RA in Remission? Stopping DMARDs May Be OK

Most rheumatoid arthritis (RA) patients who maintained remission with half-doses of conventional disease-modifying anti-rheumatic drug (DMARD) therapy and then proceeded to full stoppage stayed flare-free for 1 year, results from a small randomized trial indicated.

Ten of 26 patients assigned to DMARD discontinuation experienced a disease flare within 12 months, compared with five of 30 who remained on half-dose therapy (risk difference 21.5 percentage points, 95% CI -3.4 to 49.7), reported Siri Lillegraven, MD, MPH, PhD, of Diakonhjemmet Hospital in Oslo, Norway, and colleagues in a JAMA research letter.

But eight of the 10 who flared after discontinuing quickly returned to remission after full-dose DMARDs were started again, as did two of three in the continuing half-dose arm.

"The data suggest that [conventional synthetic] DMARD withdrawal might be viable in some patients," Lillegraven and colleagues wrote. Moreover, "structured follow-up of DMARD treatment-free patients is advisable," they added, because restarting the drugs was very effective at restoring remission when flares did occur.

"The results provide a basis for shared decision-making in treatment of patients with RA achieving remission," the group concluded.

Conventional DMARDs remain the backbone of therapy for RA and are the only treatment some patients ever need. Since these agents do come with adverse effects, the question of reducing or even stopping them for those achieving remission has naturally arisen.

To answer it, Lillegraven and colleagues conceived a two-phase trial called ARCTIC REWIND. Conducted in 10 Norwegian hospitals, the first part randomized RA patients in remission to stay on their full-dose DMARD regimen or have it cut by half. Results were published in 2021 with a clear answer: the dose reduction was not safe, with 12-month flare rates of 25% in the half-dose group versus 6% in the full-dose group, with the difference exceeding the prespecified margin for noninferiority.

The second phase is what Lillegraven and colleagues are now reporting. It took patients in phase one's half-dose arm who did not flare (n=56) and re-randomized them to either stick with the half-dose or stop DMARDs entirely.

For both halves of ARCTIC REWIND, remission was defined according to standard American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, with no swollen joints out of 44 assessed. Flares were defined as development of all of the following: two or more swollen joints, a change in 44-joint Disease Activity Score (DAS) of 0.6 points, and a total DAS score above 1.6. Patients were seen in clinic every 4 months and more frequently if disease worsening was suspected.

Although some 40% of patients in the discontinuation arm had flares, these didn't lead to permanent problems in most cases. "Radiographic joint damage progression was absent in 84.0% of patients who discontinued therapy and 69.0% of those who continued half-dose therapy," the researchers reported.

No differences in adverse event rates were seen between arms, the group added.

Limitations included the small numbers of patients and lack of blinding in treatment assignments (i.e., no placebo control in the discontinuation group).

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