Elucidating Shared Mechanisms Contributing to NAFLD and PsA Disease Severity With Guselkumab Therapy

Launched by UNIVERSITY OF CALIFORNIA, SAN DIEGO · Sep 3, 2024

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ClinConnect Summary

This clinical trial is looking into how a medication called Guselkumab can help patients with Psoriatic Arthritis (PsA) who also have Nonalcoholic Fatty Liver Disease (NAFLD). Researchers want to understand the shared factors that make both conditions worse. The study will involve two visits for participants who have active signs of PsA, such as swollen joints or skin plaques. The goal is to see how Guselkumab affects not only the joints and skin but also the liver health of these patients.

To be eligible for this trial, participants need to be adults diagnosed with PsA, have at least one swollen joint or active skin plaque, and be starting Guselkumab therapy as recommended by their doctor. They should also have elevated liver fat consistent with NAFLD and meet certain health criteria, like being overweight or obese. Participants will not be able to change their medications for three months before the trial, and they should not have any other serious liver issues. If you or a loved one qualifies, joining this study could provide valuable insights into managing both PsA and liver health.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Adults with diagnosis of PsA fulfilling the classification for PsA (CASPAR) criteria.
• 2. Must have:
• • 1 or more swollen joint(s) and/or one or more active sites of enthesitis
• • 3. AND/OR
• • 1 or more psoriatic plaques
• • 4. No changes in the regular medication regimen within the last three months, and no use of systemic and/or chronic steroids within 8 weeks leading up to the study.
• • 5. Overweight or obese by BMI ≥ 25.0 kg/m2 or ≥ 23.0 for Asian participants
• • 6. Patients are starting Guselkumab therapy for PsA as indicated by primary rheumatologist
• • 7. Elevated liver fat on controlled attenuation parameter (CAP) ≥ 288 dB/m, which is consistent with NAFLD after exclusion of secondary causes of liver disease.
• Exclusion Criteria:
• • 1. Patients with prior exposure to IL12/23i, IL-17i, JAKi, or TYK2i. Patients with exposure to more than 2 TNFi.
• • 2. Evidence of other causes of chronic liver disease
• • Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
• • Previous or current infection with Hepatitis C as defined by presence of hepatitis C virus Abin serum (anti-HCV Ab).
• • Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
• • Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
• • Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
• • Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
• • Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
• • Drug-induced liver disease as defined on the basis of typical exposure and history.
• • Bile duct obstruction as shown by imaging studies.
• • History of gastrointestinal bypass surgery or ingestion of medications known to produce steatosis, such as corticosteroids, high-dose estrogen, tamoxifen, amiodarone or tetracycline in the previous 6 months.
• • Evidence of cirrhosis or previously known cirrhosis based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices
• • Presence of regular and/or excessive use of alcohol (defined as \>30g/day for males and \>15g/day for females) for a period longer than 2 years at any times in the last 10 years
• • Serum creatinine \> 2.0 mg/dL
• • The subject is a pregnant or nursing female or is planning to become pregnant
• • Life expectancy less than 5 years
• • 3. History of known HIV infection