Deucravacitinib, a selective, TYK2 inhibitor, in psoriatic arthritis: achievement of minimal disease activity components in a phase 2 trial

Abstract

Objectives: Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor belonging to a distinct class of enzyme inhibitors. In a phase 2 trial in psoriatic arthritis (NCT03881059), deucravacitinib was significantly more efficacious than placebo across multiple endpoints, including achieving minimal disease activity (MDA). This post hoc analysis further evaluated the achievement of individual components of the MDA criteria with deucravacitinib treatment and the time course of responses in the phase 2 trial.

Methods: Patients (N = 203) were randomized 1:1:1 to once daily treatment with placebo, deucravacitinib 6 mg or deucravacitinib 12 mg. The proportions of patients achieving MDA and each of the seven individual MDA components through week 16 were assessed.

Results: At baseline, although some patients met criteria for individual MDA components, none of the patients met the composite MDA criterion, and all components were balanced overall across treatment arms. Treatment with deucravacitinib was associated with a numerically greater mean reduction from baseline in all MDA components vs placebo over 16 weeks of treatment. At week 16, a greater percentage of patients treated with either dose of deucravacitinib vs placebo achieved the threshold criteria for meeting MDA in each of the components.

Conclusions: More patients treated with deucravacitinib met each of the MDA components vs placebo, along with a higher rate of MDA response, after 16 weeks of treatment.

Keywords: TYK2; deucravacitinib; phase II; psoriatic arthritis; tyrosine kinase 2 inhibitor.

Graphical abstract

Figure 1.

Proportions of patients meeting individual MDA component criteria at (A) baseline and (B) week 16. Components are ordered graphically from least frequently achieved (left) to most frequently achieved (right). *P < 0.05, **P < 0.01, ***P < 0.001. P-values vs placebo. Nonresponder imputation was used to impute missing data. Enthesitis was assessed using Leeds Enthesitis Index. ^aPatients with BSA <3% at baseline did not have postbaseline PASI or BSA skin assessments per protocol and are presented in the hashed shading in (A); (B) data for this component reflect only patients with BSA ≥3% at baseline (placebo, n = 54; deucravacitinib 6 mg, n = 59; deucravacitinib 12 mg, n = 52). BSA: body surface area; HAQ-DI: HAQ–Disability Index; MDA: minimal disease activity; PASI: Psoriasis Area Severity Index; Pain: Patient Global Assessment of Pain; PtGA: Patient Global Assessment of Disease Activity; QD: once daily; SJC: swollen joint count; TJC: tender joint count; VAS: visual analogue scale; w/o: without; wk: week

Figure 2.

Proportions of patients achieving MDA through week 16. *P < 0.05 and **P < 0.01. P-values vs placebo. Nonresponder imputation was used to impute missing data. MDA: minimal disease activity; QD: once daily

Figure 3.

Mean change from baseline through week 16 in individual MDA components. ^aAnalyses were done post hoc using data as observed. ^bPatients with BSA involvement ≥3% at baseline. ^cModified baseline observation carried forward was used to handle missing data. ^dMeasured using the Leeds Enthesitis Index in patients with a score ≥1 at baseline. BSA: body surface area; HAQ-DI: HAQ–Disability Index; MDA: minimal disease activity; PASI: Psoriasis Area and Severity Index; QD: once daily

Figure 4.

Achievement of MDA components at week 16 in MDA responders and MDA nonresponders. Response rate of each individual MDA component at week 16 in all patients is shown, split by those who were overall MDA responders (solid shading) and overall MDA nonresponders (hatched shading) at week 16. Response rate is calculated as n/N and shown within or above the respective bars. Interpretation of data is limited by small sample size. Nonresponder imputation was used to impute missing data. Enthesitis assessed using Leeds Enthesitis Index. BSA: body surface area; HAQ-DI: HAQ–Disability Index; MDA: minimal disease activity; Pain: Patient Global Assessment of Pain; PASI: Psoriasis Area Severity Index; PtGA: Patient Global Assessment of Disease Activity; QD: once daily; SJC: swollen joint count; TEP: tender entheseal point; TJC: tender joint count; VAS: visual analogue scale