Tapering Methotrexate Before TNF Inhibitor Reduces Flare Rates for JIA
SAN DIEGO, CA—Flare rates in patients with juvenile idiopathic arthritis (JIA) are high and can be reduced by tapering methotrexate (MTX) first before tumor necrosis factor inhibitors (TNFi), research presented at the 2013 ACR/ARHP Annual Meeting has found.
Combination therapy of TNFi with MTX is a well-established treatment for JIA that has significantly changed disease outcomes. Since the relapse rate in these patients is high, research has focused on determining the ideal timing and method of tapering medications once disease control is reached.
In a retrospective single-center observational cohort study, Caroline Chang, MD, from the Children's Hospital Los Angeles, Los Angeles, CA, and colleagues studied 194 patients with polyarticular JIA (pJIA) seen at the institution's pediatric rheumatology clinic between January 2000 and December 2011.
The majority of participants (n=161; 83%) were female, with 135 (61%) of Hispanic ethnicity and 85 (39%) of non-Hispanic ethnicity. Mean age at disease onset was 9.9 years (1—18). Inactive disease was defined using Wallace criteria, and flare was defined as no longer fulfilling these criteria for more than 1 visit.
Researchers performed a flare-free survival analysis, studying four treatment arms of patients with inactive disease who had used tapered medications: TNFi + MTX, tapered off MTX first (Group 1, n=46), TNFi + MTX, tapered off TNFi first (Group 2, n=20), MTX monotherapy (Group 3, n=38), and TNFi monotherapy (Group 4, n=9). Outcomes were also evaluated based on rheumatoid factor (RF) status.
After a mean of 48 months, 143 of 220 patients (65%) with pJIA achieved inactive disease. Patients who were tapered off TNFi first (Group 2) had a significantly worse outcome, with only 47% remaining flare-free for 12 months following TNFi despite continued MTX therapy compared to 90% of patients who weaned MTX first and continued TNFi (P<0.0005).
After a mean of 11 months (range 0—75) with inactive disease, 28% of pJIA patients were able to discontinue all medications. Compared to the other treatment arms, Group 3 had significantly better flare-free survival compared to Group 1. “Time to flare was independent of time in remission and RF status,” noted Dr. Chang.The authors concluded that weaning TNFi first carries a significantly higher risk of flare than weaning MTX first. “After discontinuation of all medications, pJIA patients on MTX monotherapy had better flare-free survival compared to those on combination therapy, possibly due to inherently milder disease,” the researchers added.