Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis.

BACKGROUND

Ixekizumab improves signs/symptoms of psoriatic arthritis (PsA). We present an integrated analysis of baseline disease burden and post-baseline outcomes in ixekizumab-treated patients with enthesitis or dactylitis.

METHODS

Data from SPIRIT-P1 and SPIRIT-P2 were integrated. Patients with PsA were randomized to 80-mg ixekizumab every 4 weeks (IXEQ4W) or 2 weeks (IXEQ2W), after a 160-mg starting dose, or to placebo. Inadequate responders at week 16 received rescue therapy. Among patients with baseline enthesitis (Leeds Enthesitis Index [LEI] > 0) or dactylitis (Leeds Dactylitis Index-Basic [LDI-B] > 0), baseline characteristics and disease burden were reported. At week 24, LEI and LDI-B (percentage of patients with resolution [LEI = 0, LDI-B = 0]) were assessed. In pooled treatment groups, the impact of enthesitis or dactylitis resolution on health-related quality of life (HRQoL) (EuroQol-5 Dimensions Visual Analogue Scale [EQ-5D VAS]), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and pain was assessed.

RESULTS

The integrated analysis set comprised 679 patients; of these, 60% (n = 403 of 675) had baseline enthesitis (LEI > 0) and 23% (n = 155 of 676) had baseline dactylitis (LDI > 0). At week 24, ixekizumab-treated patients experienced significantly more resolution than placebo of enthesitis (39% IXEQ4W, 35% IXEQ2W, 21% placebo) and dactylitis (78% IXEQ4W, 65% IXEQ2W, 24% placebo). Furthermore, at entheseal points measured by the LEI, ixekizumab-treated patients had significantly higher resolution of enthesitis compared to placebo. At week 24, among all placebo- and ixekizumab-treated patients, resolution of enthesitis was associated with improvements in function and HRQoL whereas dactylitis resolution was associated with more limited improvements. The least squares mean HAQ-DI improvements from baseline were - 0.44 and - 0.25 for patients who did/did not resolve enthesitis, and - 0.41 and - 0.31 for patients who did/did not resolve dactylitis. EQ-5D VAS improvements were 12.3 and 5.8 for patients who did/did not resolve enthesitis, and 10.8 and 9.8 for patients who did/did not resolve dactylitis.

CONCLUSIONS

Among patients with pre-existing enthesitis or dactylitis, IXEQ2W- and IXEQ4W-treatment resulted in significant improvements in enthesitis and dactylitis. Enthesitis resolution was associated with improvements in patients' function, pain, and HRQoL.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT01695239 , registered on September 25, 2012, and NCT02349295 , registered on October 10, 2014.