Secukinumab Efficacy in TNFi-Naïve & Exposed PsA Patients Compared

Post-hoc data analysis from a phase 3 trial evaluating the efficacy of secukinumab in psoriatic arthritis (PsA) has found that both subcutaneous (SC) doses of 300 mg and 150 mg provided sustained improvements in the signs and symptoms of PsA in tumor necrosis factor inhibitor (TNFi)-naïve patients.¹ 

In patients who had received a TNFi in the past, the 300 mg dose remained effective in patients ≥90 kg receiving concomitant methotrexate (MTX) therapy with lower baseline disease activities.¹ These findings were recently reported in the Journal of Rheumatology.

Secukinumab, an anti-interleukin(IL)-17A monoclonal antibody, was previously shown to improve PsA disease activity, physical function, and quality of life in the first year after initiation.²  Subsequent post-hoc analysis was done to assess if there were differential results in TNFi-exposed or naïve patients.

Data was analyzed post-hoc from the phase 3 trial “Efficacy at 24-Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis (FUTURE-2, ClinicalTrials.gov Identifier NCT01752634). 

Briefly, the proportion of patients with active PsA fulfilling the Classification criteria for Psoriatic Arthritis (CASPAR) who achieved an American College of Rheumatology 20 (ACR20) was measured after receiving either secukinumab  300mg, 150mg, 75mg (weekly for 4 weeks followed by monthly dosing starting at Week 4), or placebo in a blinded fashion.  Concomitant MTX doses of ≤ 25 mg per week was permitted in the study.

TNFi-naïve patients (n=258) had a 58.2% ACR20 response rate at week 24 after receiving secukinumab 300mg (P<.001), 63.5% after  receiving secukinumab 150mg (P<.001), and 36.9% after receiving secukinumab 75mg  (P<.001). This is compared to a 15.9% ACR20 response rate found in the placebo group.

In TNFi-exposed patients (n=139)  ACR response rates at 24 weeks were less than in the ACR-naïve group. The ACR20 response rate for TNFi-exposed patients was 45.5% for those receiving secukinumab 300 mg  (P<.001), 29.7% for those receiving secukinumab 150 mg  (P<.001), and 14.7% for those receiving secukinumab 75mg (P<.001).  This was compared to the ACR20 response rate of 14.3% in the placebo group.

At study conclusion 52 weeks post-randomization, ACR20 response rates in TNFi-naïve patients treated with secukinumab 300 mg, 150 mg, and 75 mg were 68.7%, 79.4%, and 58.5%, respectively. These are in comparison to ACR20 response rates with secukinumab 300 mg, 150 mg, and 75 mg were 54.5%, 37.8%, and 35.3% in TNFi-exposed patients.

“These data suggest that secukinumab 150 mg appears to be the most appropriate dose for TNFi-naive patients, but among the TNFi-exposed patients, the 300 mg dose seems to be more appropriate, especially among those patients with high levels of disease activity,” the study authors stated.

Summary and Clinical Applicability

Greater ACR20 improvements were found in TNFi-naïve patients as compared to TNFi-exposed patients treated with secukinumab for active PsA. Certain TNFi-exposed patients still benefited from secukinumab 300 mg doses. 

“Targeting IL-17A with secukinumab may be a viable treatment option for patients with PsA, including those previously treated with TNFi,” the study authors concluded.

Limitations and Disclosures

Subgroup analysis was performed post-hoc and was, therefore, prone to multiplicity.  Subgroups also included a smaller number of patients.

This study and several of its authors received support from secukinumab (Cosentyx©) manufacturer Novartis Pharmaceuticals Corp. 

Reference

1. Kavanaugh A, McInnes IB, Mease PJ, et al. Efficacy of Subcutaneous Secukinumab in Patients with Active Psoriatic Arthritis Stratified by Prior Tumor Necrosis Factor Inhibitor Use: Results from the Randomized Placebo-controlled FUTURE 2 Study. J Rheum. Published online ahead of print June 15 2016; doi:10.3899/ jrheum.160275

2.     McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015;386:1137-46.