Background A key goal in rheumatoid arthritis (RA) therapy is to achieve remission or at least very low disease activity1. Secukinumab, a fully human anti-IL-17A monoclonal antibody has been shown to improve signs and symptoms of patients with active RA in this phase II trial2.
Objectives To report the effect of secukinumab treatment on disease activity in patients with active RA despite stable methotrexate (MTX) treatment.
Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). At wk20, all placebo patients were switched to secukinumab 150mg. All patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16. Secondary efficacy endpoints are presented here using ACR50, Health Assessment Questionnaire (HAQ-DI) and EULAR remission rate (DAS28-CRP≤2.6).
Results Demographics and baseline characteristics were comparable across treatment groups. The primary endpoint ACR 20 at wk16 was not achieved. ACR50 responses at wk24 and wk52 were highest in patients who remained on secukinumab 150mg for the entire study (ACR50: wk24=50%; wk52=55%). HAQ scores improved over time in responders on secukinumab 150mg (wk24=-0.6; wk52=-0.8). At wk16, the proportion of patients achieving EULAR remission response was 11.3% for 25mg, 6.1% for 75mg, 11.6% for 150mg, 14.6% for 300mg and 6% for placebo. The percentage of patients achieving EULAR remission increased overtime and were highest in patients on secukinumab 150mg (wk24=30%, wk52=40%). Additionally, patients who responded on placebo but switched to secukinumab 150mg at wk20 achieved similar EULAR remission rates that patients receiving secukinumab 150mg for the entire study (wk24=29.4%; wk52=38.9%). Non-responders did not gain much additional efficacy benefit after dose escalation as assessed by ACR50, HAQ and EULAR remission criteria. The safety data for this cohort has been previously described2. Overall rates of adverse events (AEs) at wk52 was comparable to data up to wk20 and most AEs were mild to moderate in severity and did not lead to study discontinuation.
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.
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Genovese M., et al. Arthritis Rheum. 2011;63(10[suppl]):S149–S150.
Disclosure of Interest M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, P. Durez: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG