Background/Purpose: PsA is a highly heterogeneous chronic inflammatory disease combining a range of musculoskeletal and extra-articular manifestations. Ixekizumab (IXE) is approved for the treatment of moderate to severe psoriasis and more recently for active PsA. This post-hoc analysis describes the efficacy of IXE at week 24 in different phenotypes of PsA patients.

Methods: Biologic naïve patients (SPIRIT-P1) were randomized to IXE 80 mg (initial dose 160mg) every 4 (Q4W; N=107) or 2 weeks (Q2W; N=103), to adalimumab 40 mg (Q2W; N=101), or to placebo (PBO; N=106). Patients who had an inadequate response or intolerance to TNF inhibitors (SPIRIT-P2) were randomized to IXE Q4W (N=122) or Q2W (N=123), or to PBO (N=118). Patients fulfilled the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria and had active disease with ≥3TSJ and 3≥SJC. Patients were classified according to the following phenotypes of PsA¹: polyarthritis (≥5TJC and/or ≥5SJC), oligoarthritis (<5TJC and <5SJC), DIP joint only, enthesitis and dactylitis according to either the investigator’s judgment or a scale-based definition. In each phenotype ACR 20, 50 and 70 response criteria, Minimal Disease Activity Psoriasis Area Severity Index (MDA_PASI), and Disease Activity Psoriatic Arthritis (DAPSA) remission and low disease activity (LDA) response criteria were assessed to evaluate IXE effect at week 24 combining both doses. For each phenotype with a sufficient sample size, the IXE- and PBO-treated patients’ baseline characteristics were assessed. Treatment effects of IXE and PBO were compared using Chi-square tests (or Fisher’s exact tests if appropriate) within each phenotype.

Results: The most frequent phenotypes were: polyarthritis (N=662), enthesitis (investigator: N=459; LEI>0: N=403), and dactylitis (investigator: N=220; LDI-B>0: N=155). Too small sample sizes due to inclusion criteria^2,3 or low frequency were observed for “DIP joint only”, oligoarthritis and arthritis mutilans phenotypes (N=22, N=17 and N= 15; respectively). Baseline patient characteristics were generally balanced between treatment arms and similar between the 3 most frequent phenotypes, with no difference in disease activity and duration. Efficacy of IXE was consistent across the different phenotypes for various outcomes at week 24: ACR20/50/70, MDA_PASI, DAPSA remission and DAPSA-LDA in SPIRIT trials irrespective of previous biologic DMARD use (Tab.1). Response rates were consistent to overall efficacy reported with IXE in SPIRIT trials^2-4.

Conclusion: Treatment responses with IXE at week 24 were consistent regardless of the phenotypes.

References:

¹Moll JM, Wright V. Semin Arthritis Rheum. 1973;3:55-78

²Mease PJ, et al. Ann Rheum Dis. 2017;76:79-87

³Nash P, et al. Lancet. 2017;389:2317-2327

⁴Gladman DD, et al. EULAR18-2325 (SAT0321) abstract accepted, Ann Rheum Dis.