MTX-related Liver Toxicity in Psoriasis Patients, Using Ultrasound-based Techniques as a Diagnostic Tool

NCT04168619 | Unknown

• 1 other identifier: UW 19-390
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Methotrexate is one of the commonly used conventional systemic treatment for moderate to severe psoriasis as well as psoriatic arthritis. It is also used as co-therapy with TNF-antagonists to improve efficacy and reduce neutralizing drug antibodies formation. Apart from the bone marrow suppression, which can largely be avoided with careful dosing, monitoring and avoidance of certain drug interaction, hepatotoxicity is one of the major side-effects. The prevalence of significant liver fibrosis in patients taking methotrexate is estimated to be 5% and cirrhosis 1-2%. The British Association of Dermatologist's guideline (2016) discussed a few non-invasive tests such as the amino-terminal peptide of procollagen III (PIIINP), Fibrotest and transient elastography. While PIIINP was recommended to be used in baseline and serial assessment, liver stiffness measurement by transient elastography is not yet widely used owing to lack of high-quality data. Transient elastography (TE) has been shown to correlate well with liver fibrosis and has been widely adopted as a non-invasive method to assess liver fibrosis in various chronic liver disease. Two-dimensional shear wave elastrography (2D SWE) is a novel ultrasound technique that combines shear wave elastography with traditional ultrasound imaging. Liver stiffness measurement can be performed under the guidance of high rate B-mode image, allowing real-time visualization of liver parenchyma and avoidance of non-target structures such as vessels or focal liver lesions. In view of the demand of a safer and reliable non-invasive test to detect advanced liver fibrosis in psoriasis patients receiving methotrexate, we propose to recruit at-risk patients for a paired TE and 2D SWE assessment and liver biopsy.

Conditions

Psoriasis; Liver Fibrosis

Keywords

Liver Fibrosis; Psoriasis; Methotrexate; Transient elastography; Two-dimensional shear wave elastrography

Outcome Measures

Primary Outcomes (2)

• Detection rate

  The meanTE value of psoriasis patients detected with liver injury (. Roenigk. Grade 3a) and liver fibrosis Roenigk grade 3b and above) Area under the receiver operating characteristic curve (AUROC) will be performed to assess if TE is capable of identifying patients with and without liver injury

  At the time of diagnostic procedure

• Performance characteristics

  Area under the receiver operating characteristic curve (AUROC) will be performed to assess if TE and Shear wave elastography( SW). is capable of identifying patients with and without liver injury

  At the time of diagnostic procedure

Secondary Outcomes (2)

• Evaluate risk factors of liver fibrosis

  At the time of diagnostic procedure

• Relationship of cumulative methotrexate dose

  At the time of diagnostic procedure

Study Arms (3)

Transient elastography (TE)

All patients who had MTX taken

Drug: Discontinue methotrexate

Two dimensional shear wave elastography (2D SWE)

For patients who has cumulative more than 3.5g methotrexate

Drug: Discontinue methotrexate

Liver biopsy

For patients who has cumulative more than 3.5g methotrexate and had 2D SWE done

Drug: Discontinue methotrexate; Other: Medication depends on clinical judgement

Interventions

Discontinue methotrexate DRUG

According to the international guideline, patients with Roenigk grade 3a which indicate methotrexate-induced liver injury may continue methotrexate with a repeat biopsy in 6 months. In patients with Roenigk grades 3b or 4, indicate significant liver fibrosis/cirrhosis, methotrexate should be discontinued.

Liver biopsy; Transient elastography (TE); Two dimensional shear wave elastography (2D SWE)

Medication depends on clinical judgement OTHER

Once discontinued methotrexate, based on subject's clinical condition and prescribe alternative treatment

Liver biopsy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with clinical diagnosis of psoriasis or psoriatic arthropathy treated with ≥ 3.5 grams of methotrexate in the past or currently

You may qualify if:

• Patients with psoriasis who are managed in the Dermatology or Dermatology-Rheumatology combined Clinic, Queen Mary Hospital, Hong Kong, will be identified. Patients with clinical diagnosis of psoriasis or psoriatic arthropathy treated with ≥ 3.5 grams of methotrexate in the past or currently will be recruited.

You may not qualify if:

• Patients with contraindications for liver biopsy e.g. bleeding tendencies
• Patients with known decompensated cirrhosis
• Pregnancy
• Unstable medical illness or active infection

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Hong Kong

Central, Hong Kong

RECRUITING

MeSH Terms

Conditions

Psoriasis; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sze-man Wong, MSc

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sze-man Wong, MSc

CONTACT

+852 22555154; wongsm11@hku.hk

Judy SHAM, MCoun

CONTACT

+852 22556489; js83213@hku.hk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Honorary Clinical Assistant Professor

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: November 19, 2019
• Study Start: June 10, 2019
• Primary Completion: December 31, 2020
• Study Completion: July 12, 2021
• Last Updated: July 24, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)