Final SPIRIT-H2H data still favour ixekizumab for biologic-naïve PsA patients

The final 1-year results from the SPIRIT-H2H* trial ixekizumab (IXE) remains superior to adalimumab (ADA) for treating biologic-naïve patients with psoriatic arthritis (PsA).

In the initial report, SPIRIT-H2H met the primary endpoint at week 24 by demonstrating the superiority of IXE over ADA for the simultaneous achievement of a 50-percent improvement on the American College of Rheumatology (ACR) criteria and complete clearance on the Psoriasis Area and Severity Index (PASI), the investigators said. [Ann Rheum Dis 2020;79:123-131]

IXE held onto its position as the better biologic disease-modifying antirheumatic drug (bDMARD) through 52 weeks, with significantly higher proportions of patients both showing ACR50 and PASI100 responses compared with ADA (39 percent vs 26 percent; p<0.001). When assessed separately, results for PASI100 remained in favour of the former (64 percent vs 41 percent; p<0.001), but there was no between-group difference seen for ACR50 (49.8 percent vs 49.8 percent; p=0.924). [Ann Rheum Dis 2020;doi:10.1136/annrheumdis-2020-217372]

“Importantly, response rates for IXE were consistent irrespective of concomitant conventional synthetic (cs)DMARD use, while numerically higher response rates for ADA were seen when used in combination with csDMARDs than in monotherapy,” the investigators noted.

Similar performances were observed for ACR20/50/70 responses, PsA-specific composite disease activity measures, enthesitis and dactylitis resolution, as well as physical function outcomes. However, IXE had a faster onset of action, with greater efficacy on the skin and nail.

Out of the 566 patients (average age, 48 years; 55.1 percent male; 11 percent Asian) randomized equally between the two biologic drugs, 246 (87 percent) patients treated with IXE and 237 (84 percent) treated with ADA completed the 52-week follow-up.

Concomitant csDMARD use (baseline: 193 and 199 patients in the IXE and ADA arms, respectively) had been stable in most of the patients over 52 weeks, except for three patients discontinuing methotrexate (MTX; two ADA, one IXE) and seven patients adjusting MTX dose (three ADA, four IXE) after week 24.

“Overall, the safety profiles of both drugs were consistent with previous clinical trials and the regulatory labels. However, [there are] a number of numerical differences,” according to the investigators.

For the most part, although IXE treatment resulted in more treatment-emergent adverse events (TEAEs), the majority of these were mild and moderate in severity, whereas more severe TEAEs and serious AEs were observed with ADA. The latter was also associated with slightly higher frequencies of infections and treatment discontinuations due to AEs.

Meanwhile, injection site reactions were higher in the IXE arm. One patient in the same treatment arm developed Crohn’s disease.

Despite the presence of limitations, “SPIRIT-H2H study comparing ixekizumab versus adalimumab is the first fully disclosed direct head-to-head study in PsA; its findings over 52 weeks will inform future treatment recommendations and may impact selection of therapy in bio-naïve patients with active PsA,” the investigators concluded.