Sustained DMARD-free remission in subgroups of patients with rheumatoid arthritis: an analysis of two prospective cohorts with early arthritis.

Background: About 20% of patients with rheumatoid arthritis on disease-modifying antirheumatic drugs (DMARDs) can reach sustained DMARD-free remission. Nonetheless, the 2022 EULAR recommendations discourage complete cessation of DMARDs due to flare risk. The evidence behind this recommendation is obtained from trial populations using biological DMARDs, representing only a subgroup of the total population of patients with rheumatoid arthritis. We hypothesised that patients requiring biological DMARDs represent a subgroup that is less capable of reaching sustained DMARD-free remission compared with patients not requiring a biological DMARD.

Methods: In this study we used data from two prospectively followed up populations of patients with early rheumatoid arthritis, the Leiden Early Arthritis Clinic (EAC) and the treatment in the Rotterdam Early Arthritis Cohort (tREACH), a treat-to-target steered trial in which biological DMARDs were started when patients had inadequate response to triple DMARD-therapy (methotrexate, sulfasalazine, and hydroxychloroquine). Patient partners were involved in the design of both the EAC and tREACH. The primary outcome was sustained DMARD-free remission, which was defined as absence of clinical synovitis after discontinuation of DMARDs for at least 1 year. Patients who did or did not receive biological DMARDs in 5 years (EAC) or 3 years (tREACH) were compared using Kaplan-Meier curves.

Findings: 627 patients from the EAC were included, of whom 391 (62%) were female and 236 (38%) were male. The mean age was 60 years (SD 14) and 502 (95%) of 529 patients were White. 89 (14%) of 627 patients had ever used a biological DMARD and 538 (86%) had never used a biological DMARD. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 37% of the patients who never used a biological DMARD reached sustained DMARD-free remission at 5 years (hazard ratio [HR] 0·02, 95% CI 0·00-0·10; p<0·0001). From the tREACH population, 425 patients were included in the study. 286 (67%) patients were female, 139 (33%) were male, and the mean age was 54 years (SD 14); ethnicity data not recorded. 154 (36%) of 425 patients had ever used a biological DMARD and 271 (64%) had never used a biological DMARD during follow-up. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 15% of patients who never used a biological DMARD reached sustained DMARD-free remission at 3 years (HR 0·03, 95% CI 0·00-0·21; p<0·0001).

Interpretation: For the subgroup of patients with rheumatoid arthritis who require biological DMARDs, sustained DMARD-free remission does not seem attainable. In contrast, in patients with rheumatoid arthritis who do not require biological DMARDs, DMARD-free remission is attainable. These data suggest that the current EULAR recommendation to not stop DMARD use might suffer from ascertainment bias. Future recommendations about DMARD cessation should be amended.

Funding: The Dutch Arthritis Foundation and the European Research Council.