335 Received：November 13, 2015, Accepted：November 16, 2015
Corresponding to：Sung Jae Choi, Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. E-mail：[email protected]
pISSN: 2093-940X, eISSN: 2233-4718
Copyright ⓒ 2015 by The Korean College of Rheumatology. All rights reserved.
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.
Editorial
Journal of Rheumatic Diseases Vol. 22, No. 6, December, 2015 http://dx.doi.org/10.4078/jrd.2015.22.6.335
The Incidence of Uveitis in Ankylosing Spondylitis Patients Undergoing Tumor Necrosis Factor Inhibiting Therapy in Korea
Sung Jae Choi
Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
Ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease that primarily affects the sacroiliac joints and causes inflammatory back pain, is often accom- panied by inflammatory extra-articular manifestations such as Crohn’s disease, psoriasis, and uveitis [1]. In a systematic literature review of extra-articular manifes- tations in patients with AS, acute anterior uveitis (26%) was more common than psoriasis (9%) or inflammatory bowel disease (7%) [2]. Other studies have estimated that 25% to 50% of patients experience at least one epi- sode of uveitis during the course of AS. Characteristics of uveitis in patients with AS include predominantly acute, unilateral onset; anterior location; strong association with human leukocyte antigen (HLA)-B27 positivity; and tendency to recur, often in the opposite eye. In addition, the incidence of uveitis increases with longer disease du- ration, ranging from 17% for patients with disease dura- tion ＜10 years to 39% for patients with disease duration
＞20 years [2].
Uveitis is a painful, often recurrent, and potentially seri- ous inflammation of the eye. It is the most preventable cause of blindness worldwide and also has a negative ef- fect on health-related quality of life. AS patients with ex- traarticular manifestations utilize more medical re- sources and incur more health care costs compared with AS patients who do not develop extra-articular mani- festations. Complications of inadequately treated uveitis include cataract formation, glaucoma, and maculopathy, all of which can lead to visual acuity loss and ultimately blindness. In patients with spondyloarthropathies, uvei-
tis was associated with reduced visual acuity in 8% of pa- tients; and approximately 50% of patients had at least one recurrent flare [3].
Tumor necrosis factor (TNF) is involved in the patho- genesis of both uveitis and AS. TNF is elevated in the aqueous humor and serum of patients affected by uveitis and the joints of patients with AS. Anti-TNF therapy has been shown to reduce ocular inflammation and preserve vision in patients with sight-threatening uveitis, and there is considerable interest in the use of biologic treat- ments for uveitis and other ocular inflammatory disorders.
The anti-TNF agents adalimumab and infliximab have been shown to reduce uveitis flares in patients with AS [4,5], whereas evidence for the ability of etanercept to prevent uveitis flares is mixed [5,6]. Conversely, uveitis develops in some patients, whose articular symptoms are well controlled with anti-TNF therapy, suggesting that the ocular and articular inflammation develop via differ- ent pathways. The degree to which new-onset uveitis oc- curs in patients receiving anti-TNF therapy has been char- acterized in a retrospective cohort study, with the ma- jority of cases occurring during therapy with etanercept;
of 31 cases of uveitis identified, 19 were in AS, 4 were in psoriatic arthritis, 6 were in rheumatoid arthritis, and 2 were in juvenile idiopathic arthritis. Of the 19 cases asso- ciated with AS, that anti-TNF agent at the time of the first onset of uveitis was etanercept in 12 cases, infliximab in 4 cases, and adalimumab in 3 cases; the pattern of results was similar among 121 cases identified in a systematic lit- erature review [6]. In South Korea, Kim et al. [7]. re-
Sung Jae Choi
336 J Rheum Dis Vol. 22, No. 6, December, 2015
ported case series of 16 new-onset uveitis among 363 AS patients receiving TNF inhibitor therapy. Intriguingly, all 16 patients were receiving etancercept and no new-onset uveitis was reported in infliximab or adalimumab patients.
In a previous issue of this journal, Koo et al. [8] demon- strated the relative incidence rate of uveitis, including the first episode while using TNF inhibitors and concluded there was no difference in the incidence rate of uveitis among the three TNF inhibitors. Eight years of follow up, analysis of survival using the Kaplan-Meier method and Cox proportional hazards model are the strong points of this study. And they found the overall incidence rate of new onset uveitis after TNF-inhibiting therapy was 19 per 1,000 person-years (pys). Among three TNF inhibitors, the new onset uveitis for etanercept was 24/1,000 pys, for adalimumab was 15/1,000 pys, for infliximab was 7/1,000 pys, respectively. There must be a tendency or increased hazard ratio in patient who used etanercept was 1.6 to 3.4 than that of infliximab and adalimumab, however, there was statistically no difference of incidence rate in three TNF inhibitors. Also, the cumulative uveitis-free rate in the three TNF inhibitors showed no difference regardless of whether new onset uveitis or pre-existing uveitis flare.
This study has two shortcomings that should be considered. First, this was a retrospective electronic med- ical record review design in single center. So, relatively small number of patients and loss of follow-up might be influence the incidence rate of uveitis. Also, physician’s preference of selecting TNF inhibitors might be biased to using monoclonal antibody agent to the patients who al- ready have uveitis history, based on previous clinical trial data. Second, causality between specific TNF inhibitor and development of uveitis is not clear. Whether the TNF inhibitor has induced the uveitis or lack of efficacy of the TNF inhibitor couldn’t prevent uveitis flare.
In conclusion, a considerable proportion of the AS pa- tients experienced uveitis flare and approximately half of them developed new onset uveitis even during their treat- ment with TNF inhibitor. Although there was no statisti-
cally different uveitis flare rate among three TNF in- hibitors in this study, it might be helpful for patients de- veloping uveitis during soluble TNF receptor agent to change monoclonal TNF antibody agents. Future direc- tion of uveitis incidence study in TNF users needs to be done in large population based prospective registry data, meta-analysis, and network analysis.
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.
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