Rheumatology Advance Access originally published online on March 17, 2008
Rheumatology 2008 47(5):731-732; doi:10.1093/rheumatology/ken091
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LETTERS TO THE EDITOR |
Do TNF-blockers reduce or induce uveitis?
1Department of Rheumatology and 2Department of Biostatistics, Hospital Universitario La Paz, Madrid, Spain.
Correspondence to: T. Cobo-Ibáñez, Department of Rheumatology, Hospital Universitario La Paz. Po Castellana 261. 28046 Madrid, Spain. E-mail: tcoboiba{at}yahoo.es
SIR, Uveitis is a well-known manifestation of SpAs that may lead to functional impairment. TNF-blockers are effective for treating SpA-related uveitis flares [1], but recent retrospective studies support the possibility of differential TNF-blockers effectiveness, with infliximab or adalimumab showing a higher efficacy than etanercept in the treatment of uveitis [2–4]. In addition, Lim et al. [5] have recently published the finding that etanercept may induce new uveitis flares. During the last 2 years, we have conducted a study with the objective of investigating the impact of TNF-blockers on the appearance of new flares of uveitis in patients with SpAs who exhibit uveitis flares before beginning therapy for the rheumatic disease.
All clinical records of patients with SpAs with a previous acute anterior uveitis who received treatment with TNF-blockers in our department after January 1999 were reviewed. After the study began in October 2005, all data from new uveitis flares in patients with SpAs treated with TNF-blockers were registered prospectively in our database. Flares data were calculated by exposure time and compared both before and after the commencement of therapy by a repeated measurements analysis of variance. The quantitative and qualitative variables were compared between groups with the Mann–Whitney U-test and Fisher's exact test, respectively.
Out of 150 patients with SpAs on TNF-blockers therapy, 19 (12.7%) had uveitis flares prior to starting the treatment. Of these, 11 (58%) were women, 18 (94.7%) had HLA-B27, 10 were on etanercept and nine patients were on infliximab. One patient was switched from etanercept to infliximab because of the recurrence of uveitis and was analysed in both groups.
The types of SpAs were: 15 AS, two undifferentiated SpAs and two PsA. The patterns of uveitis were: 13 recurrent acute unilateral, five recurrent acute bilateral and one chronic bilateral. The mean age at the first flare of uveitis and at the diagnosis of the SpA was 38.15 ± 10.43 and 35.20 ± 11.5 yrs, respectively. The mean age at the onset of TNF-blockers therapy was 48.25 ± 11.1 yrs and the mean duration of the SpA at this time was 13.22 ± 10.18 yrs. The mean duration of the TNF-blockers treatment was 2.98 ± 1.7 yrs. The demographic characteristics of the different groups of treatment were comparable (data not shown).
The number of uveitis flares per patient in the exposure time before starting TNF-blockers was 0.61 ± 0.3 and 0.52 ± 0.4/yr for the infliximab and etanercept groups, respectively. These values changed to 0.05 ± 0.16 and 0.82 ± 0.99, respectively, during the therapy. We have not observed any uveitis flares in our patients treated with adalimumab since this drug was approved for SpAs in our country after starting this study. The incidence of uveitis in the infliximab group was 61.73 cases per 100 patient-years before treatment, and this number decreased to 2.64 after starting the therapy. In the etanercept group, the incidence changed from 34.29 before treatment to 60 cases per 100 patient-years after starting the therapy. This evolution of the uveitis flares was found to be significantly different between both groups (P = 0.041, Fig. 1).
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Only one out of 10 patients developed a new uveitis flare during infliximab treatment. Six of the 10 patients on etanercept had new uveitis flares during the treatment.
Some studies seem to support the possibility of a differential effectiveness of etanercept, adalimumab and infliximab in the treatment of uveitis in favour of both mAbs [2, 6], and other studies suggest a poor effect of etanercept in treating uveitis [7, 8]. In addition, a review of patients with ocular inflammatory disease treated with etanercept found that 17 patients developed uveitis, scleritis and orbital myositis [9]. For this reason, an interesting question is whether etanercept would induce uveitis flares like others drugs such as bisphosphonates. With the intention to clarify this point, clinical trials in patients with AS treated with TNF-blockers or a placebo were reviewed in two articles [1, 10]. These studies showed a higher reduction of uveitis flares in patients treated with infliximab. Etanercept did not increase the number of uveitis cases with respect to placebo groups in the trials, and therefore, appears at least not to increase uveitis. In a recently published registry-based study [5], however, the communication of uveitis cases as an adverse effect associated with etanercept was significantly higher than with infliximab and adalimumab. The odds ratios of 5.375 (P < 0.001) and 8.6 (P < 0.01), respectively, suggest that etanercept can induce uveitis flares. Our findings may support this conclusion; furthermore, our data were collected prospectively, which strengthens our results. Other previous studies that have tried to address these questions either retrieved retrospective data [5, 6, 9] or collected data of AS patients with no specific previous episodes of uveitis [1, 10].
In conclusion, patients exhibiting SpAs show a greater improvement in the frequency of uveitis flares after treatment with infliximab than etanercept. The potential role of etanercept in causing uveitis flares requires further study.
Disclosure statement: The authors have declared no conflicts of interest.
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References |
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