Longer Inactive JIA Disease Before Stopping MTX Reduces Risk of Flares, Study Finds

Longer Inactive JIA Disease Before Stopping MTX Reduces Risk of Flares, Study Finds

Juvenile idiopathic arthritis (JIA) patients who spend longer periods without disease worsening before discontinuing methotrexate (MTX) treatment have significantly lower flare rates, a German study reports.

In the study, “Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA,” published in the Annals of the Rheumatic Diseases, researchers investigated a group of JIA patients who stopped taking MTX therapy to assess the reasons for discontinuing treatment.

The study included 1,514 JIA patients who started treatment with MTX after a mean disease duration of 2.1 years and were enrolled in the German Biologics in paediatric rheumatology Register (BiKeR) and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation (JuMBO).

Patients were also receiving other treatments to manage symptoms — 85.3% of the JIA patients were on nonsteroidal anti-inflammatory drugs, 18.8% were treated with oral glucocorticoids, and 30.7% with intra-articular glucocorticoids — before the start of the study.

Researchers analyzed the period of time in which patients displayed disease inactivity — that is, with no significant worsening and defined by a Clinical Juvenile Arthritis Disease Activity Score of one or lower — and the frequency of adverse events and disease flares after they discontinued methotraxate.

JIA flares were considered as the re-occurrence of at least moderate disease activity or the restart of treatment with a disease-modifying antirheumatic drug.

Results showed that the majority of the patients, 982 out of 1,514 (64.9%), discontinued MTX after a median treatment duration of 2.3 years.

Stopping the treatment was primarily due to its ineffectiveness (in 36.9% of the cases), which led the physician to discontinue methotrexate or add a biologic therapy, or due to the fact that an inactive disease state was reached (in 32.1% of the cases).

Patients’ or parents’ decision and MTX intolerance were other frequently given reasons for discontinuing treatment.

Among those who stopped taking MTX because they reached inactive disease, 58.2% experienced a flare on follow-up.

Importantly, the likelihood of a flare was dependent on how long patients had been experiencing no disease worsening before MTX discontinuation. The shortest this time was, the more likely they were to experience a flare.

Patients with inactive disease for less than six months before stopping MTX had the highest flare rates (84 of 117, or 71.8%) while those with a disease considered inactive for more than 12 months showed a significantly reduced flare rate (58 of 119, or 48.7%).

The majority of patients with flares (62.5%) required initiation of treatment with disease-modifying antirheumatic drugs, including re-initiation of MTX in 56.6% of the cases, etanercept (Enbrel) in 4.3%, and other therapies in 1.6%.

Researchers also noted that patients with oligoarthritis (a mild form of arthritis affecting two to four joints) had significantly increased flare rates (67%) compared with other JIA types. In addition, methotrexate was initiated later in the disease course for patients with oligoarthritis — 2.7 years vs. 1.8 years for other JIA types.

Concerning safety, MTX intolerance was the most common adverse event reported, including nausea, aversion, and vomiting, affecting 307 patients (20.3%) and comprising a total of 441 occurrences. The second most adverse event reported was infections, accounting for 183 events.

In total, 1,058 adverse events were reported in 540 (35.7%) patients, a small number of them medically serious.

In addition, researchers saw no difference between oral or subcutaneous MTX treatment in terms of adverse event incidence.

The team concluded that “patients who spent at least 12 months in inactive disease before MTX discontinuation had a significantly lower flare rate,” and suggested that “tapering and withdrawing of medication is complex and should be based on the needs of individual patients.”

“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 MTX intolerance under continuing treatment,” researchers concluded.

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