Ixekizumab makes therapeutic thresholds possible in active psoriatic arthritis patients: results from spirit trials

Introduction: Treatment goals in psoriatic arthritis (PsA) are moving toward attainment of absolute therapeutic thresholds rather than relative improvement. Objective:To explore the effect of ixekizumab (IXE), an anti‐IL‐17A monoclonal antibody, as assessed by composite endpoints, up to 52 weeks (wks) for the SPIRIT‐P1 and SPIRIT‐P2 trials. Methods: Data were analyzed from 2 double‐blind, phase 3 trials investigating the effcacy and safety of IXE in active PsApatients (pts). For SPIRIT‐1 [1] biologic disease‐modifying antirheumatic drug‐naïve pts were randomized to placebo (PBO, n = 106) or 80 mg IXE every 4 wks (Q4W, n = 107) or every 2 wks (Q2W, n = 103) post 160 mg starting dose. For SPIRIT‐2 [2] (inadequate responders to tumor necrosis factor inhibitors [TNFi]) pts were randomized to PBO (n = 118) or 80 mg IXE Q4W (n = 122) or Q2W (n = 123) post 160 mg starting dose. Minimal disease activity (MDA), MDA very low disease activity (VLDA), Disease Activity in Psoriatic Arthritis (DAPSA) LDA, DAPSA remission, Psoriatic Arthritis Disease Activity Score (PASDAS) LDA, and PASDAS VLDA composite endpoints were evaluated. Imputation for categorical responses was non‐responder imputation. Treatment comparisons (with placebo up to Wk 24) based on the intent‐to‐treat population were made using a logistic regression model. Data up to Wk52 are summarized. Results: At Wk 24, percentage of pts achieving MDA (SPIRIT‐P1 Q4W: 29.9; Q2W: 40.8;

PBO:

15.1; SPIRIT‐P2 Q4W: 27.9; Q2W: 31.9;

PBO:

3.4), MDA VLDA (SPIRIT‐P1 Q4W: 10.3; Q2W: 11.7;

PBO:

0.9; SPIRIT‐P2 Q4W: 12.3; IXEQ2W: 3.3;

PBO:

0.8), DAPSA LDA (SPIRIT‐P1 Q4W: 31.8; Q2W: 34.0;

PBO:

17.9; SPIRIT‐P2 Q4W: 25.4; Q2W: 27.6;

PBO:

11.1), DAPSA remission (SPIRIT‐P1 Q4W: 15.9; Q2W: 24.3;

PBO:

4.7; SPIRIT‐P2 Q4W: 14.8; Q2W: 7.3;

PBO:

0.8), PASDAS LDA (SPIRIT‐P1 Q4W: 42.1; Q2W: 50.5;

PBO:

18.9; SPIRIT‐P2 Q4W: 39.3; Q2W: 35.0;

PBO:

6.8), and PASDAS VLDA (SPIRIT‐P1 Q4W: 11.2; Q2W: 20.4;

PBO:

1.9; SPIRIT‐P2 Q4W: 13.1; Q2W: 7.3;

PBO:

0.0) was greater with Q4W and Q2W versus placebo. Similarly, at Wk 52 the response rates were either sustained or improved: MDA (SPIRIT‐P1 Q4W: 39.3; Q2W: 36.9; SPIRIT‐P2 Q4W: 34.4; Q2W: 23.6), MDA VLDA (SPIRIT‐P1 Q4W: 14.0; Q2W: 15.5; SPIRIT‐P2 Q4W: 12.3; Q2W: 6.5), DAPSA LDA (SPIRIT‐P1 Q4W: 30.8; Q2W: 29.1; SPIRIT‐P2 Q4W: 34.4; Q2W: 26.0), DAPSA remission (SPIRIT‐P1 Q4W: 22.4; Q2W: 29.1; SPIRIT‐P2 Q4W: 18.9; Q2W: 11.4), PASDAS LDA (SPIRIT‐P1 Q4W: 43.0; Q2W: 50.5; SPIRIT‐P2 Q4W: 45.1; Q2W: 30.9), and PASDAS VLDA (SPIRIT‐P1 Q4W: 17.8; Q2W: 26.2; SPIRIT‐P2 Q4W: 17.2; Q2W: 11.4). Conclusions: Regardless of previous TNFi exposure, a higher proportion of IXE‐treated pts achieved MDA and MDA VLDA, DAPSA LDA and DAPSA remission, and PASDAS LDA and PASDAS VLDA at Wk 24 versus placebo. At Wk 52, the extent of IXE clinical response sustained or further improved.