Background/Purpose: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease affecting peripheral and axial joints. For patients with active psoriasis, the added burden of skin disease can further reduce the health-related quality of life (HRQoL) of patients with joint disease. The objective of this analysis is to determine the contribution of joint and skin improvements in the HRQoL of patients with active PsA during phase 3 clinical trials investigating ixekizumab (IXE) treatment.

Methods: The SPIRIT trials are double-blinded phase 3 trials investigating the treatment of IXE, a high affinity monoclonal antibody selectively targeting interleukin-17A, for patients with active PsA. The integrated database of 2 SPIRIT trials consisted of patients who were biologic DMARD-naive (SPIRIT-P1, NCT01695239) or were inadequate responders to TNF-inhibitors (SPIRIT-P2, NCT02349295). Patients were randomized to 80 mg IXE every 4 weeks (Q4W, N=229) or 2 weeks (Q2W, N=226) after a 160 mg starting dose or placebo (PBO, N=224). At baseline and Week 24, joint and skin disease were measured by the Disease Activity index for PSoriatic Arthritis (DAPSA; calculated post-hoc) and Psoriasis Area and Severity Index (PASI), respectively. HRQoL was measured by the EuroQoL 5 Dimensions Visual Analog Scale (EQ-5D VAS), Short Form-36 Health Survey (SF-36), and the Work Productivity and Activity Impairment-Specific Health Problem (WPAI).  The synergistic contribution of skin and joint improvements to HRQoL was modeled using smoothing spline method and depicted with response surface (Figure 1). Missing data were imputed using last observation carried forward.

Results: Of the 679 PBO- and IXE-treated patients in the SPIRIT trials, 402 (65%) and 224 (36%) patients had ≥3% body surface area (BSA) and ≥10% BSA psoriasis at baseline, respectively. In these patients, we applied response surface modeling to investigate the relationship between DAPSA, PASI, and change from baseline in EQ-5D VAS at Week 24. The greatest improvement in EQ-5D VAS was associated with the largest percent improvements in both DAPSA and PASI together, rather than DAPSA or PASI alone (Figure 2). Similar observations, regardless of ≥3% or ≥10% BSA baseline psoriasis, were made in domains of SF-36 (General Health, Physical Functioning, Social Functioning, and Vitality; data not shown) and WPAI (Activity Impairment; data not shown).

Conclusion: For PsA patients with psoriasis, optimal improvements in patients’ HRQoL, as measured by select domains of patient reported outcomes, were dependent on successful treatment of both joint and skin symptoms.