Responses to Ixekizumab in Male and Female Patients with Psoriatic Arthritis: Results from Two Randomized, Phase 3 Clinical Trials

Abstract

Introduction: Differences in psoriatic arthritis (PsA) treatment response between sexes for ixekizumab, an interleukin-17A antagonist, are largely unexplored. This analysis used data from randomized clinical trials (RCTs) evaluating ixekizumab to study differences in treatment response between male and female patients with PsA.

Methods: We used pooled data from patients enrolled in SPIRIT-P1 and SPIRIT-P2 (NCT01695239 and NCT02349295, respectively), phase 3 RCTs evaluating ixekizumab every 4 and 2 weeks in patients with active PsA. Subgroups of patients were defined by sex (male, female). Efficacy was measured by the proportion of male and female patients achieving American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70), minimal disease activity or very low disease activity (MDA/VLDA), and Disease Activity Index for Psoriatic Arthritis (DAPSA) scores representing low disease activity (LDA) or remission through week 156. Changes from baseline in components of the above measures were also assessed through week 156.

Results: Compared to male patients at baseline, female patients were older, had higher body mass index and lower C-reactive protein levels, and had worse tender joint count, Health Assessment Questionnaire Disability Index, and Leeds Enthesitis Index scores. Through week 156, female patients in all treatment arms had lower response rates than male patients in all analyzed composite measures (ACR20/50/70; MDA/VLDA; DAPSA LDA/remission), with significant differences observed at multiple timepoints in both ixekizumab treatment arms. Female patients also had smaller numeric changes from baseline in the composite measures' individual components.

Conclusion: Compared to female patients, male patients had greater response rates in ACR20/50/70, MDA/VLDA, and DAPSA LDA/remission and numerically larger improvements in these measures' individual components, although clinical significance is unclear. Continued efforts to understand sex differences in treatment response may provide insights that can help optimize clinical decision making.

Trial registration: ClinicalTrials.gov identifiers, NCT01695239 and NCT02349295.

Keywords: Ixekizumab; Outcome measures; Psoriatic arthritis; Sex differences; Women’s health.

© 2022. The Author(s).

Figures

Fig. 1

Percentage of male and female patients treated with ixekizumab Q4W achieving ACR20/50/70 (a, b), MDA/VLDA (c, d), and DAPSA LDA/DAPSA Remission (e, f) through 156 weeks. Missing data were imputed by mNRI. P values were calculated for proportions of male vs. female responders; *P < 0.05, ‡P < 0.01, †P < 0.001. ACR20/50/70 20%, 50%, or 70% improvement from baseline in the American College of Rheumatology criteria; DAPSA Disease Activity Index for Psoriatic Arthritis, LDA low disease activity, MDA minimal disease activity, Ns number of patients in the subgroup, VLDA very low disease activity, Q4W every 4 weeks

Fig. 2

Percentage of male and female patients treated with ixekizumab Q2W achieving ACR20/50/70 (a, b), MDA/VLDA (c, d), and DAPSA LDA/DAPSA Remission (e, f) through 156 weeks. Missing data were imputed by mNRI. P values were calculated for proportions of male vs. female responders; *P < 0.05, ‡P < 0.01, †P < 0.001. DAPSA Disease Activity Index for Psoriatic Arthritis, LDA low disease activity, MDA minimal disease activity, Ns number of patients in the subgroup, VLDA very low disease activity, Q2W every 2 weeks

Fig. 3

Changes from baseline in male and female patients treated with ixekizumab Q4W for TJC (a), SJC (b), Pain VAS (c), PtGA (d), PhGA (e), HAQ-DI (f), CRP (g), PASI (h), and LEI (i) through 156 weeks. Missing data were imputed by mBOCF. TJC includes 68 joints; SJC includes 66 joints. Pain VAS, PtGA, and PhGA are measured on a 0–100 scale. HAQ-DI is measured on a 0–3 scale. CRP is measured in mg/L. PASI is measured on a 0–72 scale. LEI is measured on a 0–6 scale. Change from baseline in PASI was measured in 77 male patients and 64 female patients with ≥ 3% body surface area affected at baseline. Change from baseline in LEI was measured in 57 male patients and 79 female patients with LEI > 0 at baseline. CRP C-reactive protein, HAQ-DI Health Assessment Questionnaire Disability Index, LEI Leeds Enthesitis Index, mBOCF modified baseline observation carried forward, Ns number of patients in subgroup, Pain VAS Pain Visual Analog Scale, PASI Psoriasis Area and Severity Index, PhGA Physician’s Global Assessment of Disease Activity, PtGA Patient’s Global Assessment of Disease Activity, SJC swollen joint count, TJC tender joint count, Q4W every 4 weeks

Fig. 4

Changes from baseline in male and female patients treated with ixekizumab Q2W for TJC (a), SJC (b), Pain VAS (c), PtGA (d), PhGA (e), HAQ-DI (f), CRP (g), PASI (h), and LEI (i) through 156 weeks. Missing data were imputed by mBOCF. TJC includes 68 joints; SJC includes 66 joints. Pain VAS, PtGA, and PhGA are measured on a 0–100 scale. HAQ-DI is measured on a 0–3 scale. CRP is measured in milligrams per liter (mg/L). PASI is measured on a 0–72 scale. LEI is measured on a 0–6 scale. Change from baseline in PASI was measured in 67 male patients and 60 female patients with ≥ 3% body surface area affected at baseline. Change from baseline in LEI was measured in 50 male patients and 91 female patients with LEI > 0 at baseline. CRP C-reactive protein, HAQ-DI Health Assessment Questionnaire Disability Index, LEI Leeds Enthesitis Index, mBOCF modified baseline observation carried forward, Ns number of patients in subgroup, Pain VAS Pain Visual Analog Scale, PASI Psoriasis Area and Severity Index, PhGA Physician’s Global Assessment of Disease Activity, PsA psoriatic arthritis, PtGA Patient’s Global Assessment of Disease Activity, SJC swollen joint count, TJC tender joint count, Q2W every 2 weeks