Ixekizumab makes very low disease activity and remission with psoriatic arthritis disease activity score possible in active psoriatic arthritis patients for up to 1 year: Spirit-P1 and Spirit-P2 trials

Background: Treatment goals in psoriatic arthritis (PsA) are moving toward attainment of absolute therapeutic thresholds rather than relative improvement. Minimal disease activity (MDA) and very low disease activity (VLDA); Disease Activity in Psoriatic Arthritis (DAPSA) LDA and DAPSA Remission; and Psoriatic Arthritis Disease Activity Score (PASDAS) LDA and PASDAS VLDA are validated composite indices used to measure disease activity states in PsA. Objectives: The effect of ixekizumab (IXE), as assessed by composite endpoints that incorporate multiple disease domains, was explored up to 52 weeks for the SPIRIT-P11 and SPIRIT-P22 trials. Methods: Data were analysed from 2 double-blind, phase III SPIRIT trials investigating the efficacy and safety of IXE, a high-affinity monoclonal antibody selectively targeting interleukin-17A, for patients with active PsA. For SPIRIT-1 (NCT01695239), patients who were biologic disease-modifying antirheumatic drug (DMARD)-naive were randomised to placebo (n=106) or 80 mg IXE every 4 weeks (Q4W, n=107) or every 2 weeks (Q2W, n=103) after a 160 mg starting dose. For SPIRIT-2 (NCT02349295), patients who had an inadequate response or were intolerant to tumour necrosis factor inhibitors (TNFi) were randomised to placebo (n=118) or 80 mg IXE every 4 weeks (Q4W, n=122) or every 2 weeks (Q2W, n=123) after a 160 mg starting dose. MDA, MDA VLDA, DAPSA LDA, DAPSA Remission, PASDAS LDA, and PASDAS VLDA composite endpoints were evaluated. Imputation for categorical responses was non-responder imputation. Treatment comparisons (with respect to placebo up to Week 24) based on the intent-to-treat population were made using a logistic regression model. Data up to Week 52 are summarised descriptively. Results: The therapeutic threshold results are summarised in table 1. At Week 24, the percentage of patients achieving MDA, MDA VLDA, DAPSA LDA, DAPSA Remission, PASDAS LDA, and PASDAS VLDA was greater with IXE Q4W and IXE Q2W compared with placebo. In patients who continued treatment with IXE through Week 52, response rates of these therapeutic thresholds were either sustained or further improved. Conclusions: Regardless of previous TNFi exposure, in patients with active PsA, a higher proportion of IXE-treated compared with placebo-treated patients achieved MDA and MDA VLDA, DAPSA LDA and DAPSA Remission, and PASDAS LDA and PASDAS VLDA at Week 24. At Week 52, the extent of IXE clinical response was sustained or further improved.