AB0944 Efficacy and safety of ixekizumab when used alone or in combination with conventional disease-modifying antirheumatic drugs (CDMARDS) in tnf-experienced patients with psoriatic arthritis

Background Registry studies 1,2 suggest that cDMARDs do not improve TNFi efficacy in the treatment of psoriatic arthritis (PsA), but studies of novel biologics are warranted. In SPIRIT-P2, TNFi-experienced patients with active PsA were treated with ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A. Objectives We conducted post-hoc analyses of SPIRIT-P2 data to investigate the efficacy and safety of IXE relative to placebo (PBO) when used alone or in combination with background MTX or cDMARDs in patients with PsA. Methods SPIRIT-P2 (NCT02349295) is a phase 3, multi-centre, randomised, double-blind, placebo-controlled trial of IXE in adults with active PsA and prior TNFi-inadequate response or intolerance. Patients were randomised 1:1:1 to receive PBO, 80 mg IXE either every 4 weeks (Q4W) or every 2 weeks (Q2W), after receiving a 160 mg initial IXE dose. Eligible established background cDMARD therapy was allowed in the double-blind treatment period (Week 0–24), but no changes were allowed unless for safety reasons or due to inadequate response at week 16. Efficacy and safety were assessed at week 24. Efficacy outcome measurements included ACR 20/50 responses, achievement of minimal disease activity (MDA), 28-joint disease activity score using CRP (DAS28-CRP), disease activity in psoriatic arthritis (DAPSA), and HAQ-DI. All comparisons were made relative to PBO by Fisher’s exact test for categorical end points and analysis of covariance models for continuous end points. Results At baseline, 185 (51%) patients received background cDMARDs. Of these patients, 149 received background MTX. ACR20, ACR50, and MDA response rates were significantly higher in patients treated with IXE versus PBO regardless of background cDMARD use (table 1). Disease activity improved significantly with IXE versus PBO in each subgroup, as measured by DAS28-CRP and DAPSA. Likewise, physical function improved with IXE versus PBO as indicated by significantly more profound decreases in HAQ-DI with IXEQ4W with or without background cDMARDs, and with IXEQ2W monotherapy. HAQ-DI improvements were significantly more profound versus PBO in patients treated with IXEQ4W with or without background cDMARDs, and with IXEQ2W monotherapy. Among IXE treated patients, higher proportions of patients achieved HAQ-DI MCID in all subgroups versus PBO, but these were only significantly higher in patients treated with IXEQ4W or IXEQ2W monotherapy. Regardless of background cDMARD use, efficacy outcomes were significantly improved with both IXE groups versus PBO, except for HAQ-DI for IXEQ2W in combination with cDMARDs and HAQ-DI MCID in all background cDMARD subgroups. The proportions of patients who experienced ≥1 treatment emergent adverse events (AE), serious AEs (including serious infections), or discontinuations due to AEs were comparable to the overall trial population. 3 Conclusions The efficacy of IXE versus PBO in PsA was similar in patients with or without background cDMARD use in this post hoc analysis with safety profiles comparable to the overall trial population. 3 References [1] Fagerli, et al. Ann Rheum Dis2014. [2] Mease et al. RMD Open 2015. [3] Nash et al. Lancet 2017. Disclosure of Interest P. Nash Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, F. Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Prophylix, Novartis, Iron4U, Consultant for: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Sanofi, Lilly, Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Sanofi, Lilly, Sandoz, A.-M. Orbai Grant/research support from: Abbvie, Celgene, Eli Lilly and Company, Horizon, Janssen, Novartis, Pfizer, Consultant for: Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB, S. Rathmann Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, D. Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, O. Benichou Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Deodhar Grant/research support from: Pfizer, Consultant for: Pfizer