A20: Understanding the Use and Biology of TNF Therapy in JIA-Clinical Outcomes
Authors: Daniel J. Lovell, Anne Johnson, Yuki Kimura, Steven J. Spalding, Paula W. Morris, Beth S. Gottlieb, Karen Onel, Judyann C. Olson, Barbara Edelheit, Michael Shishov, Lawrence Jung, Elaine Cassidy, Sampath Prahalad, Murray H. Passo, Timothy Beukelman, Jay Mehta, Kara M. Schmidt, Dirk Foell, Bin Huang, Edward H. Giannini
Journal: Arthritis & Rheumatology (2014)

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 (c2 6.7, p 0.03). ANA status, MTX use, and type of anti-TNF were not associated with the ability to maintain CID (c2 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+ ((c2 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 ((c2 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.