Secukinumab (an Anti-Il17a Monoclonal Antibody) at EULAR 2012

Is secukinumab (AIN457), an anti-IL17A monoclonal antibody, still being studied?


Yes, secukinumab is under scrutiny. M. Genovese and colleagues presented a study, in which secukinumab has been studied patients with rheumatoid arthritis, still active despite methotrexate therapy. “Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16.” This endpoint hasn’t been achieved.


[THU0111] SECUKINUMAB TREATMENT IMPROVES ACR50, HAQ-DI AND EULAR REMISSION RATES IN PATIENTS WITH RHEUMATOID ARTHRITIS
M. Genovese1, H. Kellner2, P. Durez3, C.E. Codding4, G. Ligozio5, H.B. Richards6, C. Escrig6, S. Mpofu6. 1Stanford University, Palo Alto, United States; 2Centre for Inflammatory Joint Diseases, Munich, Germany; 3Université Catholique de Louvain, Brussels, Belgium; 4Health Research of Oklahoma, Oklahoma; 5Novartis Pharmaceuticals Corporation, East Hannover, United States; 6Novartis Pharma AG, Basel, Switzerland
Conclusions: The primary efficacy endpoint was not achieved in this study. Analysis of secondary endpoints suggest that a substantial proportion of patients achieved a consistent ACR50, HAQ-DI and EULAR remission rates improvements through Wk52 in patients with active RA despite stable MTX treatmentwho either remained on or escalated to secukinumab 150mg were observed. These results provide potential evidence for the role of secukinumab in the treatment of RA and support further exploration of secukinumab in RA.


The rest of the studies presented at EULAR 2012 aren’t giving us much more. Secukinumab doesn’t change the lipid profile or the atherogenic risk in patients with rheumatoid arthritis. Fatigue improves and the last study concludes that phase 3 studies should focus on 75 and 150 mgs.


[THU0119] LACK OF EFFECT OF SECUKINUMAB TREATMENT ON THE LIPID PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II STUDY
P. Durez1, M. Genovese2, H. Kellner3, C. Codding4, G. Ligozio5, H. Richards6, C. Escrig6, S. Mpofu6. 1Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium; 2Stanford University, California, United States; 3Centre for Inflammatory Joint Diseases, Munich, Germany; 4Health Research of Oklahoma, Oklahoma; 5Novartis Pharmaceuticals Corporation, East Hanover, United States; 6Novartis Pharma AG, Basel, Switzerland
Conclusions: Treatment with secukinumab was not associated with changes in the lipid profile or the atherogenic risk in patients with RA.


[AB0506] ENHANCED IMPROVEMENT IN FATIGUE FROM RA TREATMENT WITH SECUKINUMAB: AN APPLICATION OF IRT METHODOLOGY
A. Gnanasakthy1, M. Kosinski2, P. Durez3, U. Mallya1, S. Mpofu4. 1Novartis Pharmaceuticals Corporation, East Hanover; 2QualityMetric Incorporated, Lincoln, RI, United States; 3Université Catholique de Louvain, Brussels, Belgium; 4Novartis Pharma AG, Basel, Switzerland
Conclusions: IRT methods offer a promising approach to improving the measurement of fatigue in treatment studies of RA.


[AB0504] ASSOCIATION BETWEEN HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND ACR IMPROVEMENT AMONG RHEUMATOID ARTHRITIS (RA) PATIENTS TREATED WITH SECUKINUMAB
A. Gnanasakthy1, M. Kosinski2, M. Genovese3, U. Mallya1, S. Mpofu4. 1Novartis Pharmaceuticals Corporation, East Hanover; 2QualityMetric Incorporated, Lincoln, RI; 3Stanford University School of Medicine, California, United States; 4Novartis Pharma AG, Basel, Switzerland
Conclusions: In patients on secukinumab with greater ACR responses there were associated relevant benefits in the patients overall physical, social, role functioning, and psychological well-being.


[AB0582] IMPROVEMENTS IN HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) RECEIVING SECUKINUMAB: RESULTS OF A DOSE-FINDING STUDY
V. Strand1, M. Genovese1, U. Mallya2, H. Richards3, S. Mpofu3. 1Stanford University School of Medicine, California; 2Novartis Pharmaceuticals Corporation, East Hanover, United States; 3Novartis Pharma AG, Basel, Switzerland
Conclusions: A dose response in reported improvements in HRQoL was evident with 75mg and 150mg, exceeding those observed with 25mg, 300mg and placebo. From an HRQoL perspective, these findings support the selection of secukinumab 75mg and 150mg doses for future phase 3 RCTs in RA.


All in all these studies and secukinumab leave me a bit disappointed. I still hope, that the drug could be useful as we still lack different modes of action to change therapies that aren’t working for our patients. I’m looking forward to the next meetings.

Other blogpost on Secukinumab include:

http://rheumatologe.blogspot.de/2011/11/anti-il17a-monoclonal-antibody.html 
http://rheumatologe.blogspot.de/2011/11/secukinumab-to-treat-rheumatoid.html