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. 2024 Dec;11(6):1501-1517.
doi: 10.1007/s40744-024-00702-0. Epub 2024 Sep 11.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials

Jeffrey R Curtis  1 , Atul Deodhar  2 , Enrique R Soriano  3 , Emmanouil Rampakakis  4   5 , May Shawi  6 , Natalie J Shiff  7   8 , Chenglong Han  9 , William Tillett  10 , Dafna D Gladman  11
Affiliations

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials

Jeffrey R Curtis et al. Rheumatol Ther. 2024 Dec.

Abstract

Introduction: Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA).

Methods: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients.

Results: Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4).

Conclusions: In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52.

Trial registration: DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Keywords: Disease activity; Fatigue; Guselkumab; Joint disease; Minimal clinically meaningful improvement; Pain; Patient-reported outcome; Physical function; Psoriatic arthritis; Skin psoriasis.

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Conflict of interest statement

Declarations Conflict of interest Jeffrey R Curtis: received grant/research support from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, UCB, and NIAMS P30AR072583; consulting fees from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB. Atul Deodhar: received consulting fees for participation in advisory boards from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; research grant funding from AbbVie, Eli Lilly, Novartis, Pfizer, and UCB; speaker fees from Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Enrique R Soriano: speakers bureau for AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB; consulting fees from AbbVie, Janssen, Novartis, and Roche; grant/research support from AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB. Emmanouil Rampakakis: consulting fees from Janssen; employee of JSS Medical Research. May Shawi: shareholder of Johnson & Johnson; employee of Janssen Research & Development, LLC. Natalie J Shiff: shareholder of AbbVie, Gilead, Iovance, Jazz Pharmaceuticals, Johnson & Johnson, Novavax, and Viatris; employee of Janssen Scientific Affairs, LLC, a Johnson & Johnson company, at the time this work was performed (current employee of Alpine Immune Sciences, a Vertex company). Chenglong Han: shareholder of Johnson & Johnson; employee of Janssen Global Services, LLC. William Tillett: received consulting fees from AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Ono-Pharma, Pfizer, and UCB; grant/research support from AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, and UCB; speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB. Dafna D Gladman: grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB; consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Ethical Approval The DISCOVER-1 (NCT03162796) and DISCOVER-2 (NCT03158285) studies were conducted in accordance with the principles of the Declaration of Helsinki and International Council for Harmonization Guidelines for Good Clinical Practice. Each participating site's governing ethical body approved study protocols, and all patients provided written informed consent.

Figures

Fig. 1
Fig. 1
Time to achieve MCII in joints (A, B), skin (C), pain (D), and overall disease activity (E, F) through week 24 among patients receiving guselkumab Q4W and Q8W vs. placebo. cDAPSA, Clinical Disease Activity Index for Psoriatic Arthritis, CI confidence interval, HR hazard ratio, MCII minimal clinically important improvement, PASDAS Psoriatic Arthritis Disease Activity Score, PBO placebo, PtGA patient global assessment, Q4W every 4 weeks, Q8W every 8 weeks. Time to MCII among patients receiving guselkumab Q4W or Q8W compared with placebo was assessed using Cox regression, adjusting for baseline levels of the respective outcome, prior tumor necrosis factor inhibitor use, and baseline use of conventional synthetic disease-modifying antirheumatic drugs
Fig. 2
Fig. 2
Associations between early MCII achievement, at first timepoint assessed, in joints (A, B), skin (C), pain (D), and overall disease activity (E, F) and stringent response (ACR50, ACR70, cDAPSA LDA, PASDAS LDA, and MDA) at week 24 among guselkumab-randomized patients (combined Q4W and Q8W). ACR50/70 ≥ 50%/70% improvement in American College of Rheumatology response criteria, cDAPSA clinical Disease Activity Index for Psoriatic Arthritis, CI confidence interval, csDMARD conventional synthetic disease-modifying antirheumatic drug, LDA low disease activity, MCII minimal clinically important improvement, MDA minimal disease activity, OR odds ratio, PASDAS Psoriatic Arthritis Disease Activity Score, PtGA patient global assessment, Q4W every 4 weeks, Q8W every 8 weeks, TNFi tumor necrosis factor inhibitor, W week. Response rates for achieving MCII at week 24 were determined for W4/W8 responders and nonresponders using nonresponder imputation and compared using logistic regression, adjusting for prior TNFi use and baseline csDMARD use
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