoE, low; SoR, strong; LoA, 96.8%)

Smoking may be detrimental in terms of disease activity, bony progression, and QoL in patients with axSpA [37]. Considering this and the effects of smoking on general health, smoking cessation is strongly recommended. Exercise significantly improved fatigue and the BASFI and EuroQoL scores in patients with axSpA [50-54]. Supervised or institutional exercise better improved the BASDAI, BASFI and Bath Ankylosing Spondylitis Metrology Index (BASMI) scores, but did not differ from unsupervised or home-based exercise in terms of pain, chest expansion, and Bath AS patient global score [55-59]. Aquatic exercise was more beneficial for short-term pain and the modified Schober test results than was land-based exercise; however, the difference was modest [60]. Unfortunately, standardized axSpA-appropriate programs for supervised, institutional, or aquatic exercise are not easily accessible for patients. Passive physical therapy has been shown to have short-term effects; however, no studies have reported on its long-term effects [61,62]. Further, while manual therapy is popular, it remains unverified in terms of harmful effect in patients with axSpA [63]. Thus, we strongly recommend regular exercise without specifying the type and location of exercise, in consideration of accessibility and availability.

3) Pharmacological treatment in active disease

Recommendation 5. In patients with active axSpA, we recommend that treatment with a full-dose nonsteroidal anti-inflammatory drug (NSAID) should be initiated (GoE, high; SoR, strong; LoA, 96.8%)

Active axSpA refers to the presence of axial and/or peripheral symptoms attributed to inflammation, usually defined as a BASDAI score or ASDAS of >4.0 or ≥2.1, respectively [2,64]. NSAIDs have demonstrated significant beneficial effects on active axSpA in terms of outcome parameters such as pain and BASFI [65-67]. There are not certain NSAIDs being more advantageous in their efficacy than others [65-73]. However, a full dose of NSAIDs is more effective than a minimal dose in terms of the patient global assessment, ASAS20, and BASDAI scores [65,68-71]. Although worsening of occult bowel inflammation is a concern when using NSAIDs in patients with axSpA, there is no definite relationship between NSAID use and IBD exacerbation [74,75]. We strongly recommend a full-dose NSAID as the first-line therapy in patients with active axSpA. However, safety issues associated with long-term NSAID use remain a concern. In addition, NSAID use is restricted in patients with renal insufficiency, cardiovascular disease, peptic ulcer disease, aspirin-exacerbated respiratory disease, or advanced chronic liver disease. Therefore, as directed in Recommendation 1, in axSpA, NSAID use should be tailored for each patient according to the associated benefits and risks.

Recommendation 6. In patients with active axSpA resistant to NSAIDs therapy, we suggest that systemic glucocorticoids not be used, but local glucocorticoid injections be considered for active peripheral arthritis or isolated sacroiliitis (GoE, very low; SoR, weak; LoA, 90.3%)

Only one RCT reported that the short-term use of systemic glucocorticoid was effective in active axSpA refractory to NSAIDs therapy [76]. The efficacy of long-term systemic glucocorticoid treatment in patients with active axSpA has not been clarified, although it is associated with a high risk of adverse effects. Biological agents are good treatment options for patients with active axSpA despite NSAID use. Therefore, we suggest that systemic glucocorticoids not be used in these patients. Intraarticular glucocorticoid injections for peripheral arthritis are popular in rheumatology [77]. Although evidence of their efficacy in axSpA is scarce, experts have suggested that these injections might help control active peripheral arthritis in patients with axSpA. A small RCT reported that local glucocorticoid injections are effective in controlling isolated sacroiliitis in axSpA [78]. Appropriate evidence on the efficacy of local glucocorticoid injections for enthesitis in patients with axSpA, which could have a risk of causing tendon rupture, was unavailable. Therefore, we suggest consideration of local glucocorticoid injections only for active peripheral arthritis or isolated sacroiliitis resistant to NSAIDs in patients with axSpA.

Recommendation 7. In axSpA patients with active peripheral arthritis resistant to NSAIDs therapy, we suggest that an additional sulfasalazine (SSZ) be considered when biologic therapy is restricted by regulatory guidelines or not preferred by the patient (GoE, moderate; SoR, weak; LoA, 96.8%)

There is little evidence that conventional disease-modifying antirheumatic drugs such as methotrexate and leflunomide are effective in patients with axSpA who do not respond to initial NSAID therapy [79-81]. Although biologic therapy may be a more effective treatment option in these patients, SSZ demonstrated efficacy and is commonly used for peripheral arthritis in patients with axSpA [82-84]. A few studies that compared SSZ with biological agents showed that SSZ was effective in relieving peripheral symptoms in patients with active axSpA despite NSAID use [85,86]. Therefore, the DC conditionally recommends SSZ for active peripheral arthritis resistant to NSAID therapy, in cases where biologic therapy is not affordable or preferable, for patients with axSpA.

Recommendation 8. In patients with active axSpA resistant to NSAID therapy, we recommend treating with TNF inhibitors (GoE, high; SoR, strong; LoA, 100%)

In Korea, biological agents, including TNF inhibitors such as etarnercept, infliximab, adalimumab, and golimumab, and IL-17 inhibitors such as secukinumab and ixekizumab, have been approved and used to treat patients with axSpA. Compared with placebos, TNF inhibitors have pronounced effects on various parameters, including ASAS response criteria, disease activity, BASFI, BASMI, 36-item Short Form Survey (SF-36) scores, and peripheral symptoms, in patients with active axSpA despite NSAID treatment [87-105]. TNF inhibitors were more effective than SSZ for most parameters in these patients [85,87,89]. Therefore, we recommend the use of TNF inhibitor as initial biologic therapy for active axSpA despite NASID use. There is no evidence regarding certain TNF inhibitors being more effective than others [106].
Although IL-17 inhibitors are also recommended as initial biologic therapy in the recently published EULAR recommendations [107], we did not include IL-17 inhibitors as first-line biological therapy. While there is no evidence that TNF inhibitors are more effective than IL-17 inhibitors, TNF inhibitors are preferred as they have been studied more extensively and have been used in clinical practice for a longer time than have IL-17 inhibitors. Moreover, while switching to IL-17 inhibitors in case of insufficient response to TNF inhibitors has been reported, switching from IL-17 inhibitors to TNF inhibitors has not [108-110]. In other words, evidence regarding the pharmacological therapeutic pathway in cases of IL-17 inhibitor failure in patients with active axSpA is unavailable.
The DC did not address the criteria of initiation of biologic therapy in case of insufficient response to initial NSAID treatment. The reimbursement regulation of the Korean National Health Insurance regarding biological agents for AS patients defines that as BASDAI score of >4.0 despite of treatment with two or more NSAIDs for more than 3 months. This differs from the global standard, in which early initiation of biological agents is recommended, based on expert judgement, in patients with active axSpA (BASDAI >4.0 or ASDAS ≥2.1) despite the use of two or more NSAIDs consecutively for 1 month [2,3,5,8].
Safety in the use of biological agents has not been addressed in this recommendation and should be referred to in other recommendations [111].

Recommendation 9. In patients with active axSpA resistant to NSAID therapy who have uveitis or IBD, we suggest treatment with monoclonal TNF inhibitors as initial biological agents (GoE, low; SoR, weak; LoA 100%)

There are no direct RCTs related to the KCQs corresponding to this recommendation. Three observational studies and three meta-analyses showed that compared to fusion proteins (etanercept), monoclonal TNF inhibitors (infliximab and adalimumab) generally showed better outcomes in terms of the incidence or flare rates of uveitis or IBD [112-117]. Further, IL-17 inhibitors may exacerbate IBD in patients with axSpA [118].

Recommendation 10. In patients with active axSpA resistant to NSAID therapy who have significant psoriasis, we suggest consideration of IL-17 inhibitors as an alternative biologic therapy (GoE, high; SoR, weak; LoA, 96.8%)

IL-17 inhibitors were more effective than a placebo in patients who responded insufficiently to NSAID therapy [108,119-125]. In particular, IL-17 inhibitors were more effective than TNF inhibitors in treating psoriasis [126]. Therefore, IL-17 inhibitors can be considered the first-line biological agents for patients with axSpA with significant psoriasis, which corresponds to severe or extensive psoriasis and significantly affects QoL [127].

Recommendation 11. In patients with active axSpA resistant to a TNF inhibitor, we recommend switching to a different TNF inhibitor or to an IL-17 inhibitor (GoE, low; SoR, strong; LoA, 100%)

Switching to another TNF inhibitor is effective in a significant number of patients with axSpA, in cases of intolerance to or persistence of active disease with the first TNF inhibitor [128-133]. However, this appears less effective in patients with an initial lack of response than in those with relapse after first TNF inhibitor use [128]. IL-17 inhibitors have also demonstrated efficacy in patients with AS being refractory to or intolerant to the TNF inhibitors [108-110]. Therefore, in patients with axSpA with active disease resistant to a TNF inhibitor, we strongly recommend switching to a different TNF inhibitor or to an IL-17 inhibitor, irrespective of the presumed reason behind failure of the first TNF inhibitor.

Recommendation 12. In patients with active axSpA despite biologic therapy, JAK inhibitor use can be considered (GoE, very low; SoR, weak; LoA 80.6%)

Recently, JAK inhibitors, such as tofacitinib and upadacitinib, have shown significant effects on several outcomes, including the ASAS20, ASAS40, BASFI, BASMI, and ASDAS scores in patients with active axSpA with an insufficient response to NSAID therapy [134-136]. However, data regarding JAK inhibitor use in clinical practice remains scarce. Although there are no RCTs on the effectiveness of JAK inhibitors in patients with axSpA who have an insufficient response to biologic therapy, we conditionally suggest JAK inhibitor use in such patients.

4) Pharmacological treatment in stable disease

Recommendation 13. In patients with stable axSpA, we suggest treatment with on-demand NSAIDs rather than continuous NSAIDs (GoE, low; SoR, weak; LoA, 83.9%)

In axSpA, stable disease corresponds to an inactive disease state that persists for more than six months [2,3]. Long-term studies showed that continuous NSAID treatment was not better than on-demand NSAID treatment for inhibiting structural damage [137,138], and there was no statistical difference in the mean BASDAI and BASFI scores between patients with continuous and on-demand NSAID use over 24 months [138]. Long-term use of NSAIDs is associated with concerns regarding safety rather than their efficacy. Therefore, we suggest the use of on-demand NSAIDs over continuous NSAIDs for patients with stable axSpA.

Recommendation 14. In patients with stable axSpA, we suggest that biologic originators be replaced with biosimilars (GoE, moderate; SoR, weak; LoA, 83.9%)

A biosimilar is a biological agent with highly similar physicochemical characteristic and biological activities as the biological originator. Further preclinical and clinical studies are required to confirm their equivalent efficacy, safety, and immunogenicity [139-141]. Several biosimilars based on infliximab, etanercept, and adalimumab originators have been developed and approved for use in patients with axSpA. Biosimilars are intended to be used in the same manner as the originator biological agents, but physicians may prefer treating with originators because they usually have more experience with these. Although switching from an originators to a biosimilar can save costs, it may result in a nocebo response such as a subjective increase in disease activity or adverse events [141]. However, several studies have confirmed that there is no significant difference in the ASAS response criteria and adverse events between biosimilars and biological originators [142-144]. Biosimilars are used more and more in rheumatic diseases; this is true even among physicians and patients in Korea. The voting panel agreed that a biological originator can be replaced with a biosimilar in patients with stable axSpA.

Recommendation 15. In patients with axSpA in long-term remission, we suggest consideration of tapering of biologic therapy (GoE, moderate; SoR, weak; LoA, 96.8%)

The appropriateness of discontinuation or dose reduction for biological agents in well-controlled axSpA is a common and important question for both patients and physicians. Among patients with axSpA in long-term remission, discontinuation of biologic agents resulted in a higher flare rate, but biologic agent dose reduction by half or increasing dosing intervals resulted in well-maintained remission without flares when compared to that with continuation of biological agents [145-148]. Therefore, tapering of biologic therapy can be considered in these patients.
In axSpA, remission is a state in which both disease activity and progression are absent over a long period of time. However, there are currently no universally accepted criteria for remission in axSpA. Some authors have proposed the following remission criteria: ASDAS <1.3, absence of peripheral symptoms, absence of extra-articular symptoms, normal CRP levels, and absence of radiographic progression [149]. Herein, remission for over 6 (or 12) months could be considered long-term.

Recommendation 16. We suggest the addition of analgesics to control residual pain (GoE, low; SoR, weak; LoA, 87.1%)

Although the incidence of side effects increased slightly, the addition of analgesics, such as tramadol and acetaminophen, helped relieve pain in patients with axSpA [150]. Use of analgesics must not hinder or delay the appropriate anti-inflammatory therapies. When residual pain persists despite standard treatments, analgesics can be administered.

5) Complementary medicine

Recommendation 17. We suggest that spa and acupuncture not be provided to patients with axSpA as therapies (GoE, low; SoR, weak; LoA, 80.6%)

SpA and acupuncture are traditional complimentary remedies for controlling musculoskeletal pain that are familiar to Koreans. A few small studies showed that spas helped relieve symptoms and improve the QoL in patients with axSpA; however, these effects lasted for a short period [51,151,152]. Currently, there is no standardized spa therapy for patients with axSpA. Further, in a small RCT, acupuncture was not more effective than sham therapy [153]. Therefore, we suggest that spa and acupuncture not be used in patients with axSpA as therapies.

6) Surgical treatment

Recommendation 18. We recommend that total hip arthroplasty should be considered for patients with refractory pain or disability caused by radiographic hip destruction (GoE, very low; SoR, strong; LoA, 96.8%)

According to epidemiological data from Western countries, up to one-third of patients with AS have hip involvement [154]. Hip involvement is associated with significant functional decline in patients with axSpA, who may require hip arthroplasty. While hip involvement seems to be less frequent in Korean patients with AS, the rate of hip arthroplasty among patients with hip involvement is similar to that in foreign countries [155]. There are no RCTs on the effectiveness of total hip arthroplasty in patients with axSpA; however, many observational studies have suggested that total hip arthroplasty can reduce pain and improve joint range of motion and function [156-160]. This recommendation emphasizes that total hip arthroplasty is indicated in patients with axSpA who have severe pain or disability caused by hip destruction.

Recommendation 19. We suggest consideration of spinal surgery for acute spinal fracture in patients with axSpA (GoE, very low; SoR, weak; LoA, 83.9%)

Spinal fractures occurs more frequently and at younger ages in patients with axSpA than in controls [161-163]. In addition, axSpA is often accompanied by spinal cord injury, and the clinical outcome is worse in patients with axSpA than in those with general trauma [164-166]. Pain from spinal fractures may be overlooked due to axSpA disease activity, and patients’ abnormal vertebral structure makes radiographic evaluation difficult, often leading to a diagnostic delay [160,161]. Spinal fractures in patients with axSpA usually require surgery; however, conservative treatments are sometimes used when the surgical risk is extremely high. Observational studies have shown that surgery tends to further improve neurological outcomes and reduce complications when compared with conservative treatment [160]. In particular, patients with neurologic deficits or unstable fractures may require surgery, so immediate consultation with a surgeon is essential [167-169]. Therefore, we suggest acute spinal fractures as probable surgical indications in patients with axSpA.
Guidelines for vertebral osteotomy in patients with axSpA are conflicting. The EULAR/ASAS recommendations suggests that patients with severe kyphosis be considered for vertebral corrective osteotomy in a specialized center [107]; however, the ACR/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network guidelines conditionally recommend against elective spinal osteotomy, except in extreme cases, because of the postoperative mortality and neurological complications [3,11]. The DC has set aside recommendation on vertebral osteotomy for the future, considering the lack of specialized surgical institutions in Korea, the risk of surgery, and lower postoperative patient satisfaction. Arthroscopic synovectomy for active peripheral arthritis in patients with axSpA was excluded from the discussion because of a lack of evidence.

7) Monitoring of comorbidities and drug toxicities

Recommendation 20. We suggest monitoring and treating comorbidities such as cardiovascular disease and osteoporosis in patients with axSpA (GoE, very low; SoR, weak; LoA, 100%)

Comorbidities that can affect the patient mortality or QoL are important concerns for both patients and physicians during long-term care in chronic rheumatic diseases. Osteoporosis, posing a risk of spinal fractures, and cardiovascular diseases are frequently observed in patients with axSpA. In a large observational cohort, the incidence and prevalence of major adverse cardiovascular events in patients with axSpA were similar to those in patients with rheumatoid arthritis after adjusting for traditional cardiovascular risk factors, disease onset age, sex, and disease duration [170]. Patients with axSpA also have a higher prevalence of cardiovascular comorbidities, such as hypertension, dyslipidemia, and obesity, than dose the general population [171]. The bone mineral density of patients with AS is significantly lower than that of healthy controls [172,173]. Osteoporosis is found in approximately one quarter of patients with AS aged >50 years or with a disease duration of ≥10 years [174,175]. The voting panel agreed that monitoring and management of comorbidities in patients with axSpA, especially cardiovascular diseases and osteoporosis, is necessary.

Recommendation 21. We recommend that drug toxicities should be monitored in patients with axSpA on pharmacological therapy (GoE, very low; SoR, strong; LoA, 90.3%)

As there is a substantial possibility that all drugs cause toxicities, monitoring drug toxicity is essential for patient safety. Drug safety monitoring should be conducted for each drug taken by the patient [176]. This should be initiated by the physician with a clinical interview of the patient, considering their comorbidities and past medical history. Periodic blood tests, including complete blood count, liver function tests, and creatinine levels, are often required. Before using biological agents in patients with axSpA, surveillance of tuberculosis and hepatitis is required. Previously published consensus recommendations could be referred to on this [111].

CONCLUSION

Herein, recommendations, covering the comprehensive scope of management of adult patients with axSpA in a Korean context, were first developed based on clinical evidence. These consist of three overarching principles and 21 individual recommendation items, pertaining to treatment strategies, non-pharmacological and non-surgical management, pharmacological treatment in active and stable disease, complementary medicine, surgical treatment, and monitoring of comorbidities and drug toxicities.
However, these recommendations may be limited as some KCQs were not addressed owing to a lack of evidence. Additionally, we did not provide clear and specific consensus definitions of concepts essential for caring for patients, such as activity, remission, and treatment response. Further investigation and discussion are required to address these limitations. These recommendations will be updated when significant or substantial new evidence is identified by the KSSR at the KCR. We hope that these recommendations will guide best practice in the treatment of axSpA until then.

SUPPLEMENTARY DATA

Supplementary data can be found with this article online at https://doi.org/10.4078/jrd.2023.0025.
jrd-30-3-151-supple.pdf

ACKNOWLEDGMENTS

We thank Min Kyung Hyun, Dongguk University Graduate School of Korean Medicine; Yoon Jae Lee, Jaseng Medical Foundation for guidance on the methodology of the literature review and clinical guideline development; and all members of the voting panel: Hyun Sik Gong, Seoul National University Bundang Hospital; Jung Soo Song, Chung-Ang University School of Medicine; Wansik Uhm, Uhm’s Hanyang Rheumatism Clinic; Chong-Hyeon Yoon, Eunpyeong St. Mary’s Hospital, the Catholic University of Korea; Sangil Lee, Gyeongsang National University Hospital; Shin-Seok Lee, Chonnam National University Medical School and Hospital; Young Ho Lee, Korea university; Chang Keun Lee, Asan Medical Center, University of Ulsan college of medicine; Ji Hyeon Ju, The Catholic University of Korea; Seung-Jae Hong, Kyung Hee University Hospital.

Notes

FUNDING

This study was supported by the HANLIM Pharmaceutical and the KCR. The funders played no role in the study design, data collection, data analysis, data interpretation or manuscript writing.

CONFLICT OF INTEREST

M.R.S. received unrestricted grants from Hanlim Pharm, and speaker fees from Lilly. Y.A.L. received consulting and/or speaker fees from Astellas, Janssen, Lilly, AbbVie, and unrestricted grants from Celltrion. E.H.K. received unrestricted grants from Celltrion. S.R.K. received consulting and/or speaker fees from Janssen, Novartis, AbbVie, and unrestricted grants from Celltrion. S.K.K. has been an editorial board member since May 2018, but has no role in the decision to publish this article. T.J.K. received consulting and/or speaker fees from Janssen, AbbVie, Pfizer, and Novartis. T.H.K. received consulting and speaker fees from AbbVie, Novartis, Lilly, Janssen, and unrestricted grants from Yuhan Corporation. M.C.P. received consulting and/or speaker fees from Novartis, Lilly, AbbVie, Chong Kun Dang Pharm, JW Pharm, and research grants from Novartis, and has been an editorial board member since June 2014, but has no role in the decision to publish this article. S.H.L. received consulting and/or speaker fees from Novartis, Janssen, Lilly, AbbVie, Celltrion, and unrestricted grants from Celltrion. E.Y.L. received consulting or speaker fees from Lilly, JW Pharm, Novartis, Janssen, Samsung Bioepis and unrestricted grants from Yuhan Corporation. H.S.C. received consulting and/or speaker fees from LG Chem, Yuhan Corporation, AbbVie, Janssen, Novartis, and unrestricted grants from Celltrion. S.C.S. received consulting and/or speaker fees from AbbVie, Pfizer, Celltrion, Novartis, Astellas, JW Pharm, Chong Kun Dang Pharm, Amgen, and Otsuka Pharm. H.J.B. received consulting or speaker fees from Janssen, Astellas, Novartis, AbbVie, JW Pharm, Meranini, and unrestricted grants from Celltrion.

AUTHOR CONTRIBUTIONS

Conceptualization: S.M.J., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S, Y.Y., S.H.L., J.H.L., and H.J.B. Methodology: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.M.J., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S., and H.J.B. Resources: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S., and H.J.B. Investigation: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.M.J., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S, Y.Y., S.H.L., J.H.L., and H.J.B. Data curation: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S., and H.J.B. Formal analysis: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.M.J., and H.J.B. Validation: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.M.J., and H.J.B. Software: M.R.S., J.Y., J.W.P., Y.A.L., J.H.L., E.H.K., S.M.J., and H.J.B. Supervision: S.M.J., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S, Y.Y., S.H.L., J.H.L., and H.J.B. Project administration: H.J.B. Funding acquisition: H.J.B. Visualization: M.R.S., J.Y., and H.J.B. Writing-original draft: M.R.S., and H.J.B. Writing-review & editing: M.R.S., S.R.K., S.K.K., T.J.K., T.H.K., H.W.K., M.C.P., K.S., S.H.L., E.Y.L., H.S.C., S.C.S., Y.Y., S.H.L., J.H.L., and H.J.B.

REFERENCES

1. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Märker-Hermann E, Zeidler H, et al. 2009; The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 60:717–27. DOI: 10.1002/art.24483. PMID: 19248087.
crossref
2. van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, Sepriano A, et al. 2017; 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 76:978–91. DOI: 10.1136/annrheumdis-2016-210770. PMID: 28087505.
3. Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019; 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 71:1599–613. DOI: 10.1002/art.41042. PMID: 31436036. PMCID: PMC6764882.
crossref
4. Tam LS, Wei JC, Aggarwal A, Baek HJ, Cheung PP, Chiowchanwisawakit P, et al. 2019; 2018 APLAR axial spondyloarthritis treatment recommendations. Int J Rheum Dis. 22:340–56. DOI: 10.1111/1756-185X.13510. PMID: 30816645.
crossref
5. Rohekar S, Chan J, Tse SM, Haroon N, Chandran V, Bessette L, et al. 2015; 2014 Update of the Canadian Rheumatology Association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part I: principles of the management of spondyloarthritis in Canada. J Rheumatol. 42:654–64. DOI: 10.3899/jrheum.141000. PMID: 25684770.
crossref
6. Rohekar S, Chan J, Tse SM, Haroon N, Chandran V, Bessette L, et al. 2015; 2014 Update of the Canadian Rheumatology Association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part II: specific management recommendations. J Rheumatol. 42:665–81. DOI: 10.3899/jrheum.141001. PMID: 25684768.
crossref
7. Spanish Society of Rheumatology. ESPOGUIA Development Group. c2015. Clinical practice guideline for the treatment of patients with axial spondyloarthritis and psoriatic arthritis [Internet]. Spanish Society of Rheumatology;Madrid: https://www.ser.es/wp-content/uploads/2016/06/ENGLISH_updated_GPC_Treatment_SpondyloArthritis.pdf. cited 2023 Apr 17.
8. National Institute for Health and Care Excellence. c2017. Spondyloarthritis in over 16s: diagnosis and management [Internet]. National Institute for Health and Care Excellence;London: https://www.nice.org.uk/guidance/ng65. cited 2023 Apr 17.
9. van der Heijde D, Aletaha D, Carmona L, Edwards CJ, Kvien TK, Kouloumas M, et al. 2015; 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis. 74:8–13. DOI: 10.1136/annrheumdis-2014-206350. PMID: 25261577. PMCID: PMC4283681.
crossref
10. Kim SY, Choi M, Sheen SS, Ji SM, Park SH, You JH, et al. c2015. Handbook for clinical practice guideline devoloper [Internet]. National Evidence-based Healthcare Collaborating Agency;Seoul: https://www.neca.re.kr/SKIN_DIR/doc.html?fn=1611820150420175442.pdf&rs=/upload/synap/202304/. cited 2023 Apr 17.
11. Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. 2016; American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 68:282–98. DOI: 10.1002/art.39298. PMID: 26401991. PMCID: PMC5123840.
crossref
12. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. 2019; RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 366:l4898. DOI: 10.1136/bmj.l4898. PMID: 31462531.
crossref
13. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. 2011; GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 64:401–6. DOI: 10.1016/j.jclinepi.2010.07.015. PMID: 21208779.
crossref
14. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. 2011; GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 64:383–94. DOI: 10.1016/j.jclinepi.2010.04.026. PMID: 21195583.
crossref
15. Andrews J, Guyatt G, Oxman AD, Alderson P, Dahm P, Falck-Ytter Y, et al. 2013; GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol. 66:719–25. DOI: 10.1016/j.jclinepi.2012.03.013. PMID: 23312392.
crossref
16. Navarro-Compán V, Sepriano A, El-Zorkany B, van der Heijde D. 2021; Axial spondyloarthritis. Ann Rheum Dis. 80:1511–21. DOI: 10.1136/annrheumdis-2021-221035. PMID: 34615639.
crossref
17. Zink A, Braun J, Listing J, Wollenhaupt J. 2000; Disability and handicap in rheumatoid arthritis and ankylosing spondylitis--results from the German rheumatological database. German Collaborative Arthritis Centers. J Rheumatol. 27:613–22.
18. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. 2015; Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis. 74:65–73. DOI: 10.1136/annrheumdis-2013-203582. PMID: 23999006.
crossref
19. Machado P, Landewé R, Braun J, Hermann KG, Baraliakos X, Baker D, et al. 2011; A stratified model for health outcomes in ankylosing spondylitis. Ann Rheum Dis. 70:1758–64. DOI: 10.1136/ard.2011.150037. PMID: 21791453.
crossref
20. Hirano F, van der Heijde D, van Gaalen FA, Landewé RBM, Gaujoux-Viala C, Ramiro S. 2021; Determinants of the patient global assessment of well-being in early axial spondyloarthritis: 5-year longitudinal data from the DESIR cohort. Rheumatology (Oxford). 60:316–21. DOI: 10.1093/rheumatology/keaa353. PMID: 32766697. PMCID: PMC7785312.
crossref
21. Ramiro S, van der Heijde D, van Tubergen A, Stolwijk C, Dougados M, van den Bosch F, et al. 2014; Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Ann Rheum Dis. 73:1455–61. DOI: 10.1136/annrheumdis-2014-205178. PMID: 24812292.
crossref
22. Landewé R, Dougados M, Mielants H, van der Tempel H, van der Heijde D. 2009; Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis. 68:863–7. DOI: 10.1136/ard.2008.091793. PMID: 18628283.
crossref
23. van der Heijde D, Joshi A, Pangan AL, Chen N, Betts K, Mittal M, et al. 2016; ASAS40 and ASDAS clinical responses in the ABILITY-1 clinical trial translate to meaningful improvements in physical function, health-related quality of life and work productivity in patients with non-radiographic axial spondyloarthritis. Rheumatology (Oxford). 55:80–8. DOI: 10.1093/rheumatology/kev267. PMID: 26316575. PMCID: PMC4676905.
crossref
24. van der Meer R, Arends S, Kruidhof S, Bos R, Bootsma H, Wink F, et al. 2022; Extraskeletal manifestations in axial spondyloarthritis are associated with worse clinical outcomes despite the use of tumor necrosis factor inhibitor therapy. J Rheumatol. 49:157–64. DOI: 10.3899/jrheum.210308. PMID: 34393101.
crossref
25. Rueda-Gotor J, Ferraz-Amaro I, Genre F, González Mazón I, Corrales A, Portilla V, et al. 2022; Cardiovascular and disease-related features associated with extra-articular manifestations in axial spondyloarthritis. A multicenter study of 888 patients. Semin Arthritis Rheum. 57:152096. DOI: 10.1016/j.semarthrit.2022.152096. PMID: 36150319.
crossref
26. Kelty E, Ognjenovic M, Raymond WD, Inderjeeth CA, Keen HI, Preen DB, et al. 2022; Mortality rates in patients with ankylosing spondylitis with and without extraarticular manifestations and comorbidities: a retrospective cohort study. J Rheumatol. 49:688–93. DOI: 10.3899/jrheum.210909. PMID: 35428706.
crossref
27. Hargraves IG, Montori VM, Brito JP, Kunneman M, Shaw K, LaVecchia C, et al. 2019; Purposeful SDM: a problem-based approach to caring for patients with shared decision making. Patient Educ Couns. 102:1786–92. DOI: 10.1016/j.pec.2019.07.020. PMID: 31353170. PMCID: PMC6717012.
crossref
28. Nikiphorou E, Santos EJF, Marques A, Böhm P, Bijlsma JW, Daien CI, et al. 2021; 2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis. Ann Rheum Dis. 80:1278–85. DOI: 10.1136/annrheumdis-2021-220249. PMID: 33962964. PMCID: PMC8458093.
crossref
29. Morrison T, Foster E, Dougherty J, Barton J. 2022; Shared decision making in rheumatology: a scoping review. Semin Arthritis Rheum. 56:152041. DOI: 10.1016/j.semarthrit.2022.152041. PMID: 35738040.
crossref
30. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. 2004; Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis. 63:665–70. DOI: 10.1136/ard.2003.016386. PMID: 15037444. PMCID: PMC1755042.
31. Xu M, Lin Z, Deng X, Li L, Wei Y, Liao Z, et al. 2011; The Ankylosing Spondylitis Disease Activity Score is a highly discriminatory measure of disease activity and efficacy following tumour necrosis factor-α inhibitor therapies in ankylosing spondylitis and undifferentiated spondyloarthropathies in China. Rheumatology (Oxford). 50:1466–72. DOI: 10.1093/rheumatology/ker087. PMID: 21441550.
crossref
32. van der Heijde D, Lie E, Kvien TK, Sieper J, Van den Bosch F, Listing J, et al. 2009; ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 68:1811–8. DOI: 10.1136/ard.2008.100826. PMID: 19060001.
crossref
33. van der Heijde D, Braun J, Dougados M, Sieper J, Pedersen R, Szumski A, et al. 2012; Sensitivity and discriminatory ability of the Ankylosing Spondylitis Disease Activity Score in patients treated with etanercept or sulphasalazine in the ASCEND trial. Rheumatology (Oxford). 51:1894–905. DOI: 10.1093/rheumatology/kes142. PMID: 22772319.
crossref
34. Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A, Hsu B, et al. 2011; Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis. 70:973–81. Erratum. DOI: 10.1136/ard.2010.147744. PMID: 21402563. PMCID: PMC3086037.
crossref
35. Barlow JH, Wright CC, Williams B, Keat A. 2001; Work disability among people with ankylosing spondylitis. Arthritis Rheum. 45:424–9. DOI: 10.1002/1529-0131(200110)45:5<424::AID-ART361>3.0.CO;2-7. PMID: 11642641.
crossref
36. Machado P, Landewé R, Braun J, Hermann KG, Baker D, van der Heijde D. 2010; Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis. Ann Rheum Dis. 69:1465–70. DOI: 10.1136/ard.2009.124206. PMID: 20498215.
crossref
37. Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al. 2012; Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 64:1388–98. DOI: 10.1002/art.33465. PMID: 22127957.
crossref
38. Braun J, Deodhar A, Landewé R, Baraliakos X, Miceli-Richard C, Sieper J, et al. 2018; Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies. RMD Open. 4:e000749. DOI: 10.1136/rmdopen-2018-000749. PMID: 30564451. PMCID: PMC6269637.
crossref
39. Braun J, Baraliakos X, Hermann KG, Xu S, Hsu B. 2016; Serum C-reactive protein levels demonstrate predictive value for radiographic and magnetic resonance imaging outcomes in patients with active ankylosing spondylitis treated with golimumab. J Rheumatol. 43:1704–12. DOI: 10.3899/jrheum.160003. PMID: 27422890.
crossref
40. Benhamou M, Gossec L, Dougados M. 2010; Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/coxibs' treatment effect on C-reactive protein. Rheumatology (Oxford). 49:536–41. DOI: 10.1093/rheumatology/kep393. PMID: 20028728.
crossref
41. Baraliakos X, Szumski A, Koenig AS, Jones H. 2019; The role of C-reactive protein as a predictor of treatment response in patients with ankylosing spondylitis. Semin Arthritis Rheum. 48:997–1004. DOI: 10.1016/j.semarthrit.2018.10.019. PMID: 30473179.
crossref
42. Song IH, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, et al. 2016; Inflammatory and fatty lesions in the spine and sacroiliac joints on whole-body MRI in early axial spondyloarthritis--3-year data of the ESTHER trial. Semin Arthritis Rheum. 45:404–10. DOI: 10.1016/j.semarthrit.2015.08.005. PMID: 26519007.
crossref
43. Baraliakos X, Davis J, Tsuji W, Braun J. 2005; Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept. Arthritis Rheum. 52:1216–23. DOI: 10.1002/art.20977. PMID: 15818694.
crossref
44. Chiowchanwisawakit P, Lambert RG, Conner-Spady B, Maksymowych WP. 2011; Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis. Arthritis Rheum. 63:2215–25. DOI: 10.1002/art.30393. PMID: 21484769.
crossref
45. Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Østergaard M, Lambert RG. 2009; Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthritis Rheum. 60:93–102. DOI: 10.1002/art.24132. PMID: 19116919.
crossref
46. Rudwaleit M, Schwarzlose S, Hilgert ES, Listing J, Braun J, Sieper J. 2008; MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Ann Rheum Dis. 67:1276–81. DOI: 10.1136/ard.2007.073098. PMID: 18006539.
crossref
47. Machado P, Landewé RB, Braun J, Baraliakos X, Hermann KG, Hsu B, et al. 2012; MRI inflammation and its relation with measures of clinical disease activity and different treatment responses in patients with ankylosing spondylitis treated with a tumour necrosis factor inhibitor. Ann Rheum Dis. 71:2002–5. DOI: 10.1136/annrheumdis-2012-201999. PMID: 22915615.
crossref
48. Machado PM, Baraliakos X, van der Heijde D, Braun J, Landewé R. 2016; MRI vertebral corner inflammation followed by fat deposition is the strongest contributor to the development of new bone at the same vertebral corner: a multilevel longitudinal analysis in patients with ankylosing spondylitis. Ann Rheum Dis. 75:1486–93. DOI: 10.1136/annrheumdis-2015-208011. PMID: 26462728.
crossref
49. Molto A, López-Medina C, Van den Bosch FE, Boonen A, Webers C, Dernis E, et al. 2021; Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial. Ann Rheum Dis. 80:1436–44. DOI: 10.1136/annrheumdis-2020-219585. PMID: 33958325. PMCID: PMC8522451.
crossref
50. Rodríguez-Lozano C, Juanola X, Cruz-Martínez J, Peña-Arrébola A, Mulero J, Gratacós J, et al. 2013; Outcome of an education and home-based exercise programme for patients with ankylosing spondylitis: a nationwide randomized study. Clin Exp Rheumatol. 31:739–48.
51. Ciprian L, Lo Nigro A, Rizzo M, Gava A, Ramonda R, Punzi L, et al. 2013; The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors. Rheumatol Int. 33:241–5. DOI: 10.1007/s00296-011-2147-9. PMID: 21947374.
crossref
52. Altan L, Korkmaz N, Dizdar M, Yurtkuran M. 2012; Effect of Pilates training on people with ankylosing spondylitis. Rheumatol Int. 32:2093–9. DOI: 10.1007/s00296-011-1932-9. PMID: 21499876.
crossref
53. Sveaas SH, Dagfinrud H, Berg IJ, Provan SA, Johansen MW, Pedersen E, et al. 2020; High-intensity exercise improves fatigue, sleep, and mood in patients with axial spondyloarthritis: secondary analysis of a randomized controlled trial. Phys Ther. 100:1323–32. DOI: 10.1093/ptj/pzaa086. PMID: 32367124. PMCID: PMC7439225.
crossref
54. Sweeney S, Taylor G, Calin A. 2002; The effect of a home based exercise intervention package on outcome in ankylosing spondylitis: a randomized controlled trial. J Rheumatol. 29:763–6.
55. Kjeken I, Bø I, Rønningen A, Spada C, Mowinckel P, Hagen KB, et al. 2013; A three-week multidisciplinary in-patient rehabilitation programme had positive long-term effects in patients with ankylosing spondylitis: randomized controlled trial. J Rehabil Med. 45:260–7. DOI: 10.2340/16501977-1078. PMID: 23138412.
crossref
56. Aydın T, Taşpınar Ö, Sarıyıldız MA, Güneşer M, Keskin Y, Canbaz N, et al. 2016; Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with ankylosing spondylitis. J Back Musculoskelet Rehabil. 29:723–30. DOI: 10.3233/BMR-160677. PMID: 26966823.
crossref
57. Viitanen JV, Heikkilä S. 2001; Functional changes in patients with spondylarthropathy. A controlled trial of the effects of short-term rehabilitation and 3-year follow-up. Rheumatol Int. 20:211–4. DOI: 10.1007/s002960100101. PMID: 11518042.
crossref
58. Widberg K, Karimi H, Hafström I. 2009; Self- and manual mobilization improves spine mobility in men with ankylosing spondylitis--a randomized study. Clin Rehabil. 23:599–608. DOI: 10.1177/0269215508101748. PMID: 19403551.
crossref
59. Analay Y, Ozcan E, Karan A, Diracoglu D, Aydin R. 2003; The effectiveness of intensive group exercise on patients with ankylosing spondylitis. Clin Rehabil. 17:631–6. DOI: 10.1191/0269215503cr658oa. PMID: 12971708.
crossref
60. Dundar U, Solak O, Toktas H, Demirdal US, Subasi V, Kavuncu V, et al. 2014; Effect of aquatic exercise on ankylosing spondylitis: a randomized controlled trial. Rheumatol Int. 34:1505–11. DOI: 10.1007/s00296-014-2980-8. PMID: 24626605.
crossref
61. Stasinopoulos D, Papadopoulos K, Lamnisos D, Stergioulas A. 2016; LLLT for the management of patients with ankylosing spondylitis. Lasers Med Sci. 31:459–69. DOI: 10.1007/s10103-016-1874-2. PMID: 26796709.
crossref
62. Stanek A, Cholewka A, Wielkoszyński T, Romuk E, Sieroń A. 2018; Whole-body cryotherapy decreases the levels of inflammatory, oxidative stress, and atherosclerosis plaque markers in male patients with active-phase ankylosing spondylitis in the absence of classical cardiovascular risk factors. Mediators Inflamm. 2018:8592532. DOI: 10.1155/2018/8592532. PMID: 29483842. PMCID: PMC5816841.
crossref
63. Liao CC, Chen LR. 2007; Anterior and posterior fixation of a cervical fracture induced by chiropractic spinal manipulation in ankylosing spondylitis: a case report. J Trauma. 63:E90–4. DOI: 10.1097/01.ta.0000246957.22573.63. PMID: 18089996.
crossref
64. Machado P, Landewé R, Lie E, Kvien TK, Braun J, Baker D, et al. 2011; Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 70:47–53. DOI: 10.1136/ard.2010.138594. PMID: 21068095.
crossref
65. Barkhuizen A, Steinfeld S, Robbins J, West C, Coombs J, Zwillich S. 2006; Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis. J Rheumatol. 33:1805–12.
66. Dougados M, Béhier JM, Jolchine I, Calin A, van der Heijde D, Olivieri I, et al. 2001; Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Arthritis Rheum. 44:180–5. DOI: 10.1002/1529-0131(200101)44:1<180::AID-ANR24>3.0.CO;2-K. PMID: 11212158.
crossref
67. van der Heijde D, Baraf HS, Ramos-Remus C, Calin A, Weaver AL, Schiff M, et al. 2005; Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 52:1205–15. DOI: 10.1002/art.20985. PMID: 15818702.
crossref
68. Gao GM, Li YM, Zheng XL, Jiang DB, Zhang LL, Xu PH, et al. 2017; A randomized comparison study of therapy effects of two doses of imrecoxib with celecoxib on axial spondyloarthritis. Lat Am J Pharm. 36:308–13.
69. Balazcs E, Sieper J, Bickham K, Mehta A, Frontera N, Stryszak P, et al. 2016; A randomized, clinical trial to assess the relative efficacy and tolerability of two doses of etoricoxib versus naproxen in patients with ankylosing spondylitis. BMC Musculoskelet Disord. 17:426. DOI: 10.1186/s12891-016-1275-5. PMID: 27737664. PMCID: PMC5062857.
crossref
70. Walker C, Essex MN, Li C, Park PW. 2016; Celecoxib versus diclofenac for the treatment of ankylosing spondylitis: 12-week randomized study in Norwegian patients. J Int Med Res. 44:483–95. DOI: 10.1177/0300060516628704. PMID: 26980340. PMCID: PMC5536700.
crossref
71. Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al. 2008; Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. 67:323–9. DOI: 10.1136/ard.2007.075309. PMID: 17616556.
crossref
72. Huang F, Gu J, Liu Y, Zhu P, Zheng Y, Fu J, et al. 2014; Efficacy and safety of celecoxib in Chinese patients with ankylosing spondylitis: a 6-week randomized, double-blinded study with 6-week open-label extension treatment. Curr Ther Res Clin Exp. 76:126–33. DOI: 10.1016/j.curtheres.2014.08.002. PMID: 25516774. PMCID: PMC4266770.
crossref
73. Batlle-Gualda E, Figueroa M, Ivorra J, Raber A. 1996; The efficacy and tolerability of aceclofenac in the treatment of patients with ankylosing spondylitis: a multicenter controlled clinical trial. Aceclofenac indomethacin study group. J Rheumatol. 23:1200–6.
74. Miao XP, Li JS, Ouyang Q, Hu RW, Zhang Y, Li HY. Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease. Cochrane Database Syst Rev 2014;(10):CD007744. DOI: 10.1002/14651858.CD007744.pub2. PMID: 25340915.
crossref
75. Moninuola OO, Milligan W, Lochhead P, Khalili H. 2018; Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation. Aliment Pharmacol Ther. 47:1428–39. DOI: 10.1111/apt.14606. PMID: 29620794. PMCID: PMC5992031.
crossref
76. Haibel H, Fendler C, Listing J, Callhoff J, Braun J, Sieper J. 2014; Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial. Ann Rheum Dis. 73:243–6. DOI: 10.1136/annrheumdis-2012-203055. PMID: 23625982.
crossref
77. Rodriguez-García SC, Castellanos-Moreira R, Uson J, Naredo E, O'Neill TW, Doherty M, et al. 2021; Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews. RMD Open. 7:e001658. DOI: 10.1136/rmdopen-2021-001658. PMID: 34103406. PMCID: PMC8186751.
crossref
78. Maugars Y, Mathis C, Berthelot JM, Charlier C, Prost A. 1996; Assessment of the efficacy of sacroiliac corticosteroid injections in spondylarthropathies: a double-blind study. Br J Rheumatol. 35:767–70. DOI: 10.1093/rheumatology/35.8.767. PMID: 8761190.
79. Altan L, Bingöl U, Karakoç Y, Aydiner S, Yurtkuran M, Yurtkuran M. 2001; Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol. 30:255–9. DOI: 10.1080/03009740410005089.
crossref
80. van Denderen JC, van der Paardt M, Nurmohamed MT, de Ryck YM, Dijkmans BA, van der Horst-Bruinsma IE. 2005; Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis. 64:1761–4. DOI: 10.1136/ard.2005.036491. PMID: 15901634. PMCID: PMC1755327.
crossref
81. Gonzalez-Lopez L, Garcia-Gonzalez A, Vazquez-Del-Mercado M, Muñoz-Valle JF, Gamez-Nava JI. 2004; Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. J Rheumatol. 31:1568–74.
82. Clegg DO, Reda DJ, Weisman MH, Blackburn WD, Cush JJ, Cannon GW, et al. 1996; Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A department of veterans affairs cooperative study. Arthritis Rheum. 39:2004–12. DOI: 10.1002/art.1780391209. PMID: 8961905.
crossref
83. Khanna Sharma S, Kadiyala V, Naidu G, Dhir V. 2018; A randomized controlled trial to study the efficacy of sulfasalazine for axial disease in ankylosing spondylitis. Int J Rheum Dis. 21:308–14. DOI: 10.1111/1756-185X.13124. PMID: 28737251.
crossref
84. Braun J, Zochling J, Baraliakos X, Alten R, Burmester G, Grasedyck K, et al. 2006; Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis. 65:1147–53. DOI: 10.1136/ard.2006.052878. PMID: 16606646. PMCID: PMC1798286.
crossref
85. Braun J, Pavelka K, Ramos-Remus C, Dimic A, Vlahos B, Freundlich B, et al. 2012; Clinical efficacy of etanercept versus sulfasalazine in ankylosing spondylitis subjects with peripheral joint involvement. J Rheumatol. 39:836–40. DOI: 10.3899/jrheum.110885. PMID: 22337244.
crossref
86. Song IH, Hermann K, Haibel H, Althoff CE, Listing J, Burmester G, et al. 2011; Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial. Ann Rheum Dis. 70:590–6. Erratum. DOI: 10.1136/ard.2010.139667. PMID: 21372193. PMCID: PMC3211465.
crossref
87. Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, et al. 2011; Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum. 63:1543–51. DOI: 10.1002/art.30223.
crossref
88. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. 2006; Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54:2136–46. DOI: 10.1002/art.21913. PMID: 16802350.
crossref
89. Damjanov N, Shehhi WA, Huang F, Kotak S, Burgos-Vargas R, Shirazy K, et al. 2016; Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia. Rheumatol Int. 36:643–51. DOI: 10.1007/s00296-016-3452-0. PMID: 26968844.
crossref
90. Inman RD, Maksymowych WP. 2010; A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol. 37:1203–10. DOI: 10.3899/jrheum.091042. PMID: 20231198.
crossref
91. Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. 2015; A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 67:2702–12. DOI: 10.1002/art.39257. PMID: 26139307. PMCID: PMC4755041.
crossref
92. Hu Z, Xu M, Li Q, Lin Z, Liao Z, Cao S, et al. 2012; Adalimumab significantly reduces inflammation and serum DKK-1 level but increases fatty deposition in lumbar spine in active ankylosing spondylitis. Int J Rheum Dis. 15:358–65. DOI: 10.1111/j.1756-185X.2012.01734.x. PMID: 22898215.
crossref
93. Huang F, Gu J, Zhu P, Bao C, Xu J, Xu H, et al. 2014; Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial. Ann Rheum Dis. 73:587–94. DOI: 10.1136/annrheumdis-2012-202533. PMID: 23475983.
crossref
94. Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. 2013; Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 72:815–22. DOI: 10.1136/annrheumdis-2012-201766. PMID: 22772328. PMCID: PMC3664374.
crossref
95. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. 2008; Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 58:3402–12. DOI: 10.1002/art.23969. PMID: 18975305.
crossref
96. van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, et al. 2005; Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 52:582–91. DOI: 10.1002/art.20852. PMID: 15692973.
crossref
97. Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, et al. 2008; Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 58:1981–91. DOI: 10.1002/art.23606. PMID: 18576337.
crossref
98. Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P, et al. 2011; Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis. 70:799–804. Erratum. DOI: 10.1136/ard.2010.139261. PMID: 21317434. PMCID: PMC3070274.
crossref
99. Dougados M, Tsai WC, Saaibi DL, Bonin R, Bukowski J, Pedersen R, et al. 2015; Evaluation of health outcomes with etanercept treatment in patients with early nonradiographic axial spondyloarthritis. J Rheumatol. 42:1835–41. DOI: 10.3899/jrheum.141313. PMID: 26276968.
crossref
100. Davis JC Jr, Revicki D, van der Heijde DM, Rentz AM, Wong RL, Kupper H, et al. 2007; Health-related quality of life outcomes in patients with active ankylosing spondylitis treated with adalimumab: results from a randomized controlled study. Arthritis Rheum. 57:1050–7. DOI: 10.1002/art.22887. PMID: 17665483.
crossref
101. Deodhar A, Reveille JD, Harrison DD, Kim L, Lo KH, Leu JH, et al. 2018; Safety and efficacy of golimumab administered intravenously in adults with ankylosing spondylitis: results through week 28 of the GO-ALIVE study. J Rheumatol. 45:341–8. Erratum. DOI: 10.3899/jrheum.170487. PMID: 29247154.
crossref
102. Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. 2014; Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 66:2091–102. DOI: 10.1002/art.38721. PMID: 24891317.
crossref
103. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, et al. 2002; Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 359:1187–93. DOI: 10.1016/S0140-6736(02)08215-6. PMID: 11955536.
crossref
104. Dougados M, Combe B, Braun J, Landewé R, Sibilia J, Cantagrel A, et al. 2010; A randomised, multicentre, double-blind, placebo-controlled trial of etanercept in adults with refractory heel enthesitis in spondyloarthritis: the HEEL trial. Ann Rheum Dis. 69:1430–5. DOI: 10.1136/ard.2009.121533. PMID: 20511606.
crossref
105. van der Heijde D, Braun J, Deodhar A, Inman RD, Xu S, Mack ME, et al. 2013; Comparison of three enthesitis indices in a multicentre, randomized, placebo-controlled trial of golimumab in ankylosing spondylitis (GO-RAISE). Rheumatology (Oxford). 52:321–5. DOI: 10.1093/rheumatology/kes251. PMID: 23024015.
crossref
106. Giardina AR, Ferrante A, Ciccia F, Impastato R, Miceli MC, Principato A, et al. 2010; A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis. Rheumatol Int. 30:1437–40. DOI: 10.1007/s00296-009-1157-3. PMID: 19851772.
crossref
107. Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, et al. 2023; ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 82:19–34. DOI: 10.1136/ard-2022-223296. PMID: 36270658.
108. Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H, et al. 2017; Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther. 19:285. DOI: 10.1186/s13075-017-1490-y. PMID: 29273067. PMCID: PMC5741872.
crossref
109. Sieper J, Deodhar A, Marzo-Ortega H, Aelion JA, Blanco R, Jui-Cheng T, et al. 2017; Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis. 76:571–92. DOI: 10.1136/annrheumdis-2016-210023. PMID: 27582421.
crossref
110. Deodhar A, Poddubnyy D, Pacheco-Tena C, Salvarani C, Lespessailles E, Rahman P, et al. 2019; Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 71:599–611. DOI: 10.1002/art.40753. PMID: 30343531. PMCID: PMC6593790.
crossref
111. Park EJ, Kim H, Jung SM, Sung YK, Baek HJ, Lee J. 2020; The use of biological disease-modifying antirheumatic drugs for inflammatory arthritis in Korea: results of a Korean Expert Consensus. Korean J Intern Med. 35:41–59. DOI: 10.3904/kjim.2019.411. PMID: 31935319. PMCID: PMC6960050.
crossref
112. Kim M, Won JY, Choi SY, Ju JH, Park YH. 2016; Anti-TNFα treatment for HLA-B27-positive ankylosing spondylitis-related uveitis. Am J Ophthalmol. 170:32–40. DOI: 10.1016/j.ajo.2016.07.016. PMID: 27470062.
crossref
113. Gao X, Wendling D, Botteman MF, Carter JA, Rao S, Cifaldi M. 2012; Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents. J Med Econ. 15:1054–63. DOI: 10.3111/13696998.2012.692341. PMID: 22563743.
crossref
114. Braun J, Baraliakos X, Listing J, Sieper J. 2005; Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 52:2447–51. DOI: 10.1002/art.21197. PMID: 16052578.
crossref
115. Braun J, Baraliakos X, Listing J, Davis J, van der Heijde D, Haibel H, et al. 2007; Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum. 57:639–47. DOI: 10.1002/art.22669. PMID: 17471540.
crossref
116. Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M, Duclos M, et al. 2006; Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis. 65:1631–4. DOI: 10.1136/ard.2006.052092. PMID: 16901960. PMCID: PMC1798480.
crossref
117. Koo BS, Hong S, Kim YJ, Lee CK, Yoo B, Kim YG. 2015; The incidence of uveitis in ankylosing spondylitis patients undergoing tumor necrosis factor inhibiting therapy in Korea. J Rheum Dis. 22:288–92. DOI: 10.4078/jrd.2015.22.5.288.
crossref
118. Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, et al. 2012; Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 61:1693–700. DOI: 10.1136/gutjnl-2011-301668. PMID: 22595313. PMCID: PMC4902107.
crossref
119. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. 2015; Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 373:2534–48. DOI: 10.1056/NEJMoa1505066. PMID: 26699169.
crossref
120. van der Heijde D, Cheng-Chung Wei J, Dougados M, Mease P, Deodhar A, Maksymowych WP, et al. 2018; Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 392:2441–51. DOI: 10.1016/S0140-6736(18)31946-9. PMID: 30360964.
121. Kivitz AJ, Wagner U, Dokoupilova E, Supronik J, Martin R, Talloczy Z, et al. 2018; Efficacy and safety of secukinumab 150 mg with and without loading regimen in ankylosing spondylitis: 104-week results from MEASURE 4 study. Rheumatol Ther. 5:447–62. DOI: 10.1007/s40744-018-0123-5. PMID: 30121827. PMCID: PMC6251842.
crossref
122. Huang F, Sun F, Wan WG, Wu LJ, Dong LL, Zhang X, et al. 2020; Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week, Phase III China-centric study, MEASURE 5. Chin Med J (Engl). 133:2521–31. DOI: 10.1097/CM9.0000000000001099. PMID: 32925287. PMCID: PMC7722578.
crossref
123. Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, et al. 2020; Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 395:53–64. DOI: 10.1016/S0140-6736(19)32971-X. PMID: 31813637.
124. Deodhar A, Blanco R, Dokoupilová E, Hall S, Kameda H, Kivitz AJ, et al. 2021; Improvement of signs and symptoms of nonradiographic axial spondyloarthritis in patients treated with secukinumab: primary results of a randomized, placebo-controlled phase III study. Arthritis Rheumatol. 73:110–20. DOI: 10.1002/art.41477. PMID: 32770640. PMCID: PMC7839589.
crossref
125. Baraliakos X, Gossec L, Pournara E, Jeka S, Mera-Varela A, D'Angelo S, et al. 2021; Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial. Ann Rheum Dis. 80:582–90. DOI: 10.1136/annrheumdis-2020-218808. PMID: 33334727. PMCID: PMC8053347.
crossref
126. Ten Bergen LL, Petrovic A, Krogh Aarebrot A, Appel S. 2020; The TNF/IL-23/IL-17 axis-Head-to-head trials comparing different biologics in psoriasis treatment. Scand J Immunol. 92:e12946. DOI: 10.1111/sji.12946.
crossref
127. Gossec L, Baraliakos X, Kerschbaumer A, de Wit M, McInnes I, Dougados M, et al. 2020; EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis. 79:700–12. DOI: 10.1136/annrheumdis-2020-217159. PMID: 32434812.
128. Ciurea A, Exer P, Weber U, Tamborrini G, Steininger B, Kissling RO, et al. 2016; Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort. Arthritis Res Ther. 18:71. DOI: 10.1186/s13075-016-0969-2. PMID: 27000865. PMCID: PMC4802885.
crossref
129. Rudwaleit M, Van den Bosch F, Kron M, Kary S, Kupper H. 2010; Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res Ther. 12:R117. DOI: 10.1186/ar3054. PMID: 20553600. PMCID: PMC2911911.
crossref
130. Lie E, van der Heijde D, Uhlig T, Mikkelsen K, Rødevand E, Koldingsnes W, et al. 2011; Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register. Ann Rheum Dis. 70:157–63. DOI: 10.1136/ard.2010.131797. PMID: 21062852.
crossref
131. Manica SR, Sepriano A, Pimentel-Santos F, Gouveia N, Barcelos A, Branco JC, et al. 2020; Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant? Arthritis Res Ther. 22:195. DOI: 10.1186/s13075-020-02288-8. PMID: 32825839. PMCID: PMC7441644.
crossref
132. Paccou J, Solau-Gervais E, Houvenagel E, Salleron J, Luraschi H, Philippe P, et al. 2011; Efficacy in current practice of switching between anti-tumour necrosis factor- α agents in spondyloarthropathies. Rheumatology (Oxford). 50:714–20. DOI: 10.1093/rheumatology/keq377. PMID: 21131271.
133. Deodhar A, Yu D. 2017; Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis. Semin Arthritis Rheum. 47:343–50. DOI: 10.1016/j.semarthrit.2017.04.005. PMID: 28551170.
crossref
134. Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler LS, Fleishaker D, et al. 2021; Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 80:1004–13. DOI: 10.1136/annrheumdis-2020-219601. PMID: 33906853. PMCID: PMC8292568.
crossref
135. van der Heijde D, Song IH, Pangan AL, Deodhar A, van den Bosch F, Maksymowych WP, et al. 2019; Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 394:2108–17. DOI: 10.1016/S0140-6736(19)32534-6. PMID: 31732180.
crossref
136. van der Heijde D, Deodhar A, Wei JC, Drescher E, Fleishaker D, Hendrikx T, et al. 2017; Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 76:1340–7. DOI: 10.1136/annrheumdis-2016-210322. PMID: 28130206. PMCID: PMC5738601.
crossref
137. Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, et al. 2016; Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis. 75:1438–43. DOI: 10.1136/annrheumdis-2015-207897. PMID: 26242443.
crossref
138. Wanders A, Landewé R, Béhier JM, Calin A, Olivieri I, et al. Heijde Dv. 2005; Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 52:1756–65. DOI: 10.1002/art.21054. PMID: 15934081.
crossref
139. Committee for Medicinal Products for Human Use. c2014. Guideline on similar biological medicinal products [Internet]. European Medicines Agency;London: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf. cited 2023 Apr 18.
140. US Food and Drug Administration. c2015. Scientific considerations in demonstrating biosimilarity to a reference product: guidance for industry [Internet]. US Food and Drug Administration;Silver Spring (MD): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/scientific-considerations-demonstrating-biosimilarity-reference-product. cited 2023 Apr 18.
141. Smolen JS, Goncalves J, Quinn M, Benedetti F, Lee JY. 2019; Era of biosimilars in rheumatology: reshaping the healthcare environment. RMD Open. 5:e000900. DOI: 10.1136/rmdopen-2019-000900. PMID: 31245050. PMCID: PMC6560670.
crossref
142. Su J, Li M, He L, Zhao D, Wan W, Liu Y, et al. 2020; Comparison of the efficacy and safety of adalimumab (Humira) and the adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis: a multicenter, randomized, double-blind, parallel, phase III clinical trial. BioDrugs. 34:381–93. DOI: 10.1007/s40259-020-00408-z. PMID: 32078145. PMCID: PMC7211209.
crossref
143. Xu H, Li Z, Wu J, Xing Q, Shi G, Li J, et al. 2019; IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: a randomised, double-blind, phase 3 equivalence trial. Lancet Rheumatol. 1:e35–43. DOI: 10.1016/S2665-9913(19)30013-X.
crossref
144. Park W, Yoo DH, Jaworski J, Brzezicki J, Gnylorybov A, Kadinov V, et al. 2016; Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study. Arthritis Res Ther. 18:25. DOI: 10.1186/s13075-016-0930-4. PMID: 26795209. PMCID: PMC4721187.
crossref
145. Landewé RB, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch FE, Gaffney K, et al. 2020; Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 79:920–8. Erratum. DOI: 10.1136/annrheumdis-2019-216839. PMID: 32381562. PMCID: PMC7307216.
crossref
146. Landewé R, Sieper J, Mease P, Inman RD, Lambert RG, Deodhar A, et al. 2018; Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 392:134–44. DOI: 10.1016/S0140-6736(18)31362-X. PMID: 29961640.
crossref
147. Gratacós J, Pontes C, Juanola X, Sanz J, Torres F, Avendaño C, et al. 2019; Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Ther. 21:11. DOI: 10.1186/s13075-018-1772-z. PMID: 30621746. PMCID: PMC6323809.
crossref
148. Cantini F, Niccoli L, Cassarà E, Kaloudi O, Nannini C. 2013; Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study. Biologics. 7:1–6. DOI: 10.2147/BTT.S31474. PMID: 23319853. PMCID: PMC3540908.
crossref
149. Fernández-Carballido C, Collantes-Estévez E, Gratacós J, Juanola X, Zarco P. 2021; Remission in axial spondyloarthritis: developing a consensus definition. Reumatol Clin (Engl Ed). 17:380–7. DOI: 10.1016/j.reuma.2020.01.003. PMID: 34301380.
crossref
150. Chang JK, Yu CT, Lee MY, Yeo K, Chang IC, Tsou HK, et al. 2013; Tramadol/acetaminophen combination as add-on therapy in the treatment of patients with ankylosing spondylitis. Clin Rheumatol. 32:341–7. DOI: 10.1007/s10067-012-2125-y. PMID: 23192419.
crossref
151. Gurcay E, Yuzer S, Eksioglu E, Bal A, Cakci A. 2008; Stanger bath therapy for ankylosing spondylitis: illusion or reality? Clin Rheumatol. 27:913–7. DOI: 10.1007/s10067-008-0873-5. PMID: 18357500.
crossref
152. van Tubergen A, Landewé R, van der Heijde D, Hidding A, Wolter N, Asscher M, et al. 2001; Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Rheum. 45:430–8. DOI: 10.1002/1529-0131(200110)45:5<430::AID-ART362>3.0.CO;2-F. PMID: 11642642.
crossref
153. Jo JH, Kweon JJ, Song YK, Lim HH, Beak HJ. 2012; Acupuncture's efficacy and safety in axial spondyloarthritis within 4 weeks session: a randomized, double-blind, sham-controlled trial. J Orient Rehabil Med. 22:23–36.
154. Vander Cruyssen B, Muñoz-Gomariz E, Font P, Mulero J, de Vlam K, Boonen A, et al. 2010; Hip involvement in ankylosing spondylitis: epidemiology and risk factors associated with hip replacement surgery. Rheumatology (Oxford). 49:73–81. DOI: 10.1093/rheumatology/kep174. PMID: 19605374.
crossref
155. Jeong H, Eun YH, Kim IY, Kim H, Lee J, Koh EM, et al. 2017; Characteristics of hip involvement in patients with ankylosing spondylitis in Korea. Korean J Intern Med. 32:158–64. DOI: 10.3904/kjim.2015.229. PMID: 27017388. PMCID: PMC5214726.
crossref
156. Yoo MC, Chung DW, Kim JJ, Lee HK. 1994; Total hip replacement in the ankylosing spondylitis. J Korean Rheum Assoc. 1:23–32.
157. Joshi AB, Markovic L, Hardinge K, Murphy JC. 2002; Total hip arthroplasty in ankylosing spondylitis: an analysis of 181 hips. J Arthroplasty. 17:427–33. DOI: 10.1054/arth.2002.32170. PMID: 12066271.
crossref
158. Li J, Xu W, Xu L, Liang Z. 2009; Hip resurfacing arthroplasty for ankylosing spondylitis. J Arthroplasty. 24:1285–91. DOI: 10.1016/j.arth.2009.07.003. PMID: 19682837.
crossref
159. Lee SH, Lee GW, Seol YJ, Park KS, Yoon TR. 2017; Comparison of outcomes of total hip arthroplasty between patients with ankylosing spondylitis and avascular necrosis of the femoral head. Clin Orthop Surg. 9:263–9. DOI: 10.4055/cios.2017.9.3.263. PMID: 28861192. PMCID: PMC5567020.
crossref
160. Lin D, Charalambous A, Hanna SA. 2019; Bilateral total hip arthroplasty in ankylosing spondylitis: a systematic review. EFORT Open Rev. 4:476–81. DOI: 10.1302/2058-5241.4.180047. PMID: 31423331. PMCID: PMC6667978.
crossref
161. Sambrook PN, Geusens P. 2012; The epidemiology of osteoporosis and fractures in ankylosing spondylitis. Ther Adv Musculoskelet Dis. 4:287–92. DOI: 10.1177/1759720X12441276. PMID: 22859927. PMCID: PMC3403252.
crossref
162. Vosse D, Lems WF, Geusens PP. 2013; Spinal fractures in ankylosing spondylitis: prevalence, prevention and management. Int J Clin Rheumatol. 8:597–608. DOI: 10.2217/ijr.13.37.
crossref
163. Ognjenovic M, Raymond WD, Inderjeeth CA, Keen HI, Preen DB, Nossent JC. 2020; The risk and consequences of vertebral fracture in patients with ankylosing spondylitis: a population-based data linkage study. J Rheumatol. 47:1629–36. DOI: 10.3899/jrheum.190675. PMID: 32062601.
crossref
164. Westerveld LA, Verlaan JJ, Oner FC. 2009; Spinal fractures in patients with ankylosing spinal disorders: a systematic review of the literature on treatment, neurological status and complications. Eur Spine J. 18:145–56. DOI: 10.1007/s00586-008-0764-0. PMID: 18791749. PMCID: PMC2899332.
crossref
165. Tu PH, Liu ZH, Yeap MC, Liu YT, Li YC, Huang YC, et al. 2022; Spinal cord injury and spinal fracture in patients with ankylosing spondylitis. BMC Emerg Med. 22:73. DOI: 10.1186/s12873-022-00635-3. PMID: 35501709. PMCID: PMC9063196.
crossref
166. Kandregula S, Birk HS, Savardekar A, Newman WC, Beyl R, Trosclair K, et al. 2021; Spinal fractures in ankylosing spondylitis: patterns, management, and complications in the United States - analysis of latest Nationwide Inpatient Sample data. Neurospine. 18:786–97. DOI: 10.14245/ns.2142712.356. PMID: 35000333. PMCID: PMC8752689.
crossref
167. Werner BC, Samartzis D, Shen FH. 2016; Spinal fractures in patients with ankylosing spondylitis: etiology, diagnosis, and management. J Am Acad Orthop Surg. 24:241–9. DOI: 10.5435/JAAOS-D-14-00149. PMID: 26890162.
168. Reinhold M, Knop C, Kneitz C, Disch A. 2018; Spine fractures in ankylosing diseases: recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU). Global Spine J. 8(2 Suppl):56S–68S. DOI: 10.1177/2192568217736268. PMID: 30210963. PMCID: PMC6130102.
crossref
169. Rustagi T, Drazin D, Oner C, York J, Schroeder GD, Vaccaro AR, et al. 2017; Fractures in spinal ankylosing disorders: a narrative review of disease and injury types, treatment techniques, and outcomes. J Orthop Trauma. 31 Suppl 4:S57–74. DOI: 10.1097/BOT.0000000000000953. PMID: 28816877.
crossref
170. Lauper K, Courvoisier DS, Chevallier P, Finckh A, Gabay C. 2018; Incidence and prevalence of major adverse cardiovascular events in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. Arthritis Care Res (Hoboken). 70:1756–63. DOI: 10.1002/acr.23567. PMID: 29609199.
crossref
171. Zhao SS, Robertson S, Reich T, Harrison NL, Moots RJ, Goodson NJ. 2020; Prevalence and impact of comorbidities in axial spondyloarthritis: systematic review and meta-analysis. Rheumatology (Oxford). 59(Suppl4):iv47–57. DOI: 10.1093/rheumatology/keaa246. PMID: 33053193. PMCID: PMC7566561.
crossref
172. Wang JK, Park US, Lee HS, Uhm WS, Kim TH, Bae SC, et al. 2004; The clinical significance of bone mineral density measurement in patients with ankylosing spondylitis. J Korean Rheum Assoc. 11:342–8.
173. Toussirot E, Michel F, Wendling D. 2001; Bone density, ultrasound measurements and body composition in early ankylosing spondylitis. Rheumatology (Oxford). 40:882–8. DOI: 10.1093/rheumatology/40.8.882. PMID: 11511757.
crossref
174. Magrey MN, Lewis S, Asim Khan M. 2016; Utility of DXA scanning and risk factors for osteoporosis in ankylosing spondylitis-a prospective study. Semin Arthritis Rheum. 46:88–94. DOI: 10.1016/j.semarthrit.2016.03.003. PMID: 27162010.
crossref
175. Karberg K, Zochling J, Sieper J, Felsenberg D, Braun J. 2005; Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol. 32:1290–8.
176. Guidelines for monitoring drug therapy in rheumatoid arthritis. 1996; American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum. 39:723–31. DOI: 10.1002/art.1780390503.

Fig. 1
Treatment algorithm based on Korean treatment recommendations for patients with axial spondyloarthritis. GC: glucocorticoid, IBD: inflammatory bowel disease, IL-17: interleukin-17, JAK: Janus kinase, NSAID: non-steroidal anti-inflammatory drug, SSZ: sulfasalazine, TNF: tumor necrosis factor.
jrd-30-3-151-f1.tif
Table 1
Definitions of grade of evidence and strength of recommendation
Grade of evidence*
High We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of the effect.
Strength of recommendation†
Strong If the panel is highly confident of the balance between desirable and undesirable consequences, they make a strong recommendation for (desirable outweighs undesirable) or against (undesirable outweighs desirable) an intervention.
Weak If the panel is less confident of the balance between desirable and undesirable consequences, they offer a weak recommendation.
Table 2
Korean treatment recommendations for patients with axial spondyloarthritis (axSpA)*
GoE SoR LoA (1~5)
Overarching principles
1. axSpA is a potentially disabling inflammatory disease of the spine, often associated with articular, periarticular, or non-articular features. Strong 100% (≥4)
2. The primary goal of management in axSpA is to maximize patients’ health-related QoL through control of symptoms and inflammation, prevention of structural damage, minimization of non-articular manifestations, and maintenance of function. Strong 100% (≥4)
3. Treatment of axSpA should be based on shared decisions between the patient and physician, which usually requires multidisciplinary management coordinated by the rheumatologist. Strong 100% (≥4)
Recommendations
Treatment strategies
1. We recommend that the treatment of axSpA should be tailored for each patient using regular assessments of their clinical state and disease activity. Very low Strong 100% (≥4)
2. We recommend collaboration with a relevant specialist for the diagnosis and treatment of extraarticular symptoms. Very low Strong 100% (≥4)
Non-pharmacological and non-surgical management
3. We recommend that education about axSpA should be provided to all patients. Moderate Strong 100% (≥4)
4. We recommend smoking cessation and regular exercise. Low Strong 96.8% (≥4)
Pharmacological treatment in active disease
5. In patients with active axSpA, we recommend that treatment with a full-dose NSAID should be initiated. High Strong 96.8% (≥4)
6. In patients with active axSpA resistant to NSAIDs therapy, we suggest that systemic glucocorticoids not be used, but local glucocorticoid injections be considered for active peripheral arthritis or isolated sacroiliitis. Very low Weak 90.3% (≥4)
7. In axSpA patients with active peripheral arthritis resistant to NSAIDs therapy, we suggest that an additional SSZ be considered when biologic therapy is restricted by regulatory guidelines or not preferred by the patient. Moderate Weak 96.8% (≥4)
8. In patients with active axSpA resistant to NSAID therapy, we recommend treating with TNF inhibitors. High Strong 100% (≥4)
9. In patients with active axSpA resistant to NSAID therapy who have uveitis or IBD, we suggest treatment with monoclonal TNF inhibitors as initial biological agents. Low Weak 100% (≥4)
10. In patients with active axSpA resistant to NSAID therapy who have significant psoriasis, we suggest consideration of IL-17 inhibitors as an alternative biologic therapy. High Weak 96.8% (≥4)
11. In patients with active axSpA resistant to a TNF inhibitor, we recommend switching to a different TNF inhibitor or to an IL-17 inhibitor. Low Strong 100% (≥4)
12. In patients with active axSpA despite biologic therapy, JAK inhibitor use can be considered. Very low Weak 80.6% (≥4)
Pharmacological treatment in stable disease
13. In patients with stable axSpA, we suggest treatment with on-demand NSAIDs rather than continuous NSAIDs. Low Weak 83.9% (≥4)
14. In patients with stable axSpA, we suggest that biologic originators be replaced with biosimilars. Moderate Weak 83.9% (≥4)
15. In patients with axSpA in long-term remission, we suggest consideration of tapering of biologic therapy. Moderate Weak 96.8% (≥4)
16. We suggest the addition of analgesics to control residual pain. Low Weak 87.1% (≥4)
Complementary medicine
17. We suggest that spa and acupuncture not be provided to patients with axSpA as therapies. Low Weak 80.6% (≥4)
Surgical treatment
18. We recommend that total hip arthroplasty should be considered for patients with refractory pain or disability caused by radiographic hip destruction. Very low Strong 96.8% (≥4)
19. We suggest consideration of spinal surgery for acute spinal fracture in patients with axSpA. Very low Weak 83.9% (≥4)
Monitoring of comorbidities and drug toxicities
20. We suggest monitoring and treating comorbidities such as cardiovascular disease and osteoporosis in patients with axSpA. Very low Weak 100% (≥4)
21. We recommend that drug toxicities should be monitored in patients with axSpA on pharmacological therapy. Very low Strong 90.3% (≥4)
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