Norway: Advancements in Rheumatoid Arthritis Therapy

According to a research letter published in JAMA, due to advancements in rheumatoid arthritis (RA) therapy, patients can achieve sustained remission.

It is already known that Conventional DMARDs are the main therapeutics for RA majorly needed by patients. These have side effects, so there needs to be more data on whether tapering the dosage or stopping them can achieve remission.

In this research letter, the author mentioned, "The recommended treatment suggests tapering of dosage of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in RA patients. Though tapering may cause more flares to appear compared to full dose therapy, tapering can be successful in some patients."

Lillegraven and colleagues conceived a two-phase trial called ARCTIC REWIND conducted in 10 Norwegian hospitals. The results of the first phase (2021) answered that reducing the dose is unsafe, with 12-month flare rates of 25% in the half-dose group compared to 6% in the full-dose group. The difference exceeded the margin of non-inferiority.

Considering the second phase, it took patients in phase one's half-dose arm who did not flare and re-randomized them to either stick with the half-dose or stop DMARDs entirely.

American College of Rheumatology/European Alliance of Associations for Rheumatology criteria defined remission with no swollen joints out of 44 assessed. In contrast, flares were described as 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.

Study Results

• Within 12 months, 10 of 26 patients assigned to DMARD discontinuation had disease flare compared with five of 30 who remained on half-dose therapy, with a risk difference of 21.5 percentage points.
• Eight of the ten patients who flared after discontinuing returned to remission quickly after full-dose DMARDs were started again, as did two of three in the continuing half-dose arm.

The researchers have addressed the importance of structured follow-up of DMARD treatment-free patients because if a flare occurs, then restarting drugs to restore remission will be effective.

We reported more frequently appearing flare when tapering csDMARDs vs full-dose therapy, but tapering could be successful in some patients, they said.

They also mentioned uncertainty on whether the discontinuation of csDMARDs is realistic and sustainable.

The study's main limitations were the small sample size and lack of blinding in treatment assignment.

Further Reading

Lillegraven S, Paulshus Sundlisæter N, Aga A, et al. Discontinuation of Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis and Excellent Disease Control. JAMA. 2023;329(12):1024–1026. doi:10.1001/jama.2023.0492