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Deucravacitinib selectively binds to a unique pocket in the regulatory domain of TYK2 instead of the highly conserved active site of the catalytic domain,” investigators explained. “This leads to targeted inhibition of immune pathways that are central to psoriasis while limiting off-target effects.”
Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, showed early response and improved clinical efficacy outcomes, including quality of life (QoL), in patients with moderate-to-severe plaque psoriasis, according to a study published in Springer.1
“The mechanism of action of deucravacitinib is distinct from that of other TYK2 or Janus kinase inhibitors in that deucravacitinib selectively binds to a unique pocket in the regulatory domain of TYK2 instead of the highly conserved active site of the catalytic domain, allowing high selectivity of action on TYK2 via allosteric inhibition versus related kinases,” investigators explained. “This leads to targeted inhibition of immune pathways that are central to psoriasis while limiting off-target effects.”
In the post-hoc analysis of a randomized, double-blind, placebo-controlled, Phase 2, 12-week trial (NCT02931838), patients were randomized to receive deucravacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg once daily (QD), or placebo. Efficacy was measured by improvements in body surface area (BSA) involvement, Psoriasis Area and Severity Index (PASI), and static Physician’s Global Assessment (sPGA). QoL was determined by the Dermatology Life Quality Index (DLQI), with the goal of an overall score of 0/1, indicating no effect on the patient’s life.
Eligible patients were diagnosed with moderate-to-severe plaque psoriasis and were able to receive phototherapy or systemic therapy.
A total of 267 patients were enrolled, with 84% (n = 224) completing the 12-week trial. Demographics and disease characteristics at baseline were similar among the treatment groups.
Compared with placebo, deucravacitinib produced greater improvements in all 3 dosage groups as early as Week 1 for PASI and continued through Week 12.
At Week 12, changes in BSA were greater in the deucravacitinib groups (3 mg BID: -18.6, 75.9% decrease; 6 mg BID: -17.2, 69.4% decrease; 12 mg QD: -15.2, 73.7% decrease) when compared with placebo (-7.7). BSA ≤ 1% was achieved in 26.7% of patients in the 3 mg BID group, 37.8% of those in the 6 mg BID group, and 38.6% in the 12 mg QD group, compared with 0% of those receiving the placebo.
QoL showed a similar pattern of efficacy throughout the 12-week period. At Week 4, a greater percentage of patients in the deucravacitinib treatment groups had achieved DLQI 0/1 compared with the placebo group. This continued to increase through Week 12 for those receiving 6 mb BID and 12 mg QD. At the end of Week 12, 55.2% of those receiving deucravacitinib achieved a DLQI 0/1, compared with only 4.4% of those in the placebo cohort.
Patients who had more improvements in their clinical signs and symptoms of skin clearance concurrently had more improvement in QoL. At Week 12, patients who had DLQI 0/1 responses in the deucravacitinib dosage groups also achieved PASI 75 (70.1%), PASI 90 (44.0%), and sPGA (71.6%). Those who attained PASI ≤ 1, PASI 100, BSA ≤ 1%, or BSA ≤ 3% were more likely to have a DLQI score of 0/1.
The rate of achievement of DLQI 0/1 by PASI response was hindered by the limited number of patients in the PASI categories. Additionally, clinical and patient-reported outcomes were not adjusted for statistical significance in the deucravacitinib and placebo groups. Lastly, the sample size was relatively small, and the treatment period was short. However, larger, longer trials are currently ongoing or have been completed.
“This analysis demonstrated that deucravacitinib treatment produced early, clinically meaningful, and similar improvements across several assessments of clinical response (PASI, BSA, sPGA). These improvements were mirrored by QoL improvements, as measured by DLQI,” investigators concluded. “At the three highest dosages tested, a substantial percentage of the deucravacitinib-treated patients met thresholds of clinically meaningful improvement in PASI as well as treat-to-target BSA values recommended by the National Psoriasis Foundation and acceptable response.”
Thaçi D, Strober B, Gordon KB, et al. Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial [published online ahead of print, 2022 Jan 13]. Dermatol Ther (Heidelb). 2022;10.1007/s13555-021-00649-y. doi:10.1007/s13555-021-00649-y