Guselkumab vs Golimumab in PsA TNF Inadequate Responder Patients (EVOLUTION)
Study Details
Study Description
Brief Summary
The trial is a double-blinded randomized study with three arms: Golimumab (GOL) 50 mg subcutaneous injection every 4 weeks, guselkumab (GUS) 100 mg subcutaneous injection every 8 weeks, and GUS 100 mg every 4 weeks. It 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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), is more effective than switching to another TNFi. The proposed trial will test two important management questions. The recommended first biologic therapy for PsA is typically a TNFi, concordant with the ACR/NPF treatment guidelines, but it remains unknown whether, after inadequate response to a first TNFi (TNF IR), switching to a new MOA or a second TNFi is more effective in PsA.5, 9 We hypothesize that switching to a new MOA is more effective than switching to a second TNFi. This will be the first trial to test such a switch in PsA. Additionally, the proposed study will address the effectiveness of a new therapy, GUS, in the clinical practice setting among patients who are TNF IR. GUS was approved by the FDA in July 2020 for active PsA and, as with other new to market therapies, is currently used primarily in patients who have failed prior biologics. However, the two pivotal RCTs enrolled mostly biologic naïve patients.10, 11 Furthermore, in a European study, patients who had failed a TNFi had a lower response to GUS q8 weeks than those who were TNF naïve. We hypothesize that patients who are TNF IR may need more frequent dosing of the drug.
The proposed randomized trial will employ a trial design that is novel to PsA in three ways:
- We will use a composite measure as the primary outcome that was specifically designed for PsA (supported by evidence from our preliminary data); 2) We will apply a pragmatic approach to assessing therapy effectiveness by recruiting a patient population that is representative of patients seen in clinical practice and enrolling patients at the time of the switch rather than requiring a washout (as drugs are prescribed in clinical practice); 3) We will utilize remote monitoring of intermediate outcomes, reducing the number of visits over the course of one year. The proposed trial addresses important knowledge gaps in the management of PsA, trial designs in PsA, and builds on a longitudinal cohort study to define outcome measures for this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: GOL (4 Weeks) Golimumab (GOL) 50 mg subcutaneous injection every 4 weeks |
Drug: Golimumab
Three interventions will be tested: Golimumab (GOL) 50 mg subcutaneous injection every 4 weeks (a TNFi at the approved dose for active PsA), guselkumab (GUS) 100 mg subcutaneous injection every 8 weeks (dose approved for moderate-to-severe plaque psoriasis and active PsA; a placebo injection will be given on the 'off' month), and GUS 100 mg every 4 weeks (dose tested in DISCOVER 1 and 2 but not currently FDA approved).
Other Names:
|
| Active Comparator: GUS (8 Weeks) Guselkumab (GUS) 100 mg subcutaneous injection every 8 weeks |
Drug: Guselkumab
Three interventions will be tested: Golimumab (GOL) 50 mg subcutaneous injection every 4 weeks (a TNFi at the approved dose for active PsA), guselkumab (GUS) 100 mg subcutaneous injection every 8 weeks (dose approved for moderate-to-severe plaque psoriasis and active PsA; a placebo injection will be given on the 'off' month), and GUS 100 mg every 4 weeks (dose tested in DISCOVER 1 and 2 but not currently FDA approved).
Other Names:
|
| Experimental: GUS (4 Weeks) GUS 100 mg every 4 weeks |
Drug: Guselkumab
Three interventions will be tested: Golimumab (GOL) 50 mg subcutaneous injection every 4 weeks (a TNFi at the approved dose for active PsA), guselkumab (GUS) 100 mg subcutaneous injection every 8 weeks (dose approved for moderate-to-severe plaque psoriasis and active PsA; a placebo injection will be given on the 'off' month), and GUS 100 mg every 4 weeks (dose tested in DISCOVER 1 and 2 but not currently FDA approved).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- cDAPSA [12 Months]
Disease Activity in Psoriatic Arthritis: a combination score of tender joint count, swollen joint count, patient assessment of pain, and patient global assessment of disease activity.
- IGA Psoriasis [12 Months]
Investigator global assessment (IGA) of psoriasis
Secondary Outcome Measures
- PSAID-12 [6 and 12 months]
Psoriatic Arthritis Impact of Disease Questionnaire
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Psoriatic arthritis meeting CASPAR criteria;
-
Active psoriatic arthritis defined by the presence of at least 2 swollen joints OR 1 swollen joint and 1 site of active enthesitis OR active dactylitis involving 2 joints (this captures the majority of patients switching therapy in our cohort);
-
At least one active psoriasis plaque;
-
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 a single oral small molecule/csDMARD (i.e., methotrexate, leflunomide, hydroxycloroquine, sulfasalazine, or apremilast), must be on a stable dose for 4 weeks and remain on a stable dose during the study; Only use of a single OSM/csDMARD is allowed.
-
If using NSAIDs, glucocorticoids (<10 mg daily) or topical medications for psoriasis, must be on a stable dose for 4 weeks 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);
-
An adverse event the 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 meet the primary outcome at screening or baseline
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
- Janssen Scientific Affairs, LLC
Investigators
- Principal Investigator: Alexis Ogdie-Beatty, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 851448