Guselkumab for Psoriatic Arthritis

Overseen By Mehrnaz Aghili

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must be taking: Guselkumab

Must not be taking: Corticosteroids, Estrogen, Tamoxifen, others

Disqualifiers: Hepatitis B, Hepatitis C, Cirrhosis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must not have changed your regular medication regimen in the last three months and cannot have used systemic or chronic steroids in the 8 weeks before the study.

What data supports the effectiveness of the drug Guselkumab for treating psoriatic arthritis?

Guselkumab has been shown to be effective in treating moderate-to-severe plaque psoriasis, and studies have also evaluated its use in patients with psoriatic arthritis, showing positive results in improving symptoms like enthesitis (inflammation where tendons or ligaments attach to bone) and dactylitis (swelling of fingers or toes). ^{1 2 3 4 5}

Is Guselkumab safe for humans?

Guselkumab has been generally well tolerated in studies for conditions like plaque psoriasis and psoriatic arthritis, with safety data pooled from multiple studies showing it is safe for up to 2 years of use. ^{1 2 3 6 7}

What makes the drug Guselkumab unique for treating psoriatic arthritis?

Guselkumab is unique because it specifically targets and blocks interleukin-23 (IL-23), a protein involved in inflammation, by binding to its p19 subunit. This makes it different from other treatments that may not target IL-23 as selectively, offering a novel approach for patients with psoriatic arthritis, especially those who have not responded well to other treatments like tumor necrosis factor inhibitors. ^{1 2 3 8 9}

What is the purpose of this trial?

While many studies examine Nonalcoholic fatty liver disease (NAFLD), little is known about its progression to high-risk nonalcoholic steatohepatitis (NASH) in PsA patients. Shared disease mechanisms may explain the increased severity in PsA. This study involves two visits from PsA patients with NAFLD and active disease signs (e.g., swollen joint, enthesitis, or psoriatic plaque). It aims to assess the impact of biological therapies on liver disorders, joints, and skin in PsA patients.

Eligibility Criteria

This trial is for patients with Psoriatic Arthritis (PsA) who also have Nonalcoholic fatty liver disease (NAFLD). Participants should show active signs of PsA, like swollen joints or skin plaques. Specific eligibility criteria are not provided, but typically include factors like age, overall health, and the severity of conditions.

Inclusion Criteria

I am starting Guselkumab for Psoriatic Arthritis as recommended by my rheumatologist.

My regular medications have been the same for the last 3 months and I haven't taken steroids in the last 8 weeks.

Overweight or obese by BMI ≥ 25.0 kg/m2 or ≥ 23.0 for Asian participants

Exclusion Criteria

I do not have chronic liver disease, HIV, or plan to become pregnant, and my life expectancy is over 5 years.

I have been treated with specific immune-targeting drugs or more than 2 TNF blockers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Guselkumab therapy to assess its impact on NAFLD and PsA

24 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Guselkumab

Trial Overview The study tests Guselkumab therapy's effects on NAFLD and PsA severity. It involves two visits from participants to assess how this biological therapy impacts liver health as well as joint and skin symptoms associated with PsA.

Participant Groups

Group I: psoriatic arthritis patients Experimental Treatment 1 Intervention

Adults with active PsA and diagnosed NAFLD

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

Approved in United States as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Approved in European Union as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

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

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]

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 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]

In a study of 285 adults with psoriatic arthritis who had previously not responded to tumor necrosis factor inhibitors, guselkumab significantly improved joint symptoms, with 44.4% of patients achieving a 20% improvement in their condition (ACR20) compared to 19.8% in the placebo group at week 24.

Guselkumab demonstrated a favorable safety profile, with low rates of serious adverse events (3.7%) and no deaths or opportunistic infections reported, indicating it is a safe treatment option for patients with TNFi-resistant psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS). Coates, LC., Gossec, L., Theander, E., et al.[2022]

In a phase II trial involving 149 patients with active psoriatic arthritis, guselkumab significantly improved symptoms of enthesitis and dactylitis compared to placebo, with these improvements sustained through week 56.

Patients who switched from placebo to guselkumab treatment experienced similar benefits in enthesitis and dactylitis as those who received guselkumab from the start, indicating its effectiveness regardless of when treatment began.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study. Mease, PJ., Gladman, DD., Deodhar, A., et al.[2021]

Guselkumab (GUS) demonstrated a favorable safety profile in patients with psoriatic arthritis (PsA), showing low adverse event (AE) rates for both TNFi-naïve (139.7/100 patient-years) and TNFi-experienced patients (174.0/100 patient-years) over a period of up to 2 years.

The safety outcomes, including rates of serious AEs and treatment discontinuation, were consistent between GUS-treated patients and those receiving placebo, indicating that GUS is a safe treatment option for PsA regardless of prior TNFi use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. Rahman, P., Boehncke, WH., Mease, PJ., et al.[2023]

In the DISCOVER-2 trial, guselkumab was tested in biologic-naive patients with active psoriatic arthritis, demonstrating significant efficacy in reducing disease activity compared to placebo.

The study's double-blind, randomized, placebo-controlled design ensures robust results, highlighting guselkumab as a promising treatment option for patients who have not previously received biologic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab safely improved clinical outcomes in biologic-naive patients with psoriatic arthritis. Schattner, A.[2020]

Guselkumab is a human monoclonal antibody that selectively blocks IL-23, which is important in the development of psoriasis and psoriatic arthritis, and it was approved for treating active psoriatic arthritis based on data from two phase-3 studies (DISCOVER-1 and -2).

This treatment represents a new therapeutic option for patients with active psoriatic arthritis, demonstrating both efficacy and safety, and it is the first selective IL-23 inhibitor to receive FDA approval for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults. Boehncke, WH., Brembilla, NC., Nissen, MJ.[2021]

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]

References

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

Guselkumab: First Global Approval. [2019]

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

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

3. 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]

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

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS). [2022]

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

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study. [2021]

6. Canada pubmed.ncbi.nlm.nih.gov

Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis. [2023]

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

Guselkumab safely improved clinical outcomes in biologic-naive patients with psoriatic arthritis. [2020]

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

Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults. [2021]

9. 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]