- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04168619
MTX-related Liver Toxicity in Psoriasis Patients, Using Ultrasound-based Techniques as a Diagnostic Tool
Methotrexate-related Liver Toxicity in Psoriasis Patients, Using Ultrasound-based Techniques as a Diagnostic Tool
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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. Short term rises in hepatic transaminases are well recognized with methotrexate, which is largely reversible. However, the insidious development of liver fibrosis and ultimately cirrhosis is of greater clinical concern given this may be irreversible with significant impact. Methotrexate-induced liver fibrosis is still a concern especially in patients who received high cumulative dose and those with comorbid risk factors such as diabetes and obesity. The prevalence of significant fibrosis and cirrhosis were reported to be 4.5 - 33.3% and 0 - 25.6%, respectively, in liver biopsy series of psoriasis patients on methotrexate. The results were so variable owing to the facts that many studies were old with poor reporting and variable histological scoring system making interpretation difficult.
According to the NICE guideline and British Association of Dermatologist's guideline ( 2016), liver biopsy remains the gold standard in the assessment of liver fibrosis, however, it is a relatively invasive procedure, with potential sampling error and inter-observer variability, leading to decreasing use of liver biopsy as routine for monitoring methotrexate hepatotoxicity . Non-invasive methods to assess liver fibrosis are therefore advocated, including serum indices as well as transient elastography.
Transient elastography has been shown to correlate well with liver fibrosis in chronic hepatitis and has been widely adopted as a noninvasive method to assess liver fibrosis in various chronic liver disease, but not yet in this specific Psoriasis patients on methotrexate. There is increasing trend to use transient elastography for detection of methotrexate-associated liver fibrosis. However, only few studies included adequate number of patients with concomitant liver biopsy and transient elastography. Data from a study including a relatively high number of patients with liver biopsy (24 psoriasis patients) reported successful scan rate of 83.3% and high negative predictive value of 88% for significant fibrosis. Alternative, Serum procollagen III level (PIIINP) for liver fibrosis is only available in selected specialist centres oversea but not in HK and is costly. Currently, psoriasis patients on methotrexate with cumulative dose of 3000mg of above are advised to have USG guided Fine-needle aspiration (FNA) liver biopsy to assess the presence of liver fibrosis with severity grading , according to American Academy of Dermatology Guideline in Methotrexate dosing. For patient with liver fibrosis grading of 3 a or above ( Roenigfk classification) , they are advised to stop methotrexate and switch to alternative medication. 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 these patients for a paired transient elastography assessment and liver biopsy.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Judy SHAM, MCoun
- Phone Number: +852 22556489
- Email: js83213@hku.hk
Study Contact Backup
- Name: Sze-man Wong, MSc
- Phone Number: +852 22555154
- Email: wongsm11@hku.hk
Study Locations
-
-
-
Central, Hong Kong
- Recruiting
- Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Hong Kong
-
Contact:
- Sze-man Wong, MSc
- Phone Number: +852 22555154
- Email: wongsm11@hku.hk
-
Contact:
- Judy Sham, Master
- Phone Number: +852 22556489
- Email: js83213@hku.hk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Patients with contraindications for liver biopsy e.g. bleeding tendencies
- Patients with known decompensated cirrhosis
- Pregnancy
- Unstable medical illness or active infection
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Transient elastography (TE)
All patients who had MTX taken
|
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.
|
Two dimensional shear wave elastography (2D SWE)
For patients who has cumulative more than 3.5g methotrexate
|
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
For patients who has cumulative more than 3.5g methotrexate and had 2D SWE done
|
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.
Once discontinued methotrexate, based on subject's clinical condition and prescribe alternative treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Detection rate
Time Frame: At the time of diagnostic procedure
|
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
Time Frame: At the time of diagnostic procedure
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate risk factors of liver fibrosis
Time Frame: At the time of diagnostic procedure
|
Subject's demographic information eg age gender, cumulative dose of MTX, duration of disease.
Presence of PsA and other comorbidities will be collected and assessed if there is any relationship of methotrexate induce liver injury.
|
At the time of diagnostic procedure
|
Relationship of cumulative methotrexate dose
Time Frame: At the time of diagnostic procedure
|
Use the relationship of cumulative methotrexate dose, TE score and liver biopsy grade to identify the best cut-off value of liver stiffness for advanced liver fibrosis in psoriasis patients on methotrexate
|
At the time of diagnostic procedure
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sze-man Wong, MSc, The University of Hong Kong
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Skin Diseases
- Liver Diseases
- Skin Diseases, Papulosquamous
- Fibrosis
- Psoriasis
- Liver Cirrhosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- UW 19-390
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Psoriasis
-
ProgenaBiomeRecruitingPsoriasis | Psoriasis Vulgaris | Psoriasis of Scalp | Psoriatic Plaque | Psoriasis Universalis | Psoriasis Face | Psoriasis Nail | Psoriasis Diffusa | Psoriasis Punctata | Psoriasis Palmaris | Psoriasis Circinata | Psoriasis Annularis | Psoriasis Genital | Psoriasis GeographicaUnited States
-
Clin4allRecruitingPsoriasis of Scalp | Psoriasis Nail | Psoriasis Palmaris | Psoriasis Genital | Psoriasis PlantarisFrance
-
Innovaderm Research Inc.CompletedScalp Psoriasis | Pustular Palmo-plantar Psoriasis | Non-pustular Palmo-plantar Psoriasis | Elbow Psoriasis | Lower Leg PsoriasisCanada
-
Centre of Evidence of the French Society of DermatologyRecruitingPsoriasis | Psoriasis Vulgaris | Psoriasis of Scalp | Psoriatic Plaque | Psoriasis Universalis | Psoriasis Palmaris | Psoriatic Erythroderma | Psoriatic Nail | Psoriasis Guttate | Psoriasis Inverse | Psoriasis PustularFrance
-
UCB Biopharma S.P.R.L.CompletedModerate to Severe Psoriasis | Generalized Pustular Psoriasis and Erythrodermic PsoriasisJapan
-
AmgenCompletedPsoriasis-Type Psoriasis | Plaque-Type PsoriasisUnited States
-
TakedaRecruitingGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
Janssen Pharmaceutical K.K.RecruitingGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
Eli Lilly and CompanyCompletedGeneralized Pustular Psoriasis | Erythrodermic PsoriasisJapan
-
Shanghai Huaota Biopharmaceutical Co., Ltd.RecruitingGeneralized Pustular Psoriasis (GPP)China
Clinical Trials on Discontinue methotrexate
-
The University of Texas Health Science Center,...CompletedRespiratory Distress Syndrome | Apnea of PrematurityUnited States
-
University of Illinois at ChicagoRecruitingMultiple MyelomaUnited States
-
University Health Network, TorontoUnknown
-
Loyola UniversityUnknownCardiovascular Diseases | ESRDUnited States
-
University of Colorado, DenverNational Institute of Nursing Research (NINR)CompletedCardiovascular Disease | Palliative MedicineUnited States
-
Hugo de Luca CorreaFederal University of São Paulo; Catholic University of BrasíliaCompletedQuality of Life | Inflammation | Muscle Weakness | Chronic Kidney Failure | Solid Organ Transplant Rejection
-
Aarhus University HospitalUniversity of AarhusCompleted
-
University of Texas Southwestern Medical CenterCompletedDiabetes Type 2
-
Asan Medical CenterActive, not recruitingHepatitis B, ChronicKorea, Republic of
-
Leiden University Medical CenterRecruitingDeep Vein Thrombosis | Venous Thromboembolism | Pulmonary Embolism | Venous ThrombosesNetherlands