Article Text
PDF
Abstract
Background While there have been previous studies into reduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients in clinical remission or with low disease activity, there have been no strategy studies which demonstrated non-inferiority to standard care with regard to maintaining clinical remission while reducing bDMARDs.
Objectives To evaluate whether a therapy strategy using reduced doses of bDMARDs [bDMARDs: etanercept (ETN); tocilizumab (TCZ); abatacept (ABT)] achieving both a simplified disease activity index (SDAI) score of less than 3.3 and normalization of matrix metalloproteinase (MMP) 3 levels is non-inferior in maintaining disease control in patients with RA compared with standard care (rT-4 study).
Methods 223 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=56); SDAI-driven therapy (S group; n=54); MMP-3-driven therapy (M group; n=57); or both SDAI and MMP-3-driven therapy group (Twin; T group; n=56). Method of dose reduction (every 3 months): ETN - period between injections increased by one week; TCZ - dose reduced by 80mg or period between injections increased by one week; ABT - dose reduction by 250 mg 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; ABT - 250 mg every 5 weeks or 125 mg every 5 weeks. The dose was reversed 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%. Secondary outcomes included functional and radiographic progression.
Results Patient characteristic demographics are summarized in Table 1. One hundred ninety-three patients completed the observation period of 12 months and three patients dropped out. Consequently, one hundred ninety-six patients were analyzed (non responder imputation). There was no difference for the rate of reduction dose of bDMARDs at 12 months in S group, M group, and T group: 37.8, 42.3 and 42.9%, respectively (p=0.4176). The M and T groups were non-inferior to the SC group (proportion of patients who maintained remission during the 12 months: 32.7% and 40.0% v 38.2%; a variation of -1.8% and 5.5%, respectively; with 95% CIs of 3.8% to 5.3% and -1.9% to 5.3%, respectively). At month 12, functional status and radiographic progression did not differ between the SC and T groups.
Conclusions Results of the rT-4 study reveal that a twin target strategy can achieve effects non-inferior to standard care with regard to maintaining clinical remission.
Disclosure of Interest None declared