Journal Article

Guselkumab versus golimumab in patients with active psoriatic arthritis and inadequate response to an initial tumor necrosis factor inhibitor: study protocol for EVOLUTION, a pragmatic, phase 3b, open-label, randomized, controlled effectiveness trial

Salomon-Escoto, Karen, Ogdie, Alexis, Curtis, Jeffrey R., Gillespie, Sarah H., Walsh, Jessica A., Luedders, Brent A., Gong, Cinty, Shields, Alisa J. Stephens, Chakravarty, Soumya D., Kay, Jonathan, Husni, M. Elaine, Scher, Jose U., Reddy, Soumya M.

2025

Overview

Background Psoriatic arthritis (PsA) is a multi-domain, inflammatory disease impacting joints, soft tissues, and skin; tumor necrosis factor inhibitors (TNFi) are typically the first biologic following inadequate response (IR) to conventional therapies. Although guidance is lacking on therapy selection after initial TNFi failure, data suggest TNFi-IR PsA patients may benefit from switching to a different mechanism of action (MOA) vs. cycling to another TNFi. Guselkumab is a fully human monoclonal antibody targeting the interleukin-23p19 subunit. Emphasizing practicality and applicability to routine clinical practice, EVOLUTION will pragmatically evaluate whether switching to guselkumab is more effective than cycling to a second TNFi (subcutaneous [SC] golimumab) in TNFi-IR PsA patients. Methods The multicenter, longitudinal, prospective, observational Psoriatic Arthritis Research Consortium study guided eligibility criteria, outcome measures, and sample size estimates. Adults seen in clinical practice with active PsA (≥ 1 swollen joint) while receiving TNFi treatment will be eligible. Participants will be randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, and Q8W; or SC golimumab 50 mg Q4W (no washout period). The novel primary composite endpoint is achievement of clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (≤ 13) and an Investigator’s Global Assessment (IGA) of psoriasis score of 0/1 (scale: 0–4) at Month12. Secondary endpoints include cDAPSA + IGA 0/1 at Month 6; achievement of minimal disease activity, resolution of enthesitis and dactylitis (among patients affected at baseline) at Months 6/12; and mean changes at Months 6/12 in the 12-item PsA Impact of Disease, Dermatology Life Quality Index, Patient-Reported Outcomes Measurements Information System fatigue and depression questionnaires, and Bath Ankylosing Spondylitis Disease Activity Index (patients with physician-determined axial disease). The target sample size is 150 participants (50/treatment group); all analyses are considered exploratory. Discussion EVOLUTION will employ a pragmatic approach, including a novel primary endpoint relevant to clinical practice, to assess whether switching to an alternate MOA biologic with guselkumab is more effective than cycling to a second TNFi among TNFi-IR PsA patients. Trial registration This trial was registered at ClinicalTrials.gov, NCT05669833, on 3 January 2023, https://www.clinicaltrials.gov/study/NCT05669833?term=%20NCT05669833&rank=1 Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized - adverse effects / Antirheumatic Agents - administration & dosage / Antirheumatic Agents - adverse effects / Antirheumatic Agents - therapeutic use / Arthritis, Psoriatic - diagnosis / Arthritis, Psoriatic - drug therapy / Arthritis, Psoriatic - immunology / Biological products / Biomedicine / Cancer / Care and treatment / Clinical medicine / Clinical Trials, Phase III as Topic / Cytokines / Drug dosages / Drug Substitution / Evidence-based medicine / FDA approval / Guselkumab / Health Sciences / Humans / IL-23p19-subunit inhibitor / Interleukins / Longitudinal Studies / Medicine / Medicine & Public Health / Multicenter Studies as Topic / Necrosis / Patients / Pragmatic Clinical Trials as Topic / Prospective Studies / Psoriasis / Psoriatic arthritis / Randomized controlled trial / Skin / Statistics for Life Sciences / Study Protocol / Subcutaneous golimumab / Time Factors / TNFi-IR / Treatment Outcome / Tumor necrosis factor / Tumor Necrosis Factor Inhibitors - adverse effects / Tumor Necrosis Factor Inhibitors - therapeutic use / Tumor Necrosis Factor-alpha - antagonists & inhibitors / Tumor necrosis factor-TNF / Tumors