Deucravacitinib improves ‘broad range’ of patient-reported psoriatic arthritis outcomes
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Key takeaways:
- Deucravacitinib yielded better physical and social functioning vs. placebo.
- The phase 2 study marks “one of the first times” generic domain scores have improved along with disease-specific PsA scores, the researchers said.
Patients with psoriatic arthritis who receive deucravacitinib report significant improvements in mental health, pain, fatigue and other outcomes vs. placebo, according to data published in Arthritis Care & Research.
“This is one of the first times we have seen strong data in both the generic SF-36 domain scores as well as the disease specific Psoriatic Arthritis Impact of Disease (PsAID),” Vibeke Strand, MD, of Stanford University, told Healio.
Deucravacitinib (Sotyktu, Bristol Myers Squibb) is a TYK-2 inhibitor that targets immune-related pathways without blocking metabolic or hematopoietic pathways, like Janus kinase inhibitors do, Strand and colleagues wrote. To evaluate its effect on patient-reported outcomes in PsA, the researchers analyzed data from a previous phase 2 study that found the drug well-tolerated and more effective than placebo.
The current study included 203 patients with active PsA and a mean age of 49.8 years, randomly assigned in an even ratio to receive either deucravacitinib 6 mg, deucravacitinib 12 mg or placebo once daily. During 16 weeks of follow-up, the researchers tracked the percentage of patients achieving minimum clinically important differences in outcome measures, such as the 12-item PsAID, the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Short Form Health Survey physical component summary (SF-36 PCS) and others.
Compared with placebo, greater percentages of patients in both deucravacitinib groups achieved minimum clinically important differences in all patient-reported outcomes at week 16, according to the researchers.
HAQ-DI and SF-36 PCS scores demonstrated significant improvement from baseline in both deucravacitinib cohorts, with greater effects in the higher-dose group. The adjusted mean differences from baseline vs. placebo were –0.26 (95% CI, –0.42 to –0.1) for HAQ-DI in the 6 mg group, –0.28 (95% CI, –0.45 to –0.12) for HAQ-DI in the 12 mg group, 3.3 (95% CI, 0.9–5.7) for SF-36 PCS among the 6 mg group, and 3.5 (95% CI, 1.1–5.9) for SF-36 PCS in those who received 12 mg.
“Deucravacitinib is an exciting, well tolerated product with very strong patient-reported outcomes data despite the limited size of the phase 2 trial,” Strand said. “These are very promising data to be confirmed in phase 3 randomized controlled trials.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
What does TYK2 do? TYK2, encoded by the TYK2 gene, is a non-receptor tyrosine-protein kinase and the first described member of the JAK family, which includes JAK1, JAK2 and JAK3. It catalyzes the activation of signal transducer and activator of transcription (STAT) factors, initiating the expression of cytokines and cellular processes such as division, differentiation and apoptosis.
Through specific receptor binding, cytokines utilize TYK2 to modulate the immune system. Key cytokines like IL-12, IL-23, and Type I IFNs (IFNα and IFNβ) play crucial roles in regulating Th1 cells, Th17 cells and innate immune responses. Additionally, TYK2 facilitates the expression of cytokines IL-6 and IL-10. Although a member of the JAK family, TYK2’s involvement is distinct from metabolic and hematopoietic pathways.
Deucravacitinib is FDA approved for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Deucravacitinib stands apart from JAK 1/2/3 inhibitors by avoiding interference with metabolic or hematopoietic pathways. Its high specificity for TYK2 means it has minimal impact on JAK 1/2/3, resulting in a more favorable risk profile compared to existing JAK inhibitors.
From the small phase 2 trial in PsA, common adverse events (occurring in ≥5% of patients) included nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhea. Notably, there were no serious adverse events, cases of herpes zoster, opportunistic infections or major adverse cardiovascular events associated with deucravacitinib treatment, nor were there significant differences compared with placebo in mean changes in laboratory parameters. Further studies are underway.
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