Odds of DMARD-free remission in rheumatoid arthritis may depend on biological DMARD use
Key takeaways:
- In two studies, no patients with rheumatoid arthritis using biological DMARDs ever had sustained DMARD-free remission.
- Sustained DMARD-free remission is more likely among those not requiring biological DMARDs.
Although sustained remission free of disease-modifying antirheumatic drugs “does not seem attainable” for patients with rheumatoid arthritis requiring biological DMARDs, it is possible for those who do not require them, according to data.
The finding calls into question a EULAR recommendation, based on potentially flawed studies, discouraging DMARD cessation due to flare risks, Judith W. Heutz, MD, of the department of rheumatology at Erasmus Medical Center, in the Netherlands, and colleagues wrote in The Lancet Rheumatology.
“[A systematic review] showed that sustained DMARD-free remission can be reached in approximately 20% of patients,” Heutz and colleagues wrote. “However, the 2022 European Alliance of Associations for Rheumatology (EULAR) recommendations discourage complete DMARD cessation in all patients with rheumatoid arthritis due to risk of flares.
“The evidence behind the EULAR recommendation is obtained from studies in subgroups of patients using biological DMARDs or in subgroups of patients positive for anti-citrullinated protein antibodies (ACPA) with high disease activity, however these subgroups only represent part of the total rheumatoid arthritis population,” they added.
Heutz and colleagues hypothesized that, as a group, patients who require biological DMARDs may stand less of a chance of sustaining DMARD-free remission than those who did not require biological DMARDs. To test this, they analyzed prospectively collected data on the treatment of patients with early RA from two sources: the Leiden Early Arthritis Clinic (n = 627; 62% women; mean age, 60 years) and the Rotterdam Early Arthritis Cohort (n = 425; 67% women; mean age, 54 years), a multicenter, stratified, single-blinded trial.
The Leiden Early Arthritis Clinic data included the rates of sustained DMARD-free remission for up to 5 years of follow-up, while the Rotterdam Early Arthritis Cohort had 3 years of follow-up. The researchers used Kaplan-Meier curves to compare DMARD-free remission — defined as no clinical synovitis for at least 1 year after ceasing DMARDs — among patients who did or did not receive biological DMARDs.
In the Leiden Early Arthritis Cohort, no patients who received a biological DMARD had sustained DMARD-free remission, compared with 37% of those who did not use them (HR = 0.02; 95% CI, 0-0.1), according to the researchers.
Similarly, in the Rotterdam Early Arthritis Cohort, none of the patients treated with biological DMARDs demonstrated sustained DMARD-free remission, while 15% of patients not treated with biological DMARDs did achieve sustained remission (HR = 0.03; 95% CI, 0-0.21).
“For a subgroup of patients with early rheumatoid arthritis with more severe disease, characterized by biological DMARD use, reaching sustained DMARD-free remission is unlikely,” Heutz and colleagues wrote. “In contrast, in the larger subpopulation of patients with early rheumatoid arthritis not requiring biological DMARDs, the likelihood of reaching sustained DMARD-free remission is substantially greater, especially when patients are ACPA-negative.
“Therefore, the EULAR recommendations on DMARD cessation might suffer from ascertainment bias, since only part of the rheumatoid arthritis population was represented in the studies used to guide these recommendations,” they added. “Future guidelines about DMARD cessation might therefore be amended.”
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