Safety and Efficacy of SBI 087, a Subcutaneous Agent for B Cell Depletion, in Patients with Active Rheumatoid Arthritis: Results from a Phase II Randomized, Double blind, Placebo controlled Study
Objective. To evaluate subcutaneous SBI 087 to treat rheumatoid arthritis (RA) Methods. A total of 210 adult patients with active RA were randomized to receive either 200 mg SBI 087 or placebo (Pbo) according to one of these patterns: SBI/Pbo/Pbo (SBI on Day 1) SBI/SBI/Pbo (SBI days 1 and 15) SBI/Pbo/SBI (SBI days 1 and 84) SBI/SBI/SBI (SBI days 1, 15, and 84) or Pbo/Pbo/Pbo (Pbo all 3 days) All patients were seropositive and taking background methotrexate. The primary endpoint was proportion of patients achieving 20% improvement from baseline at Week 16 by American College of Rheumatology criteria (ACR20) Other outcomes included 28 joint Disease Activity Score (DAS28) C reactive protein (CRP) physician's and patient's global assessments of disease activity (PGA and PtGA, respectively) and Health Assessment Questionnaire Disability Index (HAQ DI) Peripheral CD19+ B cells were measured by high sensitivity flow cytometer. Statistical significance was set at 2 sided a 0.10 level. Results. The SBI/SBI/SBI group demonstrated significant improvement in ACR20 and DAS28 CRP from Week 8 onward, sustained improvement in CRP levels from Week 12 onward, and significant improvements in PGA and PtGA in weeks 16 through 24, and in HAQ DI at Week 24. The SBI/Pbo/Pbo and SBI/SBI/Pbo groups did not meet the primary endpoint but demonstrated improvements in several secondary endpoints. All treatment groups exhibited depletion of peripheral CD19+ B cells throughout the study. Overall, 61.5% of patients receiving SBI 087 and 55.0% of patients receiving Pbo reported adverse events. Conclusion. SBI 087 effectively depleted peripheral CD20 B cells and was well tolerated. Improvements were consistently observed in the SBI/SBI/SBI group for the majority of efficacy and quality of life outcomes.
The Journal of Rheumatology