In bDMARD-naïve patients with PsA and active plaque PsO, ixekizumab and adalimumab showed comparable efficacy at Week 24 in terms of percentage of patients achieving ≥50% or ≥70% improvement in clinical components, and in patient-reported outcomes of the ACR composite measure.
Head-to-head studies may provide valuable guidance to physicians in selecting optimal treatment and allow to formulate more precise evidence-based treatment guidelines.  Ixekizumab is a high-affinity monoclonal antibody selectively targeting interleukin-17A  that is approved for the treatment of moderate-to-severe plaque psoriasis (PsO), active psoriatic arthritis (PsA), and active ankylosing spondylitis. [3,4] SPIRIT-H2H is the first head-to-head (H2H) superiority trial in active PsA, which demonstrated the superiority of ixekizumab over adalimumab on a combined endpoint at Week 24. 
To assess and compare the individual American College of Rheumatology (ACR) components (tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP), HAQ-Disability Index (HAQ-DI), joint pain by visual analog scale (VAS), physician and patient global assessment) at Week 24 of ixekizumab and adalimumab treatment arms (SPIRIT-H2H trial).
An open-label study design with blinded outcome assessments was chosen to reduce the heavy burden of placebo injections on patients.
To be qualified as blinded assessor, physicians were required to have a minimum of 1 year of experience in TJC and SJC.
A total of 566 patients were randomized to receive either ixekizumab (n=283) or adalimumab (n=283) and followed up for 24 weeks.
The starting dose of ixekizumab was 160 mg at week 0. Pateints with moderate-to-severe plaque psoriasis were treated with ixekizumab Q2W from Weeks 2 to 12, and ixekizumab Q4W thereafter (N=65); participants not meeting criteria for moderate-to-severe plaque psoriasis were treated with ixekizumab Q4W from Week 4 (N=218).
For adalimumab, the starting dose at week 0 was 80 mg in patients with moderate-to-severe plaque psoriasis (N=64), or 40 mg in those not meeting criteria for moderate-to-severe plaque psoriasis (N=219); the maintenance dose was 40 mg every 2 weeks.
The primary outcome was the percentage of pts meeting ≥50% or ≥70% improvement in each ACR component at Week 24
Main inclusion criteria
PsA lasting for at least 6 months and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) criteria.
Active PsA (≥3/68 tender and ≥3/66 swollen joints at screening and baseline).
Active plaque psoriasis (body surface area ≥3% at screening and baseline).
Inadequate response to ≥1 conventional synthetic disease modifying anti-rheumatic drug (csDMARD).
In bDMARD-naïve patients with PsA and active plaque psoriasis, ixekizumab and adalimumab had comparable efficacy at Week 24 across ACR components as determined by the percentage of patients achieving ≥50% or ≥70% improvement in clinical components, and in patient-reported outcomes of the ACR composite measure.
Key messages/Clinical perspectives
This study provides important information with regard to the selection among different biologic DMARDs in active PsA.