The Incidence of Uveitis in Ankylosing Spondylitis Patients Undergoing Tumor Necrosis Factor Inhibiting Therapy in Korea

Bon San Koo; Seokchan Hong; You Jae Kim; Chang-Keun Lee; Bin Yoo; Yong-Gil Kim

doi:10.4078/jrd.2015.22.5.288

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Koo, Hong, Kim, Lee, Yoo, and Kim: The Incidence of Uveitis in Ankylosing Spondylitis Patients Undergoing Tumor Necrosis Factor Inhibiting Therapy in Korea

Original Article

J Rheum Dis 2015;22(5):288-292.

Published online: 31 October 2015

DOI: https://doi.org/10.4078/jrd.2015.22.5.288

The Incidence of Uveitis in Ankylosing Spondylitis Patients Undergoing Tumor Necrosis Factor Inhibiting Therapy in Korea

Bon San Koo^1,^*, Seokchan Hong^2,^*, You Jae Kim², Chang-Keun Lee², Bin Yoo², Yong-Gil Kim²

¹Division of Rheumatology, Department of Internal Medicine, Konkuk University Chungju Hospital, Konkuk University College of Medicine, Chungju, Korea

²Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding to: Yong-Gil Kim, Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: bestmd2000@amc.seoul.kr *The first two authors contributed equally to this work.

^* The first two authors contributed equally to this work.

Received 12 March 2015 Revised 4 June 2015 Accepted 5 June 2015

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

Abstract

Objective

The purpose of this study is to evaluate the outcome of uveitis in ankylosing spondylitis (AS) during tumor necrosis factor (TNF)-inhibiting therapy and to compare the incidence rate of uveitis in infliximab, adalimumab, and etanercept.

Methods

A retrospective evaluation was performed in AS patients who had started TNF-inhibiting therapy from June 2003 to June 2011. The clinical characteristics of patients with documented uveitis were evaluated.

Results

Among 316 patients treated with TNF inhibitor, 26 patients (8%) had experienced uveitis during TNF-inhibiting therapy. Among them, 15 patients were treated with etanercept, eight with adalimumab, and three with infliximab. The overall incidence rate of uveitis flare during therapy with TNF inhibitor was 46 per 1,000 person-years (pys) (95% confidence interval [CI], 32 to 64). The incidence rate did not differ between TNF inhibitors, with 54/1,000 pys (95% CI, 34 to 81) for etanercept, 46/1,000 pys (95% CI, 21 to 87) for adalimumab, and 22/1,000 pys (95% CI, 5 to 64) for infliximab. Fourteen patients experienced a first episode of uveitis. The overall incidence rate of new onset-uveitis after therapy with TNF inhibitor was 19 per 1,000 pys (95% CI, 10 to 31). The incidence rate for etanercept was 24/1,000 pys (95% CI, 12 to 45); adalimumab, 15/1,000 pys (95% CI, 3 to 45); and infliximab, 7/1,000 pys (95% CI, 0 to 40). There was no statistical difference in the incidence of uveitis flare or the cumulative uveitis-free rate among the three TNF inhibitors.

Conclusion

The relative rate of uveitis, including the first episode, was determined using the TNF inhibitor. However, there was no difference in the incidence rate of uveitis among the three TNF inhibitors.

Keywords: Tumor necrosis factor, Ankylosing spondylitis, Uveitis

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Figure 1.

Cumulative uveitis-free survival rate after tumor necrosis fator (TNF) inhibitors (A) in all patients and (B) in patients who had never experienced uveitis before TNF-inhibiting therapy.

Table 1.

Comparison of the clinical characteristics of AS patients treated with infliximab, adalimumab, or etanercept

Characteristic	Total†(n=316)	Infliximab (n=85)	Adalimumab (n=148)	Etanercept (n=142)	p-value
Age at the start of TNFi (yr)	36.1±11.8	36.4±11.6	36.3±11.6	36.4±12.4	0.987
Male (%)	81	77	74	83	0.189
HLA-B27 positivity (%)	95	95	94	95	0.901
AS disease duration (mo)	75.7±52.9	86.1±54.8	58.63±50.1	86.8±51.1	0.000
Duration of TNFi exposure (mo)	23.9±19.4	19.5±15.0	16.1±12.5	34.6±22.6	0.001
Body mass index (kg/m²)	24.2±3.9	23.9±3.5	24.5±4.3	24.1±4.0	0.598
Previous history of uveitis	42 (13)	6 (7)	21 (14)	15 (11)	0.252
Uveitis during TNFi therapy	26 (8)	3 (4)	8 (5)	15 (11)	0.000
Uveitis during TNFi therapy (episode)	34 (11)	3 (4)	9 (6)	22 (15)	0.004
Incidence rate of uveitis during TNFi therapy (per 1,000 pys)	46 (32∼64)	22 (5∼64)	46 (21∼87)	54 (34∼81)	0.257*
New onset of uveitis during TNFi therapy	14 (4)	1 (1)	3 (2)	10 (7)	0.029
Incidence rate of new onset of uveitis during TNFi therapy (per 1,000 pys)	19 (10∼31)	7 (0∼40)	15 (3∼45)	24 (12∼45)	0.357*

Values are presented as mean±standard deviation, percent only, number (%), or median (95% CI). AS: ankylosing spondylitis, HLA: human leukocyte antigen, TNFi: tumor necrosis factor inhibitor, CI: confidence interval, pys: person-years.

^* Using Poisson regression;

^† including 59 patients who were treated with second or third TNFi.

Table 2.

Cox proportional hazard analysis for uveitis of ankylosing spondylitis patients treated with infliximab, adalimumab, or etanercept

Characteristic	Infliximab (n=85)	Adalimumab (n=148)		Etanercept (n=142)
Characteristic	Infliximab (n=85)	95% CI	p	95% CI	p
HR developing uveitis during TNFi therapy	Reference	2.0 (0.5∼7.8)	0.295	1.6 (0.5∼5.8)	0.461
Adjusted HR developing uveitis during TNFi	Reference	1.8 (0.4∼7.9)	0.429	1.7 (0.4∼6.5)	0.443
therapy*
HR of new onset of uveitis	Reference	2.8 (0.3∼28.2)	0.37	2.8 (0.3∼22.7)	0.336
Adjusted HR of new onset of uveitis*	Reference	0.9 (0.1∼12.3)	0.98	3.1 (0.3∼27.0)	0.312

CI: confidence interval, HR: hazard ratio, TNFi: tumor necrosis factor inhibitor.

^* Adjusted for ankylosing spondylitis disease duration and duration of TNFi exposure.

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