Guselkumab vs Golimumab for Psoriatic Arthritis

(EVOLUTION Trial)

Recruiting at 13 trial locations

Overseen By Jessica Walsh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Pennsylvania

Must be taking: TNFi, OSM/csDMARDs

Must not be taking: Golimumab, IL12/23i, IL17i, IL23i

Disqualifiers: Pregnancy, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 months

150 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of any oral small molecule drugs, NSAIDs, glucocorticoids (less than 10 mg daily), or topical medications for psoriasis that you are currently using. You must have been on this stable dose for at least 4 weeks before starting the trial and continue it during the study.

What data supports the effectiveness of the drugs Guselkumab and Golimumab for treating psoriatic arthritis?

Research shows that Golimumab is effective for psoriatic arthritis, especially for patients who did not respond to other similar treatments. Guselkumab has also shown positive results in improving symptoms in psoriatic arthritis and has been effective in treating plaque psoriasis, which is related to psoriatic arthritis. ^{1 2 3 4 5}

Is Guselkumab or Golimumab safe for humans?

Golimumab has been studied for safety in conditions like rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, with data suggesting it is generally safe for human use. However, specific safety data for Guselkumab in this context is not provided in the available research. ^{2 6 7 8 9}

How does the drug Guselkumab differ from other treatments for psoriatic arthritis?

Guselkumab is unique because it specifically targets the interleukin-23 (IL-23) pathway, which is different from many other treatments that target tumor necrosis factor (TNF). This makes it a novel option for patients who do not respond well to TNF inhibitors. ^{3 10 11 12 13}

Research Team

Alexis Ogdie-Beatty, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults aged 18-80 with active psoriatic arthritis who have not responded well to TNF inhibitors. Participants must have at least one active psoriasis plaque and meet specific criteria for joint swelling or tenderness. They should be on a stable dose of certain medications if used, but cannot be pregnant, trying to conceive, or have had serious reactions to similar drugs.

Inclusion Criteria

I am on a stable dose of one specific oral medication for my condition.

I have at least one active psoriasis plaque.

I have been diagnosed with psoriatic arthritis according to CASPAR criteria.

Exclusion Criteria

I have previously been treated with golimumab or similar medications.

I am taking more than 10 mg of steroids daily.

Currently pregnant or actively trying to conceive

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either guselkumab or golimumab based on randomization to assess effectiveness in PsA patients with inadequate response to TNFi

12 months

Visits every 4 or 8 weeks depending on treatment group

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Golimumab
• Guselkumab
• Placebo

Trial Overview The study compares the effectiveness of two treatments in patients with PsA who haven't done well on TNF inhibitors: Guselkumab (an IL23 inhibitor) versus Golimumab (a second TNFi). It's a randomized double-blind trial where participants won't know which treatment they're getting.

Participant Groups

Group I: Guselkumab 100mg q8w Experimental Treatment 1 Intervention

Guselkumab (GUS) 100mg every 8 weeks

Group II: Guselkumab 100mg q4w Experimental Treatment 1 Intervention

Guselkumab (GUS) 100mg every 4 weeks

Group III: Golimumab 50mg q4w Active Control 1 Intervention

Golimumab (GOL) 50mg every 4 weeks

Golimumab is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Simponi for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Ulcerative colitis

Approved in United States as Simponi for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Ulcerative colitis

Approved in Canada as Simponi for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Ulcerative colitis

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

In a pooled analysis of 712 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), second-line treatment with golimumab (GLM) achieved low disease activity in 58.3% of RA patients and around 45% in PsA and axSpA patients after 6 months, indicating its effectiveness as a treatment option.

The treatment was well-tolerated, with a 12-month persistence rate of 67.8% and no new safety concerns reported, suggesting that GLM is a safe and viable second-line therapy for patients who did not respond to first-line TNFα inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie. Govoni, M., Batalov, A., Boumpas, DT., et al.[2023]

In a study of 410 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), golimumab demonstrated a two-year retention rate of 47.3% for RA, 48% for PsA, and 62.8% for AS, indicating better long-term use in AS patients.

Patients with RA who received golimumab alongside conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) had a lower discontinuation rate compared to those on golimumab alone, suggesting that combination therapy may enhance treatment retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year retention rate of golimumab in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: data from the LORHEN registry. Manara, M., Caporali, R., Favalli, EG., et al.[2017]

Guselkumab is an effective treatment for moderate to severe plaque psoriasis, showing superior results compared to placebo and adalimumab in the VOYAGE trials, with benefits maintained for up to 2 years.

Patients who previously did not respond well to ustekinumab showed significantly better outcomes when switched to guselkumab, indicating its efficacy in treatment-resistant cases, while also improving overall quality of life and being well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis. Al-Salama, ZT., Scott, LJ.[2019]

In a real-world study of 1454 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), golimumab (GLM) showed significant effectiveness as a treatment regardless of whether it was used as a first, second, or third-line biologic agent.

After 24 months of treatment, remission rates for RA patients were 45.3% for first-line, 50.0% for second-line, and 33.3% for third-line users, while PsA patients had a response rate of 76.4% for first-line use, demonstrating GLM's efficacy across different treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golimumab as the First-, Second-, or at Least Third-Line Biologic Agent in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis: Post Hoc Analysis of a Noninterventional Study in Germany. Krüger, K., Burmester, GR., Wassenberg, S., et al.[2021]

In a study of 246 patients with psoriatic arthritis and imaging-confirmed sacroiliitis, guselkumab treatment led to significant and durable improvements in axial symptoms and disease activity over 2 years, with many patients achieving at least a 50% improvement in their symptoms.

At week 100, approximately 49-54% of patients treated with guselkumab achieved a BASDAI 50 response, indicating substantial effectiveness, regardless of sex or HLA-B*27 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study. Mease, PJ., Gladman, DD., Poddubnyy, D., et al.[2023]

In a systematic review of 10 RCTs and 51 observational studies, infliximab was associated with a higher risk of treatment discontinuation and serious infections compared to abatacept, adalimumab, and etanercept in patients with rheumatoid arthritis (RA).

The safety profile of targeted immunomodulators generally favored abatacept, adalimumab, and etanercept over infliximab, although there was insufficient evidence to compare other TIMs or assess safety outcomes in non-RA populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. Desai, RJ., Thaler, KJ., Mahlknecht, P., et al.[2022]

In a study of 1318 patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, GP2017 (Hyrimoz) showed a lower risk of withdrawal compared to SB5 (Imraldi), with a hazard ratio of 0.60, indicating better retention of treatment.

Patients using GP2017 also had a higher remission rate at 6 months (OR 1.72) compared to those on SB5, suggesting that GP2017 may be more effective in routine care for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial. Nabi, H., Georgiadis, S., Loft, AG., et al.[2021]

In a study of 603 patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis, over 93% successfully transitioned from the reference drug adalimumab (ADA) to the biosimilar Amgevita® (ADAbio) without significant changes in disease activity or safety, supporting the bioequivalence of the two medications.

Only 6.6% of patients switched back to ADA, indicating that the majority tolerated the switch well, and any reported symptoms likely stemmed from nocebo effects rather than actual disease flare-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Non-medical Switch from Reference Adalimumab to Biosimilar Adalimumab is Highly Successful in a Large Cohort of Patients with Stable Inflammatory Rheumatic Joint Diseases: A Real-Life Observational Study. van Adrichem, RCS., Voorneveld, HJE., Waverijn, GJ., et al.[2022]

Tofacitinib has a consistent safety profile in psoriatic arthritis (PsA) similar to that observed in rheumatoid arthritis (RA), based on a review of 73,525 adverse event reports, with 5,394 cases related to PsA.

The analysis showed that the reporting rates for adverse events were higher for the modified release formulation compared to the immediate release, indicating potential differences in safety profiles based on the formulation used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. Burmester, GR., Coates, LC., Cohen, SB., et al.[2023]

Guselkumab is an approved treatment for moderate-to-severe plaque psoriasis, specifically designed to inhibit interleukin 23 (IL-23), which plays a key role in the inflammatory process of the disease.

By blocking IL-23 from binding to its receptor, guselkumab disrupts the IL-17 pathway, which is crucial for the activation of type 17 helper T cells, thereby reducing inflammation and symptoms in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: First Global Approval. Markham, A.[2019]

In the phase 3b COSMOS trial, guselkumab, an IL-23 inhibitor, was effective in reducing disease activity in adults with active psoriatic arthritis who had inadequate responses to tumor necrosis factor inhibitors, showing significant decreases in inflammatory markers like CRP and IL-17 levels by Week 24.

Participants treated with guselkumab exhibited a notable improvement in clinical response, with higher baseline levels of IL-22 and IFNɣ associated with better outcomes, indicating a potential biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study. Schett, G., Chen, W., Gao, S., et al.[2023]

In a phase 2a trial involving 149 patients with active psoriatic arthritis, guselkumab significantly improved symptoms, with 58% of patients achieving at least a 20% improvement in their condition compared to only 35% in the placebo group, demonstrating its efficacy as a treatment.

Guselkumab was well tolerated over 44 weeks, with a similar rate of adverse events (36% in the treatment group vs. 33% in the placebo group), indicating a favorable safety profile for this novel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Deodhar, A., Gottlieb, AB., Boehncke, WH., et al.[2020]

Guselkumab is an effective treatment for moderate-to-severe psoriasis, showing significant improvements in skin condition and quality of life in clinical trials, and is generally well tolerated by patients.

In head-to-head trials, guselkumab outperformed adalimumab and secukinumab in achieving higher response rates for psoriasis severity, indicating its superior efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab for the treatment of adults with moderate to severe plaque psoriasis. Puig, L.[2020]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Two-year retention rate of golimumab in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: data from the LORHEN registry. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Golimumab as the First-, Second-, or at Least Third-Line Biologic Agent in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis: Post Hoc Analysis of a Noninterventional Study in Germany. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The Non-medical Switch from Reference Adalimumab to Biosimilar Adalimumab is Highly Successful in a Large Cohort of Patients with Stable Inflammatory Rheumatic Joint Diseases: A Real-Life Observational Study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Guselkumab: First Global Approval. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Guselkumab for the treatment of adults with moderate to severe plaque psoriasis. [2020]