Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1)

Abstract

Objective: The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients.

Methods: In a phase III study, patients naïve to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156.

Results: Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n = 189) and 38.1 and 8.0 with IXEQ4W (n = 197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response ≥20% (62.5 and 69.8%), ≥50% (56.1 and 51.8%) and ≥70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients.

Conclusion: In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT01695239" title="See in ClinicalTrials.gov">NCT01695239, EudraCT 2011-002326-49.

Keywords: DMARDs (biologic); ixekizumab; psoriasis; psoriatic arthritis; spondyloarthritis.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

ACR and PASI responses The intent-to-treat population was randomized to IXE at week 0 (ixekizumab intent-to-treat population). Starting at week 32, and at all subsequent visits during the extension period, patients were discontinued from study treatment if they failed to demonstrate ≥20% improvement from baseline in both tender and swollen joint counts. IXE Q4W/Q2W: 80 mg ixekizumab every 4 weeks/2 weeks; MI: multiple imputation; mNRI: modified non-responder imputation; NRI: non-responder imputation; PASI: psoriasis area and severity index.

Fig. 2

Enthesitis, dactylitis, HAQ-DI and nail psoriasis The intent-to-treat population was randomized to IXE at week 0 (ixekizumab intent-to-treat population). Starting at week 32, and all subsequent visits during the extension, patients not demonstrating ≥20% improvement from baseline in both tender and swollen joint counts were discontinued. mNRI and MI applied to categorical endpoints and mBOCF and MI applied to continuous endpoints. DI: [HAQ] disability index; IXE Q4W/Q2W: 80 mg ixekizumab every 4 weeks/2 weeks; LDI-B: Leeds dactylitis index-basic; LEI: Leeds enthesitis index; mBOCF: modified baseline observation carried forward; MCID: minimal clinically important differences; MI: multiple imputation; mNRI: modified non-responder imputation; NAPSI: nail area psoriasis severity index; NRI: non-responder imputation.

Fig. 3

Cumulative probability plots for mTSS change from baseline to week 156 Patients are from the long-term extension period population. Missing data were linearly extrapolated if patients had a baseline and ≥1 post-baseline value (i.e. week 52, 108 or 156). At week 52, 0% were imputed, at week 108 1.6% (n = 4) were imputed, and at week 156 10.8% (n = 28) were imputed using linear extrapolation. ADA: adalimumab; IXEQ4W/Q2W: 80 mg ixekizumab every 4 weeks/2 weeks; mTSS: van der Heijde modified total Sharp score; N: total patient number in the long-term extension period population; Nx: number of patients with non-missing change from baseline data after linear extrapolation; PBO: placebo.