Deucravacitinib Improves Patient-Reported Outcomes in Active Psoriatic Arthritis

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The selective, allosteric tyrosine kinase 2 inhibitor demonstrated significant and clinically meaningful improvements in PROs versus placebo in a phase 2 trial of patients with PsA.

Vibeke Strand, MD | Credit: Prime Education

Vibeke Strand, MD

Credit: Prime Education

Deucravacitinib may be a viable tool for improving patient-reported outcomes (PROs) in patients with active psoriatic arthritis (PsA), according to findings from a phase 2, double-blind trial.1

Although the study’s primary endpoint was American College of Rheumatology (ACR) 20 response at week 16, changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical Component Summary (PCS) scores of the Short Form Health Survey-36 (SF-36) as well as other PROs were explored as key secondary endpoints, with results showing deucravacitinib demonstrated significant and clinically meaningful improvements versus placebo.1

“An unmet need exists for safe and efficacious therapies, with novel mechanisms of action that treat the clinical manifestations of disease and improve [health-related quality of life] in patients with active PsA,” lead investigator Vibeke Strand, MD, adjunct clinical professor in the division of immunology and rheumatology at Stanford University School of Medicine, and colleagues wrote.1

Treatment for PsA focuses on controlling inflammation in the affected joints to prevent joint pain and disability, although treatment response varies from patient to patient and efficacy often diminishes over time. Although deucravacitinib, a selective, allosteric tyrosine kinase 2 inhibitor, was well tolerated and more efficacious than placebo in a phase 2 trial of patients with active PsA, its impact on PROs and subsequent health-related quality of life is critical for assessing its true benefit in PsA.1,2

In the phase 2, double-blind trial, investigators randomly assigned patients with active PsA in a 1:1:1 ratio to deucravacitinib 6 mg once daily (QD), 12 mg QD, or placebo for 16 weeks. For inclusion, patients were required to have a PsA diagnosis for ≥6 months, fulfill Classification Criteria for Psoriatic Arthritis (CASPAR) at screening with active joint disease (defined as ≥3 tender and ≥3 swollen joints), 3 mg/Lor higher high-sensitivity C-reactive protein, and ≥1 plaque psoriasis lesion of ≥2 cm. Additionally, eligible patients must have failed or have been intolerant to ≥1 nonsteroidal anti-inflammatory drug, conventional DMARD, and/or tumor necrosis factor inhibitor.1

PROs were assessed using the PsA-specific 12-item Psoriatic Impact of Disease (PsAID-12) as well as the generic PRO instruments HAQ-DI, 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Patient Global Assessment of Disease Activity (PtGA) and Patient Global Assessment of Pain, and SF-36. Using these instruments, investigators assessed changes from baseline at week 16. The percentage of patients reporting improvements with ≥minimum clinically important differences (MCIDs) and the percentages with scores of ≥age- and sex-matched normative values were determined for each PRO.1

In total, 203 patients with PsA were included in this analysis, including 50 (24.6%) with PsA with axial involvement in the opinion of investigators but not confirmed by imaging. Among the cohort, the mean age was 49.8 years and 51.2% of participants were female.1

Investigators noted statistically significant and clinically meaningful improvements were reported for the key secondary endpoints HAQ-DI (adjusted P ≤.002) and SF-36 PCS (adjusted P ≤.006) by patients treated with deucravacitinib 6 mg QD or 12 mg QD versus placebo from baseline to week 16. The adjusted mean difference versus placebo for change from baseline in HAQ-DI at week 16 was −0.26 (95% CI, −0.42 to −0.10; P = .0020) and −0.28 (95% CI, −0.45 to −0.12; P = .0008) for deucravacitinib 6 mg QD and 12 mg QD, respectively. For SF-36 PCS, the adjusted mean difference was 3.3 (95% CI, 0.9 to 5.7; P = .0062) for deucravacitinib 6 mg QD and 3.5 (95% CI, 1.1 to 5.9; P = .0042) for 12 mg QD.1

Clinically meaningful improvements from baseline to week 16 were also observed in SF-36 mental component summary and PsAID-12 scores for deucravacitininb 6 mg QD or 12 mg QD compared with placebo. Improvements were also observed in patients treated with deucravacitinib based on total SF-36 and PsAID-12 scores, as well as specific SF-36 domain and PsAID-12 item scores.1

Investigators pointed out numeric improvements in FACIT-Fatigue, PtGA, and Patient Global Assessment of Pain in both deucravacitinib doses versus placebo, further noting a greater proportion of patients receiving deucravacitinib reported improvements from baseline with ≥MCIDs and PRO scores of ≥normative values versus placebo.1

Investigators also called attention to several notable limitations to these findings, including a lack of adjustment for multiple comparisons beyond HAQ-DI and SF-36 PCS, sample size and study power calculated based on the primary endpoint rather than the secondary PROs, as well as a small sample size and short trial duration limiting the generalizability of these findings to a broader patient population.1

Still, investigators concluded: “The present analysis representing a broad range of PROs important to patients demonstrated that deucravacitinib improved physical and social functioning, mental health, fatigue, and pain in a phase 2 trial in patients with active PsA. These findings were supported by both PsA-specific (PsAID-12) and nonspecific (PtGA, pain, HAQ-DI, and SF-36 PCS and MCS and FACIT-Fatigue) PRO instruments.”

References:

  1. Strand V, Gossec L, Coates LC, et al. Improvements in patient-reported outcomes after treatment with deucravacitinib in patients with psoriatic arthritis: results from a randomized phase 2 trial. Arthritis Care Res (Hoboken). doi:10.1002/acr.25333
  2. Mayo Clinic. Psoriatic arthritis. Diagnosis & Treatment. October 2, 2021. Accessed March 27, 2024. https://www.mayoclinic.org/diseases-conditions/psoriatic-arthritis/diagnosis-treatment/drc-20354081
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