Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study

Abstract

Objectives: Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics.

Method: This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders.

Results: 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100.

Conclusion: Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

Keywords: Disease control; Domain; Guselkumab; Patient-reported outcome; Psoriatic arthritis.

Fig. 1

Proportions of guselkumab-randomized patients achieving ACR50 and ACR70 response through Week 100 by baseline characteristics. Proportions displayed for subgroups indicate the response rates (utilizing NRI) at Week 100. ACR50: ≥ 50% improvement in American College of Rheumatology response criteria; ACR70: ≥ 70% improvement in American College of Rheumatology response criteria; BMI: body mass index; BSA: body surface area; CRP: C-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; GUS: guselkumab; MTX: methotrexate; NRI: nonresponder imputation; PASI: Psoriasis Area and Severity Index; PsA: psoriatic arthritis; Q4W: every 4 weeks; Q8W: every 8 weeks; W: Week

Fig. 2

Proportions of guselkumab-randomized patients achieving PASI 100 and IGA 0 through Week 100 by baseline characteristics. Achievement of PASI 100 and IGA 0 was assessed among patients with BSA ≥ 3% and IGA ≥ 2 at baseline. Proportions displayed for subgroups indicate the response rates (utilizing NRI) at Week 100. BMI: body mass index; BSA: body surface area; CRP: C-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; GUS: guselkumab; IGA: Investigator’s Global Assessment; MTX: methotrexate; NRI: nonresponder imputation; PASI: Psoriasis Area and Severity Index; PASI 100: 100% improvement in PASI; PsA: psoriatic arthritis; Q4W: every 4 weeks; Q8W: every 8 weeks; W: Week

Fig. 3

Proportion of guselkumab-randomized patients achieving resolution of dactylitis and enthesitis through Week 100 by baseline characteristics. Resolution of dactylitis and enthesitis was assessed among patients with dactylitis and enthesitis at baseline, respectively. Proportions displayed for subgroups indicate the response rates (utilizing NRI) at Week 100. BMI: body mass index; BSA: body surface area; CRP: C-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; GUS: guselkumab; MTX: methotrexate; NRI: nonresponder imputation; PASI: Psoriasis Area and Severity Index; PsA: psoriatic arthritis; Q4W: every 4 weeks; Q8W: every 8 weeks; W: Week

Fig. 4

Proportion of guselkumab-randomized patients achieving HAQ-DI and FACIT-Fatigue response through Week 100 by baseline characteristics. Achievement of HAQ-DI response (improvement ≥ 0.35) FACIT-Fatigue response (improvement ≥ 4) was assessed among patients with baseline HAQ-DI ≥ 0.35 and baseline FACIT-Fatigue ≤ 48, respectively. Proportions displayed for subgroups indicate the response rates (utilizing NRI) at Week 100. BMI: body mass index; BSA: body surface area; CRP: C-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; FACIT: Functional Assessment of Chronic Illness Therapy; GUS: guselkumab; HAQ-DI: Health Assessment Questionnaire-Disability Index; MTX: methotrexate; NRI: nonresponder imputation; PASI: Psoriasis Area and Severity Index; PsA: psoriatic arthritis; Q4W: every 4 weeks; Q8W: every 8 weeks; W: Week

Fig. 5

Proportion of guselkumab-randomized patients achieving PASDAS LDA and MDA through Week 100 by baseline characteristics. Proportions displayed for subgroups indicate the response rates (utilizing NRI) at Week 100. BMI: body mass index; BSA: body surface area; CRP: C-reactive protein; csDMARD: conventional synthetic disease-modifying antirheumatic drug; GUS: guselkumab; LDA: low disease activity; MDA: minimal disease activity; MTX: methotrexate; NRI: nonresponder imputation; PASDAS: Psoriatic Arthritis Disease Activity Score; PASI: Psoriasis Area and Severity Index; PsA: psoriatic arthritis; Q4W: every 4 weeks; Q8W: every 8 weeks; W: Week