Ixekizumab efficacy and safety with and without concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) in biologic DMARD (bDMARD)-naïve patients with active psoriatic arthritis (PsA): results from SPIRIT-P1

Abstract

Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239).

Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naïve use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed according to cDMARD status.

Results: Regardless of concomitant cDMARD usage, ACR20, ACR50 and ACR70 response rates were significantly higher versus placebo with IXEQ4W and IXEQ2W. The proportion of patients achieving HAQ-DI minimal clinically important difference was significantly higher versus placebo with IXEQ4W with concomitant cDMARD use and IXEQ2W, regardless of concomitant cDMARD use. Treatment-emergent adverse events (AE) were more frequent versus placebo for either ixekizumab-dosing regimen, regardless of concomitant cDMARD use. Serious AEs were not higher versus placebo, regardless of concomitant cDMARD use.

Conclusion: Ixekizumab treatment improved measures of disease activity and physical function in patients with active PsA relative to placebo, when used with or without concomitant cDMARD therapy.

Keywords: dmards (biologic); dmards (synthetic); methotrexate; psoriatic arthritis.

Conflict of interest statement

Competing interests: LCC: consultant for AbbVie, Celgene, Janssen, Sun Pharma, Pfizer, UCB, MSD, Novartis, Eli Lilly and Company, Amgen, BMS; grant/research support from AbbVie, Janssen. MK: consultant for Eli Lilly and Company. AG: consultant/advisory board agreements with Janssen, Celgene, Bristol Myers Squibb, Beiersdorf, AbbVie, UCB, Novartis, Incyte, Pfizer, Eli Lilly and Company, XenoPort, Crescendo Bioscience, Aclaris, Amicus, Reddy Labs, Valeant, Dermira, Allergan, CSL Behring, Merck, Sun Pharmaceutical Industries; research/educational grants from Janssen, Incyte. CLS, CHL and C-YL are employees and stockholders of Eli Lilly and Company. PJM: consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB Pharma, Sun; grant/research support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB Pharma, Sun; speakers bureau for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, UCB Pharma.

Figures

Figure 1

ACR response rates at 24 weeks in patients treated with PBO, IXEQ4W or IXEQ2W alone or in combination with cDMARDs or MTX. The proportions of patients achieving ACR20 (A), ACR50 (B) and ACR70 (C) are shown. The study was not designed to test equivalence or non-inferiority of treatment with ixekizumab alone versus treatment with ixekizumab in combination with cDMARDs. ACR20/50/70, 20%/50%/70% American College of Rheumatology response; cDMARD, conventional disease-modifying antirheumatic drugs; PBO, placebo; IXEQ4W, 80 mg ixekizumab once every 4 weeks; IXEQ2W, 80 mg ixekizumab once every 2 weeks; n, number of patients; MTX, methotrexate. *P

Figure 2

HAQ-DI change from baseline and proportion of patients achieving MCID after 24 weeks in patients treated with PBO, IXEQ4W or IXEQ2W alone or in combination with cDMARDs or MTX. (A) LSM changes from baseline of HAQ-DI. (B) Proportion of patients achieving MCID. The study was not designed to test equivalence or non-inferiority of ixekizumab alone versus treatment with ixekizumab in combination with cDMARDs. cDMARD, conventional disease-modifying antirheumatic drugs; HAQ-DI, Health Assessment Questionnaire-Disability Index; IXEQ2W, 80 mg ixekizumab once every 2 weeks; IXEQ4W, 80 mg ixekizumab once every 4 weeks; LSM, least squares mean; MCID, minimal clinically important difference; MTX, methotrexate; n, number of patients; PBO, placebo. *P