A20: Understanding the Use and Biology of TNF Therapy in JIA-Clinical Outcomes.

BACKGROUND/PURPOSE: Treatment with anti-TNF therapies (anti-TNF) for polyarticular forms (extended oligo, Poly RF +/-) of JIA (PF-JIA) results in >50% demonstrating clinically inactive disease (CID). The aims of this study were to determine the frequency, timing and predictors of flare upon withdrawal of anti-TNF in PF-JIA in CID.

METHODS: In 16 centers 137 children with PF-JIA in CID on anti-TNF were enrolled and followed for ≥14 mos. If CID was maintained for the first 6 study mos, then anti-TNF was stopped. The primary outcome variable was a validated definition of disease flare within 8 months after stopping anti-TNF. Background meds were stable. Blood for S100, DEK, DNA and RNA was drawn for current and future biomarker and genetic studies.

RESULTS: The study population included 18 (13%) extended oligarticular, 17 (12%) RF+ Poly and 102 (74%) RF- Poly JIA patients. At enrollment, age (mean/median/range) was 11.3/11.6/3.4-20.1 yrs; disease duration was 5.0/4.1/0.6-18.6 years; 103 (75%) were females and 64 (47%) were ANA+. Duration of CID at baseline was 1.2/0.5/1 day-12.1 yrs. Anti-TNF was etanercept in 106 (77%), 25 (18%) adalimumab and 6 (5%) infliximab. 40% were on MTX at baseline (mean/median dose 0.4/0.4 mg/kg/week). Other meds: 1 leflunomide, 2 hydroxychloroquine, and 1 prednisolone. 31 (23%) subjects were discontinued from the study in the first 6 mos: 23 (17%) due to loss of CID, 5 (4%) med noncompliance, 2 (1%) moved/LTF, 1 (1%) ILAR subtype changed (oligo to psoriatic). For the extended oligo, Poly RF- and Poly RF+ categories 94%, 82% and 60%, respectively, maintained CID for the first 6 months (c(2) 6.7, p 0.03). ANA status, MTX use, and type of anti-TNF were not associated with the ability to maintain CID (c(2) p values 0.48, 0.14, and 0.75, respectively). 106 (77%) subjects maintained CID for the first 6 months and stopped anti-TNF as per protocol. 67/106 (63%) maintained CID for ≥8 mos off anti-TNF while 39 (37%) flared. Time without flaring after stopping anti-TNF therapy was duration from the month 6 visit to the last study visit (mean/median/range for duration of followup was 249/250/126-322 days). The mean/median/range for time to flare was 108/105/7-271 days. Time to flare (days) for etanercept was 105/105/7-271, adalimumab 119/120/28-238 and infliximab 28/28/28. Flare was seen in 47% (8/17) extended oligo, 37% (30/80) poly RF- and 11% (1/9) poly RF+ ((c(2) p-value 0.19). In those on background MTX, 33% (13/40) flared at a mean of 90 days, while those not on background MTX, 39% (26/66) flared at a mean of 113 days ((c(2) p-value 0.48). Using univariate analysis of variance, only weak correlations of MTX dose, disease duration, and CID duration with flare/no flare were seen (Spearman correlations -0.03, -0.17, -0.19, respectively).

CONCLUSION: In this prospective multicenter study, 77% of the PF-JIA patients were able to maintain CID for the first 6 months on anti-TNF. Discontinuation of anti-TNF in PR-JIA (who have demonstrated on average 1.8 years of CID) resulted in a flare rate of 37% within 8 mos. Clinical parameters had only minimal predictive ability. Ongoing work includes biomarker identification and continued follow-up of the cohort.