Do tumor necrosis factor inhibitors cause uveitis? A registry‐based study

Abstract

Objective. Population-based studies of patients with ankylosing spondylitis indicate that tumor necrosis factor (TNF) inhibitors prevent uveitis. Paradoxically, anecdotal reports implicate etanercept as a cause of uveitis. Therefore, using the information from 2 drug events databases, the purpose of this study was to assess reported cases of uveitis associated with the use of TNF inhibitors.Methods. Uveitis cases occurring in the US associated with etanercept, infliximab, or adalimumab therapy that were reported to 2 spontaneous reporting databases prior to January 1, 2006 were reviewed.Results. Overall, there were 43 cases of uveitis associated with etanercept, 14 associated with infliximab, and 2 associated with adalimumab. After normalizing for the estimated number of patients treated with each medication, etanercept was associated with a greater number of uveitis cases than infliximab (P < 0.001) and adalimumab (P < 0.01), while no such association was found between adalimumab and infliximab (P > 0.5). Using a priori criteria to avoid including patients whose underlying disease was associated with uveitis, 20 cases associated with etanercept, 4 cases associated with infliximab, and 2 cases associated with adalimumab were identified. A repeat analysis again revealed a greater number of uveitis cases associated with etanercept (P < 0.001 versus infliximab).Conclusion. Etanercept therapy is associated with a significantly greater number of reported uveitis cases in comparison with infliximab and adalimumab in 2 medication side effect registries. These results are consistent with previous studies and suggest that this relationship is drug specific and not related to TNF inhibitors as a whole. However, our findings do not support the use of infliximab over etanercept; rather, if a patient develops uveitis during etanercept therapy, then a change to infliximab may be warranted.

Juvenile idiopathic arthritis-associated uveitis

“…Several studies have reported flares or new-onset uveitis while on etanercept [65][66][67]. Evidence from national registries suggests that etanercept is associated with a greater number of uveitis cases than adalimumab or infliximab [68]. However, no definite causative effect of etanercept can be proved from these retrospective observational studies and the prescribing pattern of the different anti-TNFs may be a confounding factor [69].…”

Sarcoid-related Uveitis Occurring During Adalimumab Therapy

“…5 Lim et al have recently relied on a database of 2 drug events to assess reported cases of uveitis associated with the use of anti-TNFα. 5 They found that etanercept was associated with a significantly greater number of uveitis in comparison with infliximab and adalimumab.…”

New Treatment Alternatives in the Management of Non-İnfectious İntraocular İnflammations: Biologic Agents

“…[17][18][19] Bu konuda yap›lan çal›flmalarda üveit harici çeflitli endikasyonlar nedeniyle etanersept kullanan hastalarda üveit s›kl›¤› artarken, infliksimab veya adalimumab kullan›lan gözlerde üveit s›kl›¤›n›n azald›¤› bildirilmifltir. [20][21] RA, psoriasis gibi pek çok hastal›kta etanersept ve infiliksimab benzer etkinlik gösterse de üveitte ve Crohn hastal›¤›nda etanersept flu an için tercih edilmemektedir. Genel kan› etanerseptinin Crohn hastal›¤›, Wegener granulomatozu ve sarkoidoz gibi granulamatöz hastal›k-larda baflar›s›z oldu¤u fleklindedir.…”

“…Çünkü di¤er iki ajan›n bu sitokin üzerine bir etkisi bulunmamaktad›r. 20 Bu konudaki di¤er bir teori de, çözünebilir bir reseptör olan etanerseptin, göz için-de ba¤land›¤› TNF-α'n›n yar› ömrünü uzatarak üveit potansiyelini artt›rm›fl olabilece¤idir. 20 Bu etkinlik farkl›l›¤› ile ilgili ileri sürülen bir di¤er teori ise, etanerseptin Thücrelerinin sitokinlere olan yan›t›n› artt›r›rken, infliksimab›n azaltt›¤› fleklindedir.…”

“…20 Bu konudaki di¤er bir teori de, çözünebilir bir reseptör olan etanerseptin, göz için-de ba¤land›¤› TNF-α'n›n yar› ömrünü uzatarak üveit potansiyelini artt›rm›fl olabilece¤idir. 20 Bu etkinlik farkl›l›¤› ile ilgili ileri sürülen bir di¤er teori ise, etanerseptin Thücrelerinin sitokinlere olan yan›t›n› artt›r›rken, infliksimab›n azaltt›¤› fleklindedir. 22 Bu ilac›n flu an için üveit tedavisinde yeri olmamakla birlikte, ilac›n mutlak kontraendikasyonlar›; hamilelik ve emzirme, aktif enfeksiyon (tuberküloz ve kronik aktif hepatit B dahil), konjestif kalp yetmezli¤i (Grade III, IV) iken, relatif kontraendikasyonlar›; HIV veya AIDS varl›¤›, Hepatit C, konjestif kalp yetmezli¤i (Grade I veya II), demyelinizan hastal›klar, maligniteler ve lenfoproliferatif hastal›klar ve canl› afl›lar olarak bildirilmifltir.…”