Background/Purpose: Sustained remission is the goal of rheumatoid arthritis (RA) care, and more patients reach and maintain this state on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) after the implementation of treat-to-target strategies. The knowledge about whether csDMARDs can be tapered in RA remission is limited. The primary objective of the study was to assess the effect of tapering of csDMARDs on the risk of flares in RA patients in sustained clinical remission.

Methods: In the non-inferiority ARCTIC REWIND trial, RA patients in clinical remission for at least 12 months on stable csDMARD therapy were randomly assigned to continued stable csDMARD or half dose csDMARD, with visits every four months. Patients had to be in DAS remission at inclusion with no swollen joints (of 44 assessed). 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 2 swollen joints, or both the physician and patient agreed that a clinically significant flare had occurred). The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population using mixed effect logistic regression. Radiographic joint damage at 0 and 12 months was scored by van der Heijde modified Sharp score (progression: ≥1 unit change/year). Clinicaltrials.gov number NCT01881308.

Results: We enrolled 160 patients, 155 received the allocated treatment strategy. Baseline characteristics were overall well balanced in the two arms (Table 1). 61/78 (78.2%) patients in the stable csDMARD arm and 65/78 (84.4%) in the half-dose csDMARD arm were methotrexate monotherapy users. In the primary analysis, 5/78 (6.4%) of patients in the stable csDMARD arm experienced a flare during the 12 months, compared to 19/77 (24.7%) in the half-dose csDMARD arm, giving a risk difference (95% confidence interval [CI]) of 18.3% (7.2% to 29.3%, Figure 1). Non-inferiority could not be claimed as the confidence interval crossed the non-inferiority margin. However, the confidence interval did not include the null, showing superiority of the stable arm over the half-dose arm, with similar results in methotrexate monotherapy users. In the stable arm, 2/5 (40.0%) adjusted DMARD medication following the flares, compared to 18/19 (94.7%) in the half-dose arm. No progression of radiographic joint damage was observed in 79.5% of patients on stable DMARDs and 62.7% in the half-dose arm, difference (95% CI) -17.7% ( -33.0%, -2.3%, Figure 2E). At 12 months, 67 (91.8%) patients in the stable arm and 63 (85.1%) patients in the half-dose arm were in DAS remission (Figure 2), with similar results for other remission definitions. We observed 75 adverse events in the stable arm and 53 in the tapered arm, with serious adverse events in 2 (2.6%) of patients in the stable arm and in 4 (5.1%, including two serious infections) of patients in the tapered arm.

Conclusion: In RA patients in sustained remission on csDMARDs, continued csDMARD therapy with stable doses led to significantly fewer disease activity flares and less frequent radiographic joint damage progression than tapered csDMARD treatment. 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tapering-of-conventional-synthetic-disease-modifying-anti-rheumatic-drugs-in-rheumatoid-arthritis-patients-in-sustained-remission-results-from-a-randomized-controlled-trial/