RT Journal Article
SR Electronic
T1 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
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.160146
DO 10.3899/jrheum.160146
A1 Nemanja Damjanov
A1 Malgorzata Tlustochowicz
A1 Jacob Aelion
A1 Maria Greenwald
A1 Annette Diehl
A1 Indranil Bhattacharya
A1 Elena Peeva
A1 Sandeep Menon
A1 Ian Gourley
YR 2016
UL http://www.jrheum.org/content/early/2016/09/27/jrheum.160146.abstract
AB 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 α 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.