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.

Koehm M; McIntosh MJ; Hofmann MW; Abraham V; Gabay C; Choy EH; Kavanaugh A; Burkhardt H; Behrens F

doi:10.1007/s00296-020-04514-7

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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.

Koehm M Rheumatology and Fraunhofer IME, Branch for Translational Medicine and Pharmacology (TMP), Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany. Michaela.Koehm@ime.fraunhofer.de.
McIntosh MJ Genentech, South San Francisco, CA, USA.
Hofmann MW Chugai Pharma Europe Ltd., Frankfurt am Main, Germany.
Abraham V Genentech, South San Francisco, CA, USA.
Gabay C Geneva University Hospital, Geneva, Switzerland.
Choy EH Section of Rheumatology, CREATE Centre, Cardiff University School of Medicine, Cardiff, UK.
Kavanaugh A University of California, San Diego, San Diego, CA, USA.
Burkhardt H Rheumatology and Fraunhofer IME, Branch for Translational Medicine and Pharmacology (TMP), Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
Behrens F Rheumatology and Fraunhofer IME, Branch for Translational Medicine and Pharmacology (TMP), Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.

2020-02-11

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Rheumatology international. - 2020

English 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-dcrit) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-dcrit 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-dcrit 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-dcrit responder versus non-responder groups were compared with an ANCOVA model. DAS28-dcrit 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-dcrit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-dcrit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-dcrit 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.

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