A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate
- 1Division of Rheumatology Research, Swedish Medical Center and University of Washington, Seattle, Washington, USA
- 2Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA
- 3Department of Clinical Pharmacology, V Tsitlanadze Scientifically-Practical Rheumatology Center Tbilisi, Georgia
- 4Rheumatology Clinic, Institute of Rehabilitation and Treatment Niska Banja, Serbia
- 5Internal Disease Dept, State Institute of Healthcare, Kemerovo, Russian Federation
- 6Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey, USA
- 7Global Clinical Research, Bristol-Myers Squibb, Princeton, NJ
- 8Alder Biopharmaceuticals Inc, Bothell, Washington, USA
- Correspondence to Philip J Mease, Department of Rheumatology, Seattle Rheumatology Associates, 1101 Madison Street Ste 1000, Seattle 98104, Washington, USA;
Contributors PM contibuted to the design of the trial, analysis and interpretation of the data, and supervised the development of the manuscript. VS contributed to the design of the trial, analyis and interpretation of the data—specifically, the HR-QoL data, and contributed to the development of the manuscript. LS, AD and TR supervised the collection of data at their respective sites, participated in the analysis of the data and reviewed the manuscript for content. L-AX and YL participated in data analysis and in the development of the manuscipt. JS contributed to the design of the trial, analyis and interpretation of the data and contributed to the development of the manuscript. All authors reviewed and approved the final submitted version of the manuscript.
- Received 16 November 2011
- Accepted 11 December 2011
- Published Online First 10 February 2012
Background Interleukin 6 (IL-6) plays a key role in the inflammatory cascade in rheumatoid arthritis. BMS945429 is a humanised, monoclonal antibody that potently binds IL-6.
Objective To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate.
Methods Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28).
Results Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p<0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p<0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score <2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity.
Conclusions In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.
Funding Alder Biopharmaceuticals and Bristol-Myers Squibb.
Competing interests PM has received research grants from, or served as a consultant to, Abbott, Amgen, BiogenIdec, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Novartis, Pfizer and UCB. PM has served on speaker's bureaus for all of the above except Novartis.
Provenance and peer review Not commissioned; externally peer reviewed