Baseline Characteristics and Treatment Response to Ixekizumab Categorised by Sex in Radiographic and Non-radiographic Axial Spondylarthritis Through 52 Weeks: Data from Three Phase III Randomised Controlled Trials

Abstract

Objectives Assess baseline characteristics and treatment response to ixekizumab (IXE) categorised by sex in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA) up to 52 weeks. Methods Data were analysed from three randomised controlled trials of IXE through 52 weeks. Patients fulfilled ASAS classification criteria for r-axSpA or nr-axSpA and were randomised to receive 80 mg subcutaneous administration of IXE every 2 weeks (Q2W) or 4 weeks (Q4W), or placebo (16 weeks COAST-V/W; 52 weeks COAST-X). Baseline characteristics and treatment outcomes were assessed. Patients were categorised by sex; methods included non-responder imputation for categorical variables, and modified baseline observation carried forward for continuous efficacy variables. Results At presentation, female patients had higher disease burden as reflected by significantly higher spinal pain at night, fatigue scores and pain/swelling in joints other than the neck, back or hip. ASAS40 response rate with the approved label dose, IXEQ4W, was achieved in 39% of male patients with r-axSpA by week 16, and 44% by week 52. For female patients, 16.7% and 33.3% achieved ASAS40 at week 16 and 52, respectively. In nr-axSpA, 46% of male patients achieved ASAS40 at week 16 and 30% at week 52. In total, 23.9% of female patients achieved ASAS40 at week 16, and 30.4% at week 52. Conclusions This analysis demonstrates that for the axSpA disease spectrum, female patients present with higher disease burden. Following treatment with IXE, there is a higher proportion of male responders up to 16 weeks, while female patients show less robust responses for the first 16 weeks but larger responses from weeks 16 through 52. Trial Registration Numbers NCT02696785, NCT02696798 and NCT02757352. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02132-2.

Sexual dimorphism in the prevalence, manifestation and outcomes of axial spondyloarthritis

“…Interestingly, male and female patients with axSpA tend to differ in their responses to treatment. In this Review, we discuss sex and gender differences and how they might con tribute to differences in phenotypes and therapeutic responses in axSpA [13][14][15][16][17][18][19] .…”

Sex differences in musculoskeletal injury and disease risks across the lifespan: Are there unique subsets of females at higher risk than males for these conditions at distinct stages of the life cycle?

“…Long considered mainly a disease of men, particularly ankylosing spondylitis, has more recently been reported to also affect a subset of females ( Masi, 1992 ; Wright et al, 2020 ; Cunha et al, 2022 ; Marzo-Ortega et al, 2022 ; Stovall et al, 2022 ). Sex differences in disease presentation characteristics ( Chimenti et al, 2021 ), as well as disease activity compared to males have been reported, with females exhibiting higher disease activity than males and exhibiting different response patterns to clinical interventions ( Mease et al, 2021 ; Stovall et al, 2022 ; van der Horst-Bruinsma et al, 2022 ).…”

Axial spondyloarthritis: one year in review 2023

“…Taking into account how the gender differences might have an impact on SpA outcomes, van der Horst-Bruinsma and colleagues observed that male patients had a better and more rapid response to IXE than women, who experienced worse outcomes, especially those with a diagnosis of nr-axSpA (75).…”

“…• In axSpA patients treated with ixekizumab, a withdrawal of the drug, the presence of anti-drug antibodies, an abnormal BMI and higher values of C-reactive protein or ASDAS were shown to be risk factors for disease flares. Moreover, female sex and a diagnosis of nr-axSpA seem to be associated with reduced efficacy of the drug (74,75). • Brodalumab was effective and safe in Asian patients with both r-and nr-axSpA (76).…”