Background A number of studies have shown that reduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) is possible for rheumatoid arthritis (RA) patients in whom bDMARD treatment has induced clinical remission or low disease activity. However, there have been few studies which have evaluated the background characteristics of patients who have difficulty in reducing bDMARDs despite being in clinical remission or having low disease activity.
Objectives To clarify the characteristics of RA patients who have difficulty with bDMARD reduction despite maintaining clinical remission in the rT-4 study.
Methods This study is a post-hoc analysis of the rT-4 study. Briefly introducing the rT-4 study: 209 RA patients demonstrating both SDAI remission and MMP-3 normalization using bDMARDs for ≥3months were randomly allocated to one of four strategy groups: Standard care (SC group; n=50); SDAI-driven therapy (n=53); MMP-3-driven therapy (n=55); or both SDAI and MMP-3-driven therapy group (Twin; T group; n=51). Dose reduction methodology (every 3 months): ettanercept (ETN) - period between injections increased by one week; tocilizumab (TCZ) - dose reduced by 80mg or period between injections increased by one week; up to a minimum dose of: ETN - 25 mg every 5 weeks; TCZ - 80 mg every 5 weeks or 162 mg every 5 weeks. The dose was reverted to the previous level in the event that the target scores were exceeded, and the lower dose was eventually reattempted after the target was re-achieved. The primary outcome was the difference in the proportion of patients who maintained remission at 12 months among the four groups, compared against a non-inferiority margin of 10%. The results of the rT-4 study revealed that a twin target strategy can achieve effects non-inferior to standard care with regard to maintaining clinical remission.
Specifically, subgroup analysis was carried out between the T and SC groups of the rT-4 study. A factor was defined as significant when the difference in the proportion of patients who maintained remission at 12 months in the two groups across subgroups, exceeded 10%.
Results The requisite margin was recognized only for rheumatoid factor (RF) negativity (35.2%; 95% CIs of 14.4 to 65.0). Others factor were not identified.
Disease activity is likely to be affected by even a small dose reduction of bDMRADS in RA patients who are RF negative, regardless of the presence or absence of anti-citrulline antibody, and it can probably be explained as a nocebo effect. Nocebo effects occur in studies which investigate the effectiveness of drug reduction, and we believe that the nocebo effect is prone to happen in RF-negative patients.
Conclusions The twin target strategy can be used to reduce the dose of bDMARDs for RA patients while maintaining the effectiveness of said bDMARDs, with the exception of RF negative patients.
Disclosure of Interest None declared