Patients with rheumatoid arthritis who achieved clinical deep remission were more likely to maintain long-term remission and appeared less vulnerable to relapse during treatment tapering than patients who met less stringent remission criteria, according to findings published in RMD Open.
In a single-center observational cohort study, researchers evaluated 145 patients with rheumatoid arthritis who achieved remission based on the Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP). Patients were required to have at least 5 years of follow-up following remission and at least two DAS28-CRP assessments per year.
Clinical deep remission (CliDR) was defined as no tender or swollen joints on a 28-joint count, along with normal C-reactive protein and erythrocyte sedimentation rate levels. Of the 145 patients, 32 met CliDR criteria and 113 achieved DAS28-CRP remission without meeting CliDR criteria.
At 5 years, 63% of patients in the CliDR group maintained sustained remission compared with 38% of patients in the non-CliDR group. Sustained remission was defined as DAS28-CRP less than 2.6 at every visit for at least 6 consecutive months, without an interim increase of at least 0.6 units or escalation of disease-modifying antirheumatic drug therapy.
The researchers noted that existing remission definitions, including Simplified Disease Activity Index, Clinical Disease Activity Index, and American College of Rheumatology/European Alliance of Associations for Rheumatology Boolean remission criteria, can still permit low levels of residual synovitis. CliDR was designed to reflect complete absence of clinically detectable joint inflammation.
Relapse was defined as a DAS28-CRP increase greater than 0.6 from baseline together with a DAS28-CRP greater than 2.6 at a scheduled follow-up visit. Relapse occurred in 12 of 32 patients in the CliDR group and 70 of 113 patients in the non-CliDR group.
During the 5-year follow-up period, 76 patients underwent treatment tapering. Drug tapering was modeled as a time-dependent covariate because tapering occurred at different points during follow-up.
Among patients without CliDR, tapering was associated with an 8.5-fold higher relapse hazard. The association between tapering and relapse was significantly attenuated among patients who achieved CliDR, with an interaction hazard ratio of 0.26, suggesting the effect of tapering on relapse was substantially lower in the CliDR group.
However, the investigators emphasized that the tapering hazard ratio within the CliDR group was derived indirectly and was not directly tested for statistical significance. In addition, during periods without tapering, relapse hazard did not differ significantly between the CliDR and non-CliDR groups, suggesting the potential benefit of CliDR may be most clinically relevant when treatment reduction is being considered.
The findings suggest that remission depth may provide additional prognostic information beyond DAS28-CRP remission alone, particularly when physicians are evaluating whether medication tapering may be appropriate. However, because the study was observational, the findings cannot establish that achieving CliDR directly reduces relapse risk or proves tapering safety.
The researchers noted several limitations, including the single-center design, modest sample size, and limited statistical power to detect smaller effect sizes. The cohort was also highly selected: approximately 97% of patients were anti-cyclic citrullinated peptide antibody positive, and fewer than 10% received biologic disease-modifying antirheumatic drugs, limiting generalizability to broader rheumatoid arthritis populations and biologic-treated patients.
“Our findings suggest that achieving [clinical deep remission] is associated with significantly higher sustained remission rates in [patients with rheumatoid arthritis],” the researchers wrote.
Disclosures: The researchers reported no competing interests. The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China.
Source: RMD Open