Results of direct comparison of the clinical efficacy of ixekizumab and adalimumab: data from the SPIRIT H2H study

Abstract

Objective: to analyze the data available in the literature on the efficacy and safety of ixekizumab (IXE) and adalimumab (ADA) via their direct comparisons in the treatment of psoriatic arthritis (PsA).Patients and methods. The results of the SPIRIT H2H study were analyzed, the aim of which was to investigate the potential superiority of IXE to ADA for arthritis and skin manifestations in a group of patients with active PsA, stable plaque psoriasis with an inadequate response to synthetic disease-modifying antirheumatic drugs (sDMARDs) who had not previously received biological agents (BAs).Design: a 52-week multicenter, randomized, parallel-group study. The patients were randomized 1:1 to open IXE or ADA administration groups for 52 weeks. This review presents the data obtained at 24-week follow-up.Of the 684 screened patients, 566 (82.7%) were included in the study; moreover, the distribution of the patients was equal between the ADA (n=283) and IXE (n=283) groups. At 6 months, 269 (95%) patients in the ADA group and 262 (93%) in the IXE one continued to participate in the study. Efficacy analysis was made based on the achievement of the primary endpoint that was considered to be related to the relative number of patients, who had simultaneously achieved improvements in the joints and skin according to the ACR50 and PASI100 criteria.Results and discussion. At 24 weeks, the proportion of patients who had simultaneously achieved ACR50 and PASI100 responses was significantly higher in the IXE group (36%) than in the ADA one (28%) (p=0.036). It was found that the IXE group was not inferior to the ADA one in terms of ACR50 response rates (in 51% (IXE) and 47% (ADA) patients) and was superior in achieving PASI100 response rates (in 60% (IXE) and 47% (ADA) patients) (p=0.001). The IXE group was recorded to have a higher response than the ADA group and in terms of other manifestations of the disease: the severity of skin and nail psoriasis, enthesitis, remission achievement, minimal and very low disease activity, and improved quality of life. Comparable effectiveness was noted for the effect of the drugs on dactylitis, as well as for the simultaneous achievement of remission and low disease activity in psoriatic arthritis according DAPSA. Serious adverse events (SAEs) were recorded in 8.5% (ADA) and 3.5% (IXE) patients.The safety and tolerability of both BAs corresponded to their previously presented safety profile. The findings were also confirmed at 52-week follow-up, presented at the Meetings of the American College of Rheumatology in November 2019 and the European League Against Rheumatism in June 2020, and published in the leading journals of rheumatology.Conclusion. The first randomized placebo-controlled study (SPIRIT H2H) directly comparing the two BAs with different mechanisms of action demonstrated the advantage of IXE over ADA in simultaneously reducing the activity of arthritis and psoriasis and showed their comparable efficacy comparable efficacy regarding joint symptoms. The use of IXE versus ADA was accompanied by the more frequent achievement of a combined endpoint related to the signs of joint and skin damages in patients with PSA, as well as by the quantitatively lower frequency of SAEs in patients with active PSA who had failed previous sDMARD therapy. The findings are of great importance for clinical practice from the point of view of the reasonable choice of a treatment strategy in these patients.