Liver Fibrosis and Gut Microbiota in Patients With Psoriasis Vulgaris and Rheumatoid Arthritis on Methotrexate

A Comparison Study of Liver Fibrosis and Its Association With Gut Microbiota in Patients With Psoriasis Vulgaris and Rheumatoid Arthritis on Methotrexate

While methotrexate (MTX) remains a treatment of choice for patients with rheumatoid arthritis (RA), psoriasis (PsO) and psoriatic arthritis (PsA), long-term MTX use has been shown to be associated with liver fibrosis and cirrhosis in these patients. In addition, gut dysbiosis has been found to be associated with liver fibrosis and cirrhosis via the gut-liver axis, underscoring the potential role of gut microbiota and bacterial translocation in the pathogenesis of chronic liver diseases in these patients.

In this study, we aim to assess the prevalence of advanced liver fibrosis or cirrhosis among these patients on MTX treatment compared to those without, using transient elastography. We also aim to identify the possible risk factor(s) for advanced liver fibrosis or cirrhosis among them. Further, we aim to characterize the difference in fecal microbiota patterns among these three groups of patients.

Using a cross-sectional, prospective cohort design, this study will enroll approximately 600 eligible patients, including 300 patients with PsO/PsA and 300 patients with RA, to examine the following hypotheses:

1. Patients on higher cumulative dose of MTX will have higher prevalence of advanced liver fibrosis or cirrhosis compared to those on lower cumulative dose of MTX;
2. Patients with MTX use will have higher prevalence of advanced liver fibrosis or cirrhosis compared to those without MTX use;
3. The fecal microbiota composition will be different between patients with and without MTX treatment; and
4. The fecal microbiota composition will be different between patients with and without advanced fibrosis/cirrhosis while on MTX treatment.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis; Psoriasis Vulgaris; Fibrosis, Liver

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients who have regular follow up in Dermatology/ Rheumatology clinics of Queen Mary Hospital, with a diagnosis of PsO/PsA and/or RA will be identified and screened for eligibility.

Description

Inclusion Criteria:

• Age between 18 to 85 years
• Have regular follow up in Dermatology/ Rheumatology clinics of Queen Mary Hospital
• Diagnosed with PsO/PsA or RA
• Chinese ethnicity

Exclusion Criteria:

• Age below 18 years or above 85 years
• Known decompensated cirrhosis
• Pregnancy or breastfeeding
• Unstable medical illness or active infection
• Unable to provide written consent
• Unable to adhere to the protocol
• Unable to read and/or write Chinese language
• On anticoagulant/ antiplatelet treatment
• Abnormal platelet count <150
• Known disease/condition with prolonged INR/bleeding tendency

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
PSO/PSA; Patients diagnosed with psoriasis or psoriatic arthritis
RA; Patients diagnosed with rheumatoid arthritis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with advanced liver fibrosis or cirrhosis	We will measure the number of patients with significant fibrosis (defined as having liver stiffness ≥ 7.5 kPa in transient elastography), and among those who undergo biopsy, the number of patients whose biopsy specimen is of Roenigk grades 3b or 4	At the time of the assessment procedure
The type and abundance of fecal microbiota patterns	We will measure the type and abundance of various bacteria/viruses in specimens; alpha diversity within a specimen and beta diversity between groups of specimen; specific taxa that differ significantly between groups; and metabolic profiles and functional pathways associated with change in gut microbiota	At the time of the assessment procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The risk factors of liver fibrosis	Risk factors to be examined will include demographic variables such as age and gender, cumulative dose of MTX, gut dysbiosis, duration of disease, co-morbidities, hepatic steatosis, liver stiffness, and other potential factors	At the time of the assessment procedure

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Sze-Man Wong, MSc, MRCP, Queen Mary Hospital, Hong Kong

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 13, 2020
• Primary Completion (ANTICIPATED): December 12, 2021
• Study Completion (ANTICIPATED): December 11, 2022

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (ACTUAL): July 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Methotrexate; Microbiota
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Liver Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Fibrosis; Arthritis; Arthritis, Rheumatoid; Psoriasis; Liver Cirrhosis
• Other Study ID Numbers: UW19-839

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No