Guselkumab vs Golimumab in PsA TNF Inadequate Responder Patients

Official title

Guselkumab vs Golimumab in PsA TNF Inadequate Responder Patients: a Pragmatic Trial (EVOLUTION)

Overview

The trial is an open-label randomized study that will examine whether switching to a selective IL23 inhibitor (guselkumab) is more effective than switching to a second TNFi (golimumab) among patients with PsA who have an inadequate response to a TNFi.

Detailed description

The primary aim of the trial will be to determine, among psoriatic arthritis (PsA) patients with an inadequate response (IR) to a tumor necrosis factor inhibitor (TNFi), whether switching to a new mechanism of action (MOA), specifically guselkumab (GUS), a selective interleukin 23 inhibitor (IL23i) targeting the p19 subunit, is more effective than switching to another TNFi. The primary hypothesis of this study is that switching to a new MOA may be more effective than switching to a second TNFi. This will be the first trial to test such a switch in PsA patients. Additionally, the proposed study will address the effectiveness of a new therapy, GUS, in a clinical practice setting among patients who are TNF IR.

Interventions

• Drug Guselkumab
  Guselkumab (GUS) subcutaneous injection
• Drug Golimumab
  Golimumab (GOL) subcutaneous injection

Primary outcome measures

• Achievement of cDAPSA low disease activity [Time frame: 12 Months]
• Investigator Global Assessment of Psoriasis of Clear or Almost Clear [Time frame: 12 Months]

Secondary outcome measures (11)

• Minimal Disease Activity (MDA) using PSAID-12 [Time frame: 6 and 12 months]
• Minimal Disease Activity (MDA) using HAQ-DI [Time frame: 6 and 12 months]
• Change in PSAID-12 [Time frame: 6 and 12 months]
• PSAID-12 < 4 [Time frame: 6 and 12 months]
• Change in DLQI [Time frame: 6 and 12 months]
• IGA Among Patients with BSA > 3% at Baseline [Time frame: 6 and 12 months]
• IGA Among Patients with IGA ≥ 2 at Baseline [Time frame: 6 and 12 months]
• Change in Promis Fatigue [Time frame: 6 and 12 Months]
• Resolution of Dactylitis [Time frame: 6 and 12 Months]
• Resolution of Enthesitis [Time frame: 6 and 12 Months]
• Change in BASDAI [Time frame: 6 and 12 Months]

Eligibility criteria

Inclusion criteria

• Psoriatic arthritis meeting CASPAR criteria;
• Active psoriatic arthritis defined by at least 1 swollen joint;
• cDAPSA score ≥ 10; See also Exclusion #4 - cDAPSA must be > 14 in patients without psoriasis.
• Using a TNFi or previously used a single TNFi historically and either never responded or lost response (TNF IR) and planning to switch to a new biologic therapy;
• If using an oral small molecule/csDMARD (i.e., methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, or apremilast), must be on a stable dose for 4 weeks and remain on a stable dose during the study; Use of up to two OSM/csDMARDs is allowed.
• If using NSAIDs, glucocorticoids (<10 mg daily) or topical medications for psoriasis, must be on a stable dose for 4 weeks prior to Screening/Baseline 1 and remain on a stable dose during the study;
• Age 18-80 (patients older than 80 may be more likely to have concomitant osteoarthritis which may make it difficult to assess whether symptoms are related to PsA vs OA).

Exclusion criteria

• Prior exposure to golimumab or another non-TNFi biologic (IL12/23i, JAKi, an IL17i, or an IL23i); prior exposure to a TYK2i is acceptable, but cannot be used during course of the study;
• An adverse event that precludes use of another TNFi (development of drug-induced SLE, allergic reaction, serious infection, heart failure symptoms, demyelination at any point during use of therapy) or any other contraindication or substantial intolerance to a TNFi;
• Use of moderate to high dose glucocorticoids (>10 mg);
• Already meets the primary endpoint at Baseline; \[cDAPSA low disease activity ≤ 14; IGA of psoriasis 0/1\] In patients with psoriasis, cDAPSA can be 10-14 IF the Investigator Global Assessment of Psoriasis ≥ 2.

In patients without psoriasis, cDAPSA must be > 14 to meet eligibility requirements.

• Currently pregnant or actively trying to conceive.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• Family Arthritis Center — Loxahatchee Groves
• Healing Rheumatology — Plant City
• Southwest Florida Rheumatology — Riverview
• Parris and Associates — Lilburn
• University of Massachusetts Chan Medical School — Worcester
• University of Nebraska Medical Center — Omaha
• New York University — New York
• Cincy Arthritis — Blue Ash
• … and 6 more centers

Publications

• Ogdie A, Reddy SM, Gillespie SH, Husni ME, Scher JU, Salomon-Escoto K, Kay J, Luedders BA, Curtis JR, Shields AJS, Chakravarty SD, Gong C, Walsh JA. 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. PMID 40102973

Identifiers

NCT: NCT05669833 · CNTO1959PSA3006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗