With RA in Remission, Tapering of Conventional DMARDs May Lead to Disease Flares for Some Patients

By Reuters Staff

May 05, 2021

NEW YORK (Reuters Health) - In patients with rheumatoid arthritis (RA) in remission taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), cutting the drug dose in half could lead to more disease flares, according to a randomized controlled trial.

Sustained remission is now achievable for RA patients receiving csDMARDs, but how to best manage patients in clinical remission remains unclear.

In the ARCTIC REWIND study, researchers assessed the effect of csDMARD tapering on RA flares, compared with continued stable csDMARD therapy, in patients with RA in remission (c <1.6, with no swollen joints) while on stable csDMARD therapy for at least 12 months with no biologic therapy. The most common csDMARD regimen was methotrexate monotherapy at a mean dose of about 20 mg/week.

The primary analysis population consisted of 77 patients randomly allocated to half-dose csDMARD therapy and 78 who remained on stable-dose csDMARD therapy. In both groups, patients were about 55 years old and about two-thirds were women.

Reducing the dose of csDMARDs by half led to significantly more flares at one year. Flares occurred in 19 patients (25%) in the half-dose csDMARD group versus five (6%) in the stable-dose csDMARD group - a risk difference of 18 percentage points, which failed to meet the prespecified noninferiority margin of 20 percentage points, report Dr. Siri Lillegraven with Diakonhjemmet Hospital, in Oslo, Norway, and colleagues.

"These findings do not support treatment with half-dose therapy," they write in JAMA.

But the authors of a linked editorial say a "closer look may yield a different interpretation."

Dr. Jeffrey Curtis with University of Alabama at Birmingham and colleagues note that three-quarters of patients who went to half-dose therapy remained in remission. And when flares did occur, they were typically mild.

"Most patients had low disease activity, and remission was regained after medication doses were increased," they note.

Among 22 secondary outcomes measured at the end of the 12-month trial, "consisting of a diverse set of RA disease activity measures, musculoskeletal ultrasound, and patient-reported outcomes such as pain, fatigue, and physical function, none showed significant differences between the treatment groups," they add.

Remission rates were high in both groups: 92% in the stable-dose group and 85% in the half-dose group. Although there were few serious side effects, "as expected given the excellent safety profile of these therapies," fewer adverse events occurred in the half-dose group than the stable-dose group (34 patients, 44% vs. 42 patients, 54%).

"Based on results from this trial, attempting dose reduction for patients in remission may be reasonable for some patients," the editorialists say.

"While the ARCTIC REWIND study does not support mandatory reduction in csDMARDs for all patients in remission, it provides some evidence to guide discussions of dose reductions for patients who are have adverse drug effects or who have other reasons to reduce immunomodulatory treatment. The findings suggest that reducing csDMARD dose by half may be successful for some patients, and patients who experience disease flare are likely to quickly recover remission," they conclude.

The study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors have no relevant disclosures.

SOURCE: https://bit.ly/3xJ6tV7 and https://bit.ly/3vELdOv, JAMA, online May 4, 2021.