The selective interleukin-17A inhibitor ixekizumab (IXE) is approved for the treatment of active psoriatic arthritis (PsA) and moderate-to-severe plaque psoriasis (PsO). The SPIRIT-H2H study evaluated the efficacy and safety of IXE versus adalimumab (ADA), another biologic disease-modifying antirheumatic drug (bDMARD), approved in patients with PsA and PsO. [1]

• This post-hoc subgroup analysis evaluated various 24-week efficacy outcomes from SPIRIT-H2H in patients with high or low PsO body surface area (BSA) involvement at baseline.

Type of study, patients, and inclusion criteria

• SPIRIT-H2H was a multicentre, open-label, rater-blinded, parallel-group study in which bDMARD-naïve patients (N=566) with PsA and active PsO (≥3% BSA involvement) were randomised to IXE or ADA for 52 weeks.
• Dosing was based on the baseline severity of PsO:
  • Moderate-to-severe PsO was defined as PASI score ≥12, sPGA ≥3 and BSA involvement ≥10%.
  • Patients with moderate-to-severe PsO received:
    • IXE (160 mg at week 0, 80 mg Q2W up to week 12 then Q4W). or
    • ADA (80 mg at week 0, 40 mg Q2W starting at week 1).

• Patients not fulfilling the criteria for moderate-to-severe PsO received:
  • IXE (160 mg at week 0, 80 mg Q4W), or
  • ADA (40 mg at week 0, 40 mg Q2W),

Primary outcome measure

• The primary endpoint was the proportion of patients achieving simultaneous improvement of ≥50% in American College of Rheumatology criteria (ACR50) and 100% in PASI score (PASI100) at week 24.
• In this post-hoc subgroup analysis, efficacy outcomes at week 24 were compared between IXE and ADA in patients with baseline BSA involvement of ≥10% or <10%.

• At baseline, patients with BSA ≥10% (n=217) consistently showed higher arthritis- and skin-related clinical assessment scores, and worse patient-reported outcomes, than patients with BSA <10% (n=349).
• With regards to the simultaneous achievement of ACR50 and PASI100 at week 24, consistent response rates across baseline BSA levels were observed among IXE-treated patients (37.2%, and 35.3% for high and low BSA, respectively) (Figure).
• Among ADA-treated patients, a lower response rate was observed in the high compared to the low BSA subgroup (21.2% vs 31.8%), resulting in a significant difference versus IXE.
• PASI100 and PASI90 responses were significantly higher for IXE than ADA in both subgroups.
• By contrast, PASI75 responses were significantly higher for IXE only in the subgroup with BSA <10%.
• For ACR50, responses were similar for IXE versus ADA in both subgroups. Remission rates based on Disease Activity in Psoriatic Arthritis scores and Minimal Disease Activity (MDA6) were significantly higher for IXE than ADA in the BSA ≥10% subgroup.
• Dermatology Life Quality Index (0,1) responses were also significantly higher for IXE than ADA in the BSA ≥10% subgroup.

• IXE was associated with higher levels of response than ADA for skin and joint outcomes in bDMARD-naïve patients with active PsA and concomitant PsO, regardless of BSA involvement at baseline.
• For patients with ≥10% BSA involvement, IXE was associated with a statistically significant better efficacy outcome than ADA with respect to the primary endpoint.
• Data from this post-hoc analysis are consistent with the findings of the SPIRIT-H2H study.