Uveitis Reactivation in Children Treated With Tumor Necrosis Factor Alpha Inhibitors

Abstract

PURPOSE To evaluate reactivation of pediatric uveitis during/following treatment with TNF-alpha inhibition (anti-TNFα). DESIGN Retrospective cohort study. METHODS We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed. RESULTS Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be “at risk” of the primary (19 for the secondary) outcome. 60% were female, ~half had Juvenile Idiopathic Arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9-87.7%]), than before (21.6% [95% CI: 10.8-40.2%]), anti-TNFα discontinuation. Amongst those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs. infliximab (Hazard Ratio [HR] 13.4, p=0.01, 95% CI: 2.2-82.5) and those with older age at uveitis-onset (HR 1.3, p=0.09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years. CONCLUSIONS Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at one year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression, for more than 1.5 years decreases the reactivation risk.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

“…The Voting Panel recommends that children with controlled CAU on stable medication should be monitored at 3‐month intervals, and those tapering or discontinuing therapy should be monitored at intervals shorter than 3 months, either within 1 month after each change in topical glucocorticoids, and within 2 months of a change in systemic therapy (Figure B). Although the quality of evidence was very low, the recommendations for monitoring were strong due to the potential for harmful consequences of irregular or infrequent monitoring of children with CAU, which could lead to substantial loss of vision and ocular complications from undetected exacerbation of inflammation . Patients were generally concerned about the consequences of infrequent monitoring and agreed that there was little disadvantage to having frequent ophthalmic examinations.…”

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

“…Although the quality of evidence was very Table 1). | 711 low, the recommendations for monitoring were strong due to the potential for harmful consequences of irregular or infrequent monitoring of children with CAU, which could lead to substantial loss of vision and ocular complications from undetected exacerbation of inflammation (20,25). No recommendations were made for patients with uncontrolled chronic anterior uveitis.…”

“…JIA = juvenile idiopathic arthritis; RF = rheumatoid factor; ANA = antinuclear antibody. | 711 low, the recommendations for monitoring were strong due to the potential for harmful consequences of irregular or infrequent monitoring of children with CAU, which could lead to substantial loss of vision and ocular complications from undetected exacerbation of inflammation (20,25). Patients were generally concerned about the consequences of infrequent monitoring and agreed that there was little disadvantage to having frequent ophthalmic examinations.…”

“…There is very low quality of evidence for timing of tapering of topical glucocorticoids and systemic therapy (25,49,50). Some ophthalmologists feel that in selected cases, it is not possible to discontinue topical glucocorticoids altogether, despite attempts to do so, and the patients may continue to receive 1-2 drops/day for extended periods of time.…”

Juvenile idiopathic arthritis-associated uveitis

“…The duration of maintenance therapy on biologic agents is not certain although consensus recommendations suggest continuing treatment for 24 months of inactive disease [39]. One retrospective cohort study (n = 50, 44 % with JIA) has reported on uveitis reactivation after stopping infliximab (n = 45) or adalimumab (n = 5) [64]. Of 19 patients who achieved remission and were subsequently withdrawn from anti-TNFs, 63.8 % had reactivation within 12 months and there did not appear to be an association with duration of medication-induced remission.…”