Duration of Inactive Disease Linked to Flare Risk in JIA After Methotrexate Withdrawal

Withdrawal of medication in juvenile idiopathic arthritis prior to 12 months in clinical inactive disease may increase risk of disease flare.

Patients with juvenile idiopathic arthritis (JIA) being treated with methotrexate experienced fewer flares when the disease was inactive for greater than 12 months, according to a recent study published in the Annals of the Rheumatic Diseases.

The prospective study examined methotrexate treatment in patients with JIA (N=1514). Of the 1514 participants, 982 discontinued treatment, most commonly because of ineffectiveness (36.9%) and inability to achieve clinically inactive disease (32.1%). Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, and a flare was defined as reoccurrence of disease activity or restarting treatment. A total of 184 patients experienced a disease flare on follow-up.

A significant correlation was found between length of time the disease was inactive and not experiencing a flare after methotrexate discontinuation (hazard ratio [HR] 0.95; 95% CI, 0.93-0.97; P <00001). Patients with inactive disease for greater than 12 months before treatment discontinuation were less likely to experience methotrexate withdrawal-induced flares (HR 0.50; 95% CI, 0.34-0.74; P =.001).

The most frequently reported adverse event was intolerance of methotrexate, including nausea, vomiting, and aversion.

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The study investigators wrote, “A flare was less common in patients who spent at least 12 months in [clinically inactive disease] before [methotrexate] discontinuation.” They also noted, “Withdrawing treatment in JIA is complex, and currently no guidelines or consented recommendations have been published. The clinician must balance the high risk for disease flares that may prevent the clinician from withdrawing treatment against the risk for [adverse events] and [methotrexate] intolerance under continuing treatment.”


Klotsche J, Minden K, Niewerth M, Horneff G. Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA [published February 16, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211968