Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
One Year Efficacy and Safety Results of a Phase II Trial of Secukinumab in Patients with Rheumatoid Arthritis.
Genovese1, Mark C., Durez2, Patrick, Richards3, Hanno B., Supronik4, Jerzy, Dokoupilova5, Eva, Aelion6, Jacob A., Lee7, Sang-Heon
Stanford University, Palo Alto, CA
KobeKonan Yamate Clinic, Kobe, Japan
Novartis Pharmaceuticals Corporation, East Hanover, NJ
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
Novartis Pharma AG, Basel, Switzerland
NZOZ Centrum Medyczne Artur Racewicz, Bialystok, Poland
Medical Plus s.r.o, Uherske Hradiste, Czech Republic
Arthritis Clinic, Jackson, TN
Konkuk University Medical Center, Seoul, South Korea
Health Research of Oklahoma, Oklahoma City, OK
Centre for Inflammatory Joint Diseases, Munich, Germany
To assess the efficacy and safety of secukinumab (AIN457) in patients with active rheumatoid arthritis (RA) despite stable methotrexate (MTX) up to Week 52.
Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at Week 16. After Week 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at Week 20 (except patients dosed initially on 300mg who remained on the same dose). All placebo patients were switched to secukinumab 150mg. Patients were followed through Week 52.
Demographics and baseline characteristics were comparable across all groups. ACR20 responder rates at Week 16 were higher with secukinumab 75mg, 150mg and 300mg (47%, 47% and 54%, respectively) vs placebo (36%) but did not reach statistical significance.
Responders on secukinumab maintained their ACR20 response from Week 24 to 52. Improvement in ACR20 response rates at weeks 24 and 52 were seen in patients who remained on secukinumab 150mg for the entire study [15/20 (75%) and 18/20 (90%), respectively]. Through Week 52, responders who remained on secukinumab 150mg had further improvement in ACR50 and ACR70 with the highest increases seen in ACR70 [4/20 (20%) and 8/20 (40%) at weeks 24 and 52, respectively] as did responders who switched from placebo to secukinumab 150mg [1/18 (6%) and 4/18 (22%) at weeks 24 and 52, respectively] (Figure 1).
Figure 1. ACR20, ACR50 and ACR70 response rates in Week-16 responders at weeks 24 and 52.
DAS28-CRP reductions were sustained up to Week 52 in responders. Responders who remained on secukinumab 150mg had improvement in HAQ scores (-0.6 at Week 24 vs-0.8 at Week 52). Non-responders did not gain much additional efficacy benefit after dose escalation as assessed by ACR20/50/70 and DAS28-CRP. The overall rates of AEs at Week 52 remained comparable to data seen at Week 20 (6070%) and most AEs were mild to moderate in severity and did not lead to study discontinuation (6.9%). The rate of infections was 31.9% overall. Twenty one (9.7%) SAEs were reported including 6 cases of serious infections without dose relationship. There were 3 malignancies and no deaths up to Week 52.
The primary efficacy endpoint was not achieved in this trial possibly due to an unexplained increase in ACR20 in the placebo group between weeks 12 (24%) and 16 (36%). However, ACR20-responders at Week 16 experienced maintenance or improvement of efficacy through Week 52 with highest efficacy in patients who remained on 150mg throughout the trial. Patients on secukinumab who were non-responders at Week 16 did not gain much additional efficacy benefit after dose escalation. Secukinumab was well tolerated and the rate and frequency of AEs remained stable over time without unexpected safety findings.
To cite this abstract, please use the following information:
Genovese, Mark C., Durez, Patrick, Richards, Hanno B., Supronik, Jerzy, Dokoupilova, Eva, Aelion, Jacob A., et al; One Year Efficacy and Safety Results of a Phase II Trial of Secukinumab in Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :401