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Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study


Rheumatol Ther. 2020 Dec;7(4):1021-1035. doi: 10.1007/s40744-020-00250-3.Epub 2020 Nov 16.

Josef S Smolen 1Anthony Sebba 2Eric M Ruderman 3Hendrik Schulze-Koops 4Christophe Sapin 5Amanda M Gellett 5Aubrey Trevelin Sprabery 5Lingnan Li 5Inmaculada de la Torre 5Gaia Gallo 5Soyi Liu-Leage 5Sreekumar Pillai 5Paulo Reis 5Peter Nash 6

Author Information

1 Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

2 Arthritis Associates, Palm Harbor, FL, USA.

3 Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

4 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians University of Munich, Munich, Germany.

5 Eli Lilly and Company, Indianapolis, IN, USA.

6 School of Medicine, Griffith University, Brisbane, QLD, Australia. drpnash@tpg.com.au.


Introduction: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA.

Methods: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher's exact test. Missing data were imputed using non-responder imputation.

Results: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use.

Conclusion: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.