Background MIRAI (NCT01332994) investigated the early response to the IL-6 inhibitor tocilizumab (TCZ) within a homogeneous population of biological naïve patients (pts) with moderate/severe active RA who inadequately responded to traditional DMARDs; non-responders to TCZ subsequently received 1 cycle of rituximab (RTX; anti-CD20 therapy).
Objectives To assess the effects of TCZ and, if applicable, subsequent RTX treatment on PRO (SF-36, HAQ-DI, FACIT-F, VAS pain, disease activity; DA).
Methods MIRAI was a German, multicenter, two-arm, open-label, phase-IIIb-study. All pts received 4 TCZ infusions (8 mg/kg, q4w; 1st treatment period) until week 16. Partial responders (ΔDAS28>1.2 or DAS28≥2.6 and ≤3.2) received further 4 TCZ infusions; non-responders (ΔDAS28≤1.2 and DAS28>3.2) received subsequent RTX (1g each at week 16 and 18). All pts with a 2nd treatment period (TCZ or RTX) completed study at week 32. Besides the objective response measures based on the DAS28 and ACR core data set, efficacy assessments included PROs such as HAQ-DI, SF-36, FACIT-F (fatigue), patient's assessment of pain and DA (on a visual analogue scale; VAS).
Results A total of 519 pts received TCZ in the 1st treatment period (ITT-main). At week 16, 213 partial responders to TCZ entered a 2nd TCZ period (ITT-TCZ2), only 27 non-responder initiated subsequent RTX (ITT-RTX). At week 16, clinically meaningful mean improvements in HAQ-DI, SF-36, FACIT fatigue, pain and DA were noted in the ITT-main and in partial TCZ responders; further improvement in PRO was indicated under continued TCZ treatment, although mean changes from week 16 to week 32 were minor. Slight mean improvements in HAQ-DI, SF-36, FACIT fatigue and relevant mean improvements in VAS pain and DA, particularly after administration of RTX, were reported by TCZ non-responders; 9/27 non-responders achieved ΔHAQ-DI >0.22 at week 32 compared to week 16.
Conclusions Consistent with the data of clinical efficacy, the results of the PRO also indicated rapid onset of efficacy of initial TCZ treatment with most pronounced PRO improvements until week 16 and further benefit during continued TCZ in partial responders. In TCZ non-responders mean changes in PRO were less pronounced, although 1/3 of the TCZ non-responders achieved HAQ-DI response during subsequent RTX therapy.
Disclosure of Interest C. Iking-Konert: None declared, G.-R. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, BMS, Novartis, Medimmune, MSD, Pfizer, UCB, Roche, Speakers bureau: AbbVie, BMS, Novartis, MSD, Pfizer, UCB, Roche, T. Dörner: None declared, H. Schulze-Koops Consultant for: Roche, A. Rubbert-Roth: None declared, A. Engel: None declared, G. Gauler: None declared, R. Schwenke: None declared, M. Peters: None declared, H.-P. Tony Consultant for: AbbVie, Celgene, Chugai, Janssen, Lilly, MSD, Roche, Speakers bureau: AbbVie, Chugai, Roche