Background Clazakizumab (CLZ) is a potent, neutralizing anti-interleukin-6 (IL-6) monoclonal antibody currently in development for RA. The Phase IIb study described herein evaluated the efficacy and safety of subcutaneous (SC) CLZ with or without MTX in patients with moderate-to-severe RA and an inadequate response to MTX in a randomized, comparator-controlled, double-blind study.1
Objectives To compare the change from baseline at Weeks 12 and 24, and the proportion of patients achieving minimal clinically important differences (MCID) at Week 24, in patient-reported outcomes (PROs) on treatment with CLZ with and without MTX vs MTX alone.
Methods This was a post hoc analysis of data from the Phase IIb study. Patients were randomized equally to receive either CLZ 25, 100, or 200 mg with MTX, CLZ 100 or 200 mg monotherapy, or MTX alone every 4 weeks or adalimumab with MTX every 2 weeks. PROs assessed included the Health Assessment Questionnaire-Disability Index (HAQ-DI); fatigue (visual analogue scale [VAS]), pain (VAS), Patient Global Assessment (PGA) of disease activity (VAS); and the physical component summary (PCS) and mental component summary (MCS) of the Short Form 36-item questionnaire (SF-36). HAQ-DI was previously reported.1 Analyses were conducted on the modified intent-to-treat population comprising all randomized patients who received at least one dose of study medication. MCIDs for each PRO were based on criteria from the literature. An analysis of covariance was conducted with treatment as a factor and baseline scores as covariates. In cases where patients received rescue medication, or with missing data, a last observation carried forward approach was used.
Results Overall, 418 patients were randomized. Compared with MTX alone, treatment with CLZ with or without MTX (at all doses) resulted in greater mean changes from baseline, and higher proportions of patients achieving an MCID on each of the PROs assessed at Week 24, except MCS (Table).
Conclusions Treatment with clazakizumab with or without MTX resulted in improvements in multiple PROs and a greater proportion of patients achieved MCID on these PROs compared with MTX alone in patients with RA with an inadequate response to MTX.
Weinblatt M et al. Arthritis Rheum 2013;65(10):S735–36.
Disclosure of Interest E. Alemao Shareholder of: BMS, Employee of: BMS, S. Joo Shareholder of: BMS, Employee of: BMS, S. Banerjee Shareholder of: BMS, Employee of: BMS, P. Emery Grant/research support: AbbVie, BMS, Merck, Pfizer, Roche, Consultant for: AbbVie, BMS, Merck, Pfizer, Roche, Takeda, M. Weinblatt Grant/research support: BMS, Crescendo Bioscience, UCB, Consultant for: BMS, Crescendo Bioscience, UCB, AbbVie, Roche, Janssen, G. L'Italien Shareholder of: BMS, Employee of: BMS