Conventional Therapy Bests Tapered Therapy in Rheumatoid Arthritis

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Rheumatoid arthritis patients in sustained remission and receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and who continued therapy with stable doses, had fewer flares and less frequent radiographic joint damage progression than those who received tapered csDMARD treatment, according to a study presented at annual meeting of the American College of Rheumatology in Atlanta on November 12.

More patients with rheumatoid arthritis reach and maintain sustained remission on csDMARDs after the implementation of treat-to-target strategies. However, the knowledge about whether csDMARDs can be tapered in rheumatoid arthritis remission is limited.

The primary objective of the ARCTIC REWIND trial was to assess the effect of tapering of csDMARDs on the risk of flares in rheumatoid arthritis patients in sustained clinical remission.

In the trial, 155 rheumatoid arthritis patients (mean age 55 years) in clinical remission, as measured by the Disease Activity Score (DAS) for 44 joint counts, for at least 12 months on stable csDMARD therapy were randomly assigned to continued stable csDMARD (n=78, 64 percent female, 78.2 percent methotrexate monotherapy users) or half dose csDMARD (n=77, 69 percent female, 84.4 percent methotrexate monotherapy users), with visits every four months. The primary endpoint was the proportion of patients with a disease flare during the 12-month study period (a combination of DAS > 1.6, a change in DAS > 0.6 and at least two swollen joints, or both the physician and patient agreed that a clinically significant flare had occurred). Radiographic joint damage at baseline and 12 months was scored by van der Heijde modified Sharp score (progression: ≥1 unit change/year).

In an interview with Rheumatology Network, Siri Lillegraven, M.D., M.P.H, Ph.D., of Diakonhjemmet Hospital in Oslo, Norway, said “the study aimed to include patients in deep remission, who had been in remission for at least a year. The study was designed as a non-inferiority study, based on the hypothesis that csDMARDs could be tapered in such a patient cohort. We were thus somewhat surprised by the clear difference in flare rates and by the difference in radiographic progression that was observed.”

In the primary analysis, 6.4 percent of patients in the stable csDMARD group experienced a flare during the 12 months, compared to 24.7 percent in the half-dose csDMARD group, giving a risk difference (95% confidence interval [CI]) of 18.3 percent (7.2 percent to 29.3 percent). Non-inferiority, with a margin of 20 percent, could not be claimed.

In the stable group, 40 percent adjusted DMARD medication following the flares, compared to 94.7 percent in the half-dose group. No progression of radiographic joint damage was observed in 79.5 percent of patients on stable DMARDs and 62.7 percent in the half-dose group, difference (95% CI) -17.7 percent (-33 percent, -2.3 percent). At 12 months, 91.8 percent of patients in the stable arm and 85.1 percent of patients in the half-dose arm were in DAS remission, with similar results for other remission definitions.

A total of 75 and 53 adverse events occurred in the stable and tapered groups, respectively, with serious adverse events in 2.6 percent of patients in the stable group and in 5.1 percent, including two serious infections, of patients in the tapered group.

“The results support that if a patient reaches sustained remission in RA on csDMARDs, flares are very rare if stable DMARD dose is continued, and that stable csDMARD therapy should be the preferred choice for these patients.

“We find it interesting that very few disease activity flares occurred if patients in sustained remission received stable treatment, illustrating that the RA disease course can have a favorable outcome, even with the cheapest and globally most available DMARDs,” Dr.  Lillegraven said.

REFERENCE

“LO8 - Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial.” Siri Lillegraven, M.D., M.P.H, Ph.D., 9 a.m., Tuesday, Nov. 12. 2019 ACR/ARP Annual Meeting, Atlanta