Rapid and sustained improvements in cutaneous and musculoskeletal signs and symptoms with 108 weeks treatment of ixekizumab in psoriatic arthritis in biologic-naive and TNF-inadequate responder patients

Background/Purpose: Ixekizumab (IXE) is a high affinity anti-interleukin (IL)-17A monoclonal antibody approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis (PsA). We evaluated the efficacy of IXE on signs and symptoms of PsA in biologic DMARD (bDMARD)-naïve patients (pts) (SPIRIT-P1; Trial registration number: NCT01695239) or TNF- inadequate responders (TNF-IR) (SPIRIT-P2; NCT02349295). Methods: The SPIRIT-P1 and -P2 study designs were reported previously. Pts with active PsA either bDMARD-naive or with inadequate response or intolerance to prior TNFi-IR were randomized to placebo (PBO), adalimumab (ADA; SPIRIT-P1 only) or 80 mg IXE every 4 (IXE Q4W) or 2 weeks (wks) (IXE Q2W) after a 160-mg starting dose. Efficacy measures included 20% improvement in ACR score and 75/90/100 percent improvement in PASI. Response rates were reported at Wk 108 for pts continuing on IXE treatment (intent-to-treat population). Missing values were imputed by nonresponder imputation for categorical data. Results: After 24 wks of treatment in bDMARD-naive pts (n = 210), ACR 20 response rates were 57.9% (IXE Q4W), 62.1% (IXE Q2W), 57.4% (ADA) versus 30.2% (PBO; P < .001 vs PBO for all comparisons). Among pts who continued on IXE for 108 wks, ACR 20 response rates sustained in 56.1% (IXE Q4W) and 58.3% (IXE Q2W) pts. Similarly, in TNF-IR pts (n = 363), ACR 20 response rates were 53.3% (IXE Q4W), 48.0% (IXE Q2W) vs 19.5% (PBO; P < .001 vs PBO for all comparisons) and these response rates (ACR 20) sustained for 108 wks in 51.6% and 41.5% in IXE Q4W and IXE Q2W arms respectively. In Bio-naïve pts, PASI 100 response rates at Wk 24 were 42.5% (IXE Q4W), 52.5% (IXE Q2W), 23.5% (ADA) versus 3.0% (PBO) and these response rates (PASI 100) sustained for 108 wks in 38.4% (IXE Q4W) and 59.3 % (IXE Q2W). In TNF-IR pts, PASI 100 response rates were 35.3% (IXE Q4W), 27.9% (IXE Q2W), versus 4.5% (PBO) (P < .001 vs PBO for all comparisons) and these response rates sustained for 108 wks in 38.4% (IXE Q4W) and 59.3% (IXE Q2W). In both populations, significant differences in ACR 20 and PASI 75 with IXE versus PBO were observed as early as Week 1. Conclusion: Ixekizumab treatment resulted in significant and rapid improvements in the signs and symptoms of peripheral joint and skin domains of PsA from Week 1 to Week 24, which persisted through 108 weeks in patients who are bDMARD-naïve and TNF-IR.