779 - Anti-Interleukin 17A Monoclonal Antibody Secukinumab Reduces Signs and Symptoms of Psoriatic Arthritis in a 24-Week Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial

Sunday, November 6, 2011: 3:00 PM
W470b (McCormick Place West)
I. McInnes1, J. Sieper2, J. Braun3, Paul Emery4, D. van der Heijde5, J. Isaacs6, G. Dahmen7, J. Wollenhaupt8, H. Schulze-Koops9, S. Gsteiger10, A. Bertolino11, W. Hueber11 and P. P. Tak12, 1University of Glasgow, Glasgow, United Kingdom, 2Charitè Campus Benjamin Franklin, Berlin, Germany, 3Rheumazentrum Ruhrgebiet, Herne, Germany, 4Chapel Allerton Hospital, Leeds, United Kingdom, 5Leiden University Medical Center, Leiden, Netherlands, 6Newcastle University and the Freeman Hospital, Newcastle-upon-Tyne, United Kingdom, 7Praxis fuer klinische Studien, Hamburg, Germany, 8Eilbeck Hospital, Hamburg, Germany, 9Klinikum Innenstadt der Ludwig-Maximilians-Universität, Munich, Germany, 10Novartis Pharma AG, Basel, Switzerland, 11Novartis Institutes for BioMedical Research, Basel, Switzerland, 12University of Amsterdam, Amsterdam, Netherlands
Presentation Number: 779

Background/Purpose: Interleukin 17A (IL-17A) is a novel target for the treatment of psoriatic arthritis (PsA). We assessed the safety and preliminary efficacy of secukinumab, an anti-IL-17A monoclonal antibody, in PsA.

Method: 42 patients with active PsA fulfilling CASPAR criteria were assigned 2:1 to receive two injections with secukinumab (10mg/kg) or placebo, given three weeks apart. The primary efficacy endpoint was the proportion of ACR20 responders at Week 6 in active compared with placebo recipients (one-sided p-value <0.1). As per protocol, no imputation was made for missing data (drop-outs were treated as missing).

Result: 25 (89%) patients on secukinumab and 10 (71%) on placebo completed the study. Five patients (4 secukinumab and 1 placebo) were excluded from the efficacy analysis due to protocol violations. Three (11%) of patients on secukinumab and 4 (29%) on placebo discontinued prematurely for lack of efficacy or withdrawal of consent. Demographics and baseline characteristics were balanced between groups for age, sex and parameters including mean (SD) SJC (secukinumab vs. placebo): 8.3 (5.6) vs. 9.5 (5.4); TJC 23.5 (19.4) vs. 22.6 (11.0); DAS28 4.8 (1.2) vs. 4.8 (1.2); MASES 3.0 (4.1) vs. 3.4 (2.3). Co-existing psoriasis, prior TNFi exposure and co-medication with DMARDS were present in 23 (98%), 11 (46%) and 21 (88%) patients on secukinumab and in 11 (89%), 5 (38%) and 10 (70%) on placebo, respectively. The ACR20 response rate at week 6 was 39% (9/23) on secukinumab vs. 23% (3/13) on placebo (P = 0.27). ACR20 response rates were 39% (9/23) vs. 15% (2/13) at week 12, and 43% (10/23) vs. 18% (2/11) at week 28 with secukinumab versus placebo, respectively. ACR50 and ACR70 response rates at week 6 on secukinumab vs. placebo were 17% vs. 8 % and 9% vs. 0%, respectively. CRP reductions at week 6 compared to baseline were observed on secukinumab (median [range] of 5.0 [0.3, 43.0] at baseline vs. 3.0 [0.2, 15.2] at week 6, but not on placebo (3.9 [1.3, 39.7] at baseline vs. 5.0 [0.8, 29.6] at week 6).  Similar reductions were seen for ESR, and reductions in acute phase parameters were maintained up to week 28. The overall rate of adverse events (AEs) was comparable in secukinumab versus placebo: 26 (94%) vs. 11 (79%). One severe adverse event (cellulitis hand) occurred on secukinumab, and was not suspected by the investigator to be study drug-related. 7 serious AEs were reported in 4 secukinumab patients (tendon rupture/carpal tunnel syndrome/cellulitis, obesity, fall, breast cancer [diagnosed prior to dosing and inclusion constituting a protocol violation]) and 1 with placebo (polyarthritis). Infections were reported in 16 (57%) patients on secukinumab and 7 (50%) patients on placebo.

Conclusion: The safety profile of secukinumab was favorable overall. Although the primary endpoint was not met, a substantial proportion of patients showed rapid and sustained improvements of clinical scores and acute phase parameters up to week 28. Trends towards a beneficial clinical effect support the rationale for larger clinical trials designed to assess clinical effectiveness.

Keywords: autoimmune diseases, clinical trials, interleukins (IL), monoclonal antibodies and psoriatic arthritis

Disclosure: I. McInnes, None; J. Sieper, None; J. Braun, None; P. Emery, None; D. van der Heijde, None; J. Isaacs, None; G. Dahmen, None; J. Wollenhaupt, None; H. Schulze-Koops, None; S. Gsteiger, Novartis Pharma AG, 3 ; A. Bertolino, Novartis Institutes for BioMedical Research, 3 ; W. Hueber, Novartis Institutes for BioMedical Research, 3 ; P. P. Tak, None.