RA patients in remission benefit from continued therapy with conventional DMARDs

The ARCTIC REWIND trial showed that tapering methotrexate in rheumatoid arthritis (RA) patients in sustained remission leads to significantly more flares than continuing methotrexate treatment [1].

In the current EULAR guidelines, tapering of a biologic or small molecule is recommended in patients with RA in sustained remission while retaining the conventional (cs) disease-modifying antirheumatic drugs (DMARDs), usually methotrexate [2]. However, the knowledge about whether csDMARDs can be tapered in RA remission is limited. The primary objective of the non-inferiority ARCTIC REWIND trial was to assess the effect of tapering of csDMARDs on the risk of flares in RA patients in sustained clinical remission.

A total of 160 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 4 months. All patients were in Disease Activity Score (DAS) remission with no swollen joints (of 44 joints 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 when both the physician and patient agreed that a clinically significant flare had occurred). Radiographic joint damage at 0 and 12 months was scored by van der Heijde modified Sharp score (progression: ≥1 unit change/year).

In the stable csDMARD arm, 6.4% of patients experienced a flare, compared with 24.7% in the half-dose arm. Superiority of the stable csDMARD therapy was also noticed in the methotrexate monotherapy users (78.2% of patients in the stable csDMARD arm and 84.4% in the half-dose csDMARD arm). In addition, the continued therapy with the full csDMARD dose showed advantages with regard to progression of radiographic joint damage: 79.5% of patients on stable dose showed no progression compared with 62.7% in the half-dose arm. After 1 year, 91.8% of patients in the stable arm and 85.1% in the half-dose arm were in DAS remission. Tolerability was comparable in 2 arms. The authors concluded that RA patients in remission benefit from a stable dose with csDMARDs, since it leads to significantly fewer disease activity flares and less frequent radiographic joint damage progression than tapered csDMARD treatment.

The results of ARCTIC REWIND are in line with the recently published TARA study where tapering a TNF inhibitor in RA patients in remission resulted in similar flare rates compared with tapering methotrexate. Thus, these authors also concluded that it is more sensible to taper the TNF inhibitor first due to possible cost reductions and fewer long-term side effects [3]. Therefore, the suggestion to taper biologics and small molecules in the 2016 guidelines of the ACR will get a level A recommendation in the updated guidelines.

1. Lillegraven S, et al. Abstract L08. ACR 2019, 9-13 November, Atlanta (GA/USA).
2. Smolen JS, et al. Ann Rheum Dis 2017;76:960-77.
3. van Mulligen E, et al. Ann Rheum Dis 2019:78:764-53

 



Posted on 4 February 202028 March 2024