Individual therapeutic DAS28-dcrit responses differentiate between effectiveness of rheumatoid arthritis therapies and reflect patient-reported outcomes: retrospective analysis of DAS28 responses in comparative tocilizumab studies

Abstract

Assessment of individual therapeutic responses provides valuable information concerning treatment benefits in individual patients. We evaluated individual therapeutic responses as determined by the Disease Activity Score-28 joints critical difference for improvement (DAS28-d crit ) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-d crit value [DAS28 decrease (improvement) ≥ 1.8] was retrospectively applied to data from two studies of tocilizumab in RA, the 52-week ACT-iON observational study and the 24-week ADACTA randomized study. Data were compared within (not between) studies. DAS28 was calculated with erythrocyte sedimentation rate as the inflammatory marker. Stability of DAS28-d crit responses and European League Against Rheumatism (EULAR) good responses was determined by evaluating repeated responses at subsequent timepoints. A logistic regression model was used to calculate p values for differences in response rates between active agents. Patient-reported outcomes (PROs; pain, global health, function, and fatigue) in DAS28-d crit responder versus non-responder groups were compared with an ANCOVA model. DAS28-d crit individual response rates were 78.2% in tocilizumab-treated patients and 58.2% in anti-TNF-treated patients at week 52 in the ACT-ion study (p = 0.0001) and 90.1% versus 59.1% at week 24 in the ADACTA study (p < 0.0001). DAS28-d crit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-d crit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-d crit response criterion provides robust assessments of individual responses to RA therapy and may be useful for discriminating between active agents in clinical studies and guiding treat-to-target decisions in daily practice.

Sustained effectiveness and safety of subcutaneous tocilizumab over two years in the ARATA observational study

“…Assessments of individual therapeutic responses found that 64% of patients had a DAS28-d crit response, defined as a DAS28-ESR reduction of ≥1.8 from baseline, at week 104. DAS28-dcrit responses were sustained for a median of slightly less than 1 year, consistent with other reports documenting the stability of DAS28-d crit responses (16,26). Time-to-event and Kaplan-Meier analyses did not identify any significant associations between baseline characteristics and DAS28-d crit responses.…”