Ixekizumab and Deucravacitinib Show Durable Efficacy in Psoriatic Arthritis

Recent studies highlight durable efficacy of treatments for psoriatic arthritis (PsA), including the IL-17A inhibitor ixekizumab and the TYK2 inhibitor deucravacitinib. In the phase III POETYK PsA-2 trial, deucravacitinib improved outcomes across multiple domains of psoriatic arthritis and had a favourable safety profile. A real-world comparative analysis published in RMD Open showed that patients with PsA receiving ixekizumab demonstrated sustained improvements in joint and skin disease activity over 12 months, with remission rates comparable to or higher than other biologic therapies.

Psoriatic arthritis is a chronic immune-mediated inflammatory condition affecting both the joints and skin, often leading to impaired quality of life and functional limitations. While randomized trials have established the efficacy of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), real-world comparative effectiveness data remain limited. Investigators therefore evaluated treatment response and persistence among patients initiating ixekizumab or other b/tsDMARDs in routine clinical practice.

This prospective observational analysis included 1192 patients with PsA from multiple countries who initiated ixekizumab or other b/tsDMARDs between 2019 and 2022. Baseline characteristics varied across treatment groups. The mean patient age ranged from 50.4 to 53.7 years, 55.9% to 65.3% were women, and average disease duration ranged from 7.3 to 8.9 years. Patients starting ixekizumab tended to have longer disease duration and higher prior exposure to biologic or targeted therapies vs some comparator groups; patients initiating tumor necrosis factor (TNF) inhibitors generally had shorter disease duration and less prior treatment exposure.

At 12 months, patients receiving ixekizumab showed clinically meaningful reductions in joint disease activity, measured by the clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score, along with improvements in skin involvement assessed by body surface area (BSA). Approximately 18.8% of patients who received ixekizumab achieved cDAPSA remission, a percentage that was similar to TNF inhibitor therapy but higher than that observed with pooled IL-12/23 and IL-23 inhibitors. Results of comparative analyses indicated that ixekizumab recipients were about twice as likely to achieve remission or very low disease activity compared with patients receiving those IL-targeting therapies.

Skin outcomes also favored ixekizumab in certain comparisons. Improvements in BSA were greater relative to TNF inhibitor therapy, suggesting more robust control of cutaneous disease in some patients. Patient-reported pain scores also improved to a greater degree vs pooled IL-12/23 and IL-23 inhibitor therapies. However, physician global assessment scores improved more among patients who received TNF or Janus kinase inhibitors, highlighting potential differences between clinician- and patient-perceived outcomes.

Treatment persistence over 12 months was generally similar across biologic classes, with an overall persistence rate near 63.0%. Common reasons for discontinuation included inadequate response, secondary loss of efficacy, and physician decision, while adverse-event discontinuation rates were comparable across groups. Results of subgroup analyses suggested that patients previously exposed to biologic or targeted therapies tended to experience smaller improvements than treatment-naïve patients, though sample sizes for some subgroups were limited. The investigators also noted that improvements seen at earlier time points appeared largely sustained through the 12-month follow-up.

Study limitations include the potential for confounding and selection bias due to the real-world, observational design, limited statistical power from small sample sizes in some treatment groups, and reduced generalizability due to variations in prescribing practices between countries. "Rheumatologists must turn their attention to the patient's broader [health-related quality of life], including the tandem resolution of both joints and skin," the study authors noted.

A separate Italian multicentric retrospective study assessed IXE effectiveness in reducing disease activity in patients with PsA and determined its drug retention rate (DRR) over 24 months. The study included 132 patients (78 females, 54 males; mean age 59.1 ± 11.9 years). At baseline, the median (IQR) Disease Activity in Psoriatic Arthritis (DAPSA) was 16.2 (7.7), and the visual analogue scale (VAS) for pain was 6.5 (3.0). In patients with axial involvement, the median (IQR) Ankylosing Spondylitis Disease Activity Score – C-reactive protein (ASDAS-CRP) was 3.4 (1.3), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 5.0 (1.5).

IXE treatment was associated with statistically significant reductions in DAPSA (p < 0.001), ASDAS-CRP (p < 0.001), BASDAI (p < 0.001), VAS-pain (p < 0.001), Health Assessment Questionnaire (HAQ) (p < 0.001), erythrocyte sedimentation rate (p = 0.014), and CRP (p = 0.004) over 24 months. At 24 months, remission and low disease activity, according to DAPSA thresholds, were achieved by 46.7% and 93.3% of patients, respectively, while Very Low Disease Activity and Minimal Disease Activity criteria were met by 16.0% and 34.0%, respectively. IXE DRR was 82.1%, 76.3%, and 73.3% at 12, 18, and 24 months, respectively, with lower values in female patients (p = 0.036). No differences were observed in IXE DRR when stratifying the cohort by axial involvement (p = 0.84), prior exposure to biologics or tsDMARDs (p = 0.68), or body mass index (BMI) categories (p = 0.48).

In conclusion, IXE enabled rapid and sustained disease control in patients with PsA across multiple disease domains. The high DRR supports its long-term use, regardless of prior biologic exposure or BMI. Gender differences in IXE treatment response may warrant further exploration.