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Cho, Kim, Park, Choi, Choi, Jung, Jang, and Sung: Nonsteroidal Anti-inflammatory Drugs-sparing Effect of Symptomatic Slow-acting Drugs for Osteoarthritis in Knee Osteoarthritis Patients
Original Article

J Rheum Dis 2019;26(3):179-185.

Published online: 31 October 2019

DOI: https://doi.org/10.4078/jrd.2019.26.3.179

Nonsteroidal Anti-inflammatory Drugs-sparing Effect of Symptomatic Slow-acting Drugs for Osteoarthritis in Knee Osteoarthritis Patients

Soo-Kyung Cho1, Hyoungyoung Kim1, Ha-Rim Park1, Wooseok Choi2, Seongmi Choi2, Sun-Young Jung3, Eun Jin Jang4, Yoon-Kyoung Sung1

1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

2Department of Statistics, Kyungpook National University, Daegu, Korea

3College of Pharmacy, Chung-Ang University, Seoul, Korea

4Department of Information Statistics, Andong National University, Andong, Korea

Corresponding to: Yoon-Kyoung Sung http://orcid.org/0000-0001-6691-8939 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. E-mail: sungyk@hanyang.ac.kr

Received 26 December 201813 March 2019       Accepted 13 March 2019

Copyright © 2019 The Korean College of Rheumatology

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To evaluate the nonsteroidal anti-inflammatory drugs (NSAID)-sparing effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) in knee osteoarthritis (OA) patients.

Methods

A retrospective study was conducted on a cohort of knee OA patients who visited a single academic referral hospital from 2013 to 2014. Among all patients, NSAID users in their first visit were extracted and divided into SYSADOA users and SYSADOA non-users. All patients were observed from their first visit with knee OA to their last visit, NSAID discontinuation, or the date of data collection, July 2017 (mean observational periods: 369.1 days). To evaluate the NSAID-sparing effect of SYSADOA, Cox regression analysis was performed after adjusting for confounding factors.

Results

Patients for this study (n=212) were divided into SYSADOA users (n=57) and SYSADOA non-users (n=155). The mean age (68.8 vs. 66.6 years old, p=0.31) and the number of comorbidities (p=0.73) were comparable between the two groups. The SYSADOA users showed higher Kellgren– Lawrence (KL) grade (66.7% of patients with more than KL grade 3) than SYSADOA non-users (42.6% of patients with more than KL grade 3) (p=0.02). In treatment, the frequency of intraarticular injection was higher in the SYSADOA user group than the SYSADOA non-user group (33.3% vs. 9.0%, p<0.01). In Cox regression analysis, SYSADOA use contributed to NSAID discontinuation in knee OA patients (hazard ratio 2.97, 95% confidential interval 1.42∼6.22).

Conclusion

This real-world analysis demonstrated that SYSADOA use combined with NSAIDs had a significant effect on NSAID discontinuation in patients with knee OA.

Keywords: Osteoarthritis, Symptomatic slow-acting drugs for osteoarthritis, Nonsteroidal anti-inflammatory drugs

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Table 1.
Baseline and clinical characteristics of study population
Variable Total (n=212) SYSADOA users (n=57) SYSADOA non-users (n=155) p-value
Age (yr) 67.9±7.7 68.8±8.0 66.6±7.6 0.31
Sex (female) 184 (86.8) 48 (84.2) 136 (87.7) 0.50
Outpatient visits 199 (93.9) 56 (98.3) 143 (92.3) 0.19
 Rheumatology 123 (58.0) 32 (56.1) 91 (58.7) <0.01
 Orthopedic surgery 65 (30.7) 6 (10.5) 59 (38.1) 0.74
 Rehabilitation 44 (20.8) 27 (47.4) 17 (11.0) <0.01
 Cardiology 16 (7.6) 2 (3.5) 14 (9.0) 0.25
 Gastroenterology 3 (1.4) 0 3 (1.9) 0.57
 General surgery 1 (0.5) 0 1 (0.7) 1.00
Previous history of chronic diseases
 Hypertension 67 (32.9) 16 (28.1) 51 (32.9) 0.50
 Diabetes mellitus 27 (13.5) 6 (10.5) 21 (13.5) 0.56
 Chronic kidney disease* 58 (27.4) 16 (28.1) 42 (27.1) 0.89
 Gastrointestinal disease 5 (2.4) 0 5 (3.2) 0.33
Number of comorbidities†
 0 199 (93.9) 53 (93.0) 146 (94.2) 0.73
 1 9 (4.3) 3 (5.3) 6 (3.9)
 ≥2 4 (1.9) 1 (1.8) 3 (1.9)
Knee X-ray KL grade at first visit
 KL grade 1 42 (19.8) 10 (17.5) 32 (20.7) 0.02
 KL grade 2 57 (26.9) 9 (15.8) 48 (31.0)
 KL grade 3 100 (47.2) 36 (63.2) 64 (41.3)
 KL grade 4 4 (1.9) 2 (3.5) 2 (1.3)

Values are presented as mean±standard deviation or number (%). SYSADOA: symptomatic slow-acting drugs for osteoarthritis, KL grade: Kellgren–Lawrence grade.

* Chronic kidney diseases were defined by <60 mL/min/1.73 m2 of glomerular filtration rate.

† Comorbidities were identified using the Charlson comorbidity index.

Table 2.
Comparison of treatment patterns in SYSADOA users and SYSADOA non-users during the observation period
Variable Total (n=212) SYSADOA users (n=57) SYSADOA non-users (n=155) p-value
Analgesics 132 (62.3) 41 (71.9) 91 (58.7) 0.08
Corticosteroids 22 (10.4) 4 (7.0) 13 (11.6) 0.33
GI protect med 170 (80.2) 47 (82.5) 123 (79.4) 0.62
 Proton pump inhibitor 50 (23.6) 10 (17.5) 40 (25.8) 0.21
 H2 blocker 11 (5.2) 3 (5.3) 8 (5.2) 1.00
 Rebamipide 1 (0.5) 0 (0) 1 (0.6) 1.00
 Sucralfate 40 (18.9) 13 (22.8) 27 (17.4) 0.37
 Artemisia asiatica 7 (3.3) 2 (3.5) 5 (3.2) 1.00
 Teprenone 11 (5.2) 3 (5.3) 8 (5.2) 1.00
 Others 123 (58) 35 (61.4) 88 (56.8) 0.54
Intra-articular injection 33 (15.6) 19 (33.3) 14 (9.0) <0.01
 Corticosteroids injection 9 (4.2) 4 (7.0) 5 (3.2) 0.25
 Hyaluronic acid injection 24 (11.3) 15 (26.3) 9 (5.8) <0.01
Total knee replacement 16 (7.5) 3 (5.3) 13 (8.4) 0.45

Values are presented as number (%). SYSADOA: symptomatic slow acting drugs for osteoarthritis, GI: gastrointestinal.

Table 3.
Factors influencing on NSAID discontinuation
Variable Unadjusted Adjusted
 HR (95% CI) p-value HR (95% CI) p-value
Age 1.00 (0.97∼1.04) 0.80 0.97 (0.92∼1.01) 0.14
Sex 0.96 (0.34∼2.68) 0.93 0.94 (0.33∼2.67) 0.91
Comorbidities
 Gastrointestinal disease 2.26 (0.54∼9.39) 0.26 4.74 (1.06∼21.27) 0.04
 Cardiovascular disease 0.92 (0.50∼1.72) 0.80
 Diabetes mellitus 0.56 (0.17∼1.80) 0.33
 Chronic kidney disease* 1.59 (0.74∼3.42) 0.24 1.22 (0.35∼4.31) 0.76
Number of comorbidities 0.77 (0.35∼1.69) 0.51
KL grade 1.64 (1.15∼2.35) 0.01 1.39 (0.92∼2.11) 0.12
IAI with corticosteroid 0.63 (0.15∼2.59) 0.52
IAI with hyaluronic acid 1.36 (0.58∼3.23) 0.48
TKR 4.13 (2.12∼8.04) <0.01 6.21 (2.66∼14.49) <0.01
Medication†
 SYSADOA 1.90 (1.02∼3.54) 0.04 2.97 (1.42∼6.22) <0.01
 Analgesics 2.16 (1.18∼3.94) 0.01 1.43 (0.75∼2.71) 0.28
 Corticosteroids 0.33 (0.05∼2.40) 0.27 0.32 (0.04∼2.36) 0.26

NSAIDs: nonsteroidal anti-inflammatory drugs, HR: hazard ratio, CI: confidence interval, KL grade: Kellgren– Lawrence grade, IAI: intraarticular injection, TKR: total knee replacement, SYSADOA: symptomatic slow-acting drugs for osteoarthritis.

* Chronic kidney diseases were defined by <60 mL/min/1.73 m2 of glomerular filtration rate.

† Medication during the observational period was used by time dependent variables.

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