The Risk of Uveitis in Patients With JIA Receiving Etanercept

The Challenges of Analysing Real-World Data

Rebecca Davies; Diederik De Cock; Lianne Kearsley-Fleet; Taunton Southwood; Eileen Baildam; Michael W. Beresford; Helen E. Foster; Wendy Thomson; Athimalaipet V. Ramanan; Kimme L. Hyrich


Rheumatology. 2020;59(6):1391-1397. 

In This Article


A total of 2698 patients with non-systemic JIA were recruited at point of starting one of the study drugs (1038 MTX, 540 adalimumab/infliximab, 1120 etanercept). Of these, 95 (9%), 236 (44%) and 73 (7%), respectively, had a history of uveitis at registration and were excluded from further analysis, resulting in a total of 2294 patients in the analysis; 943 MTX, 1047 etanercept and 304 adalimumab/infliximab. Patients in the final adalimumab/infliximab cohort consisted of 243 (80%) starting adalimumab and 61 (20%) starting infliximab. Baseline characteristics are presented in Table 1. The cohorts were relatively similar with respect to age and gender, but patients starting MTX were slightly younger and had much shorter disease duration compared with those starting biologics (median 2 years for both etanercept and adalimumab/infliximab vs 0 years for MTX). Patients starting MTX were more likely to have persistent oligoarthritis and patients starting adalimumab or infliximab were more likely to have enthesitis-related arthritis.

Risk of New Onset Uveitis

There were 44 new diagnoses of uveitis over a total of 5456 person-years of follow-up: 27 in patients on MTX, 16 in patients on etanercept (etanercept-combination = 11, etanercept-monotherapy = 5) and 1 in a patient on adalimumab (Table 2). The majority of cases were unilateral at diagnosis with most children being diagnosed with anterior uveitis. There were no cases of panuveitis reported within this study. Cases were seen most frequently in those patients with oligoarticular or RF-negative polyarthritis (Table 3). Crude incidence rates, presented per 100 person-years, were 1.6 (95% CI 1.0, 2.3) in patients taking MTX, 0.6 (95% CI 0.3, 0.9) in those receiving etanercept and 0.1 (95% CI 0, 0.4) in patients receiving adalimumab or infliximab. The incidence rate was higher in patients in the etanercept-combination when compared with etanercept-monotherapy cohort.

The mean age at uveitis diagnosis was 7 years in the etanercept cohort vs 4 years in the MTX cohort, with time from JIA diagnosis to uveitis onset 4 and 2 years, respectively. The adalimumab patient was over 15 years of age at the time of uveitis diagnosis and this occurred 2 years post-JIA diagnosis. Unadjusted HR showed a reduced risk of uveitis in all etanercept cohorts and the adalimumab/infliximab cohort when compared with patients on MTX; however, after adjusting for propensity deciles, there was no significant difference in the risk of uveitis between patients receiving etanercept or MTX [HR 0.5 (95% CI 0.2, 1.1)]. Although the rates were higher in patients receiving etanercept in combination with MTX compared with those receiving it as monotherapy, this did not reach statistical significance [HR 2.6 (95% CI 0.8, 8.8)].

Similar results were found in sensitivity analysis limited to children with a JIA diagnosis before the 12th birthday and in an analysis censored at the child's 12th birthday (Table 2).

Risk Factors in the Development of Newly Diagnosed Uveitis

A univariable analysis of risk factors in the development of new uveitis (Table 4) found a significant association between development of uveitis and younger age at baseline, shorter disease duration, being of non-white ethnicity and having oligoarticular disease (compared with other ILAR categories excluding RF-negative polyarthritis). Gender, disease severity and functional disability were not found to be significantly associated with development of uveitis in this cohort.