Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis

Psoriasis Chronic Clinical Trial

— MTXPG  

Official title:

Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02174354
• Other study ID #: 11/H0802/7
• Status: Enrolling by invitation
• Phase: N/A
• First received: May 22, 2014
• Last updated: June 24, 2014
• Start date: January 2011
• Est. completion date: August 2018

Study information

• Verified date: June 2014
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

Methotrexate (MTX) is widely prescribed to treat inflammatory conditions including psoriasis, where it is the recommended first-line systemic therapy in moderate-to-severe disease. Approximately 40% of patients with psoriasis have a sub-optimal response to MTX and a significant number experience side effects that may include deranged liver enzymes. There is currently no validated test to predict how patients with psoriasis will respond to MTX, in terms of disease outcome and/or toxicity, or to guide dose escalation in this group.

Description:

Data for this study is drawn from the BSTOP (Biomarkers of Systemic Treatment Outcomes in Psoriasis) cohort. This is a multi-centre, prospective, cohort study to establish clinically relevant biomarkers and pharmacogenetic markers of systemic treatment outcomes in patients with severe psoriasis.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 350
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with psoriasis

• Taking oral or subcutaneous methotrexate

• Measurement of methotrexate polyglutamates on at least one occasion during therapy.

• Patients who have given written informed consent

Exclusion Criteria:

• Unable to consent

• Not taking methotrexate

Study Design

Observational Model: Cohort

Related Conditions & MeSH terms

• Injury of Liver
• Psoriasis
• Psoriasis Chronic

Locations

Country	Name	City	State
United Kingdom	King's College London and Guys' and St Thomas' NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Becker ML, Gaedigk R, van Haandel L, Thomas B, Lasky A, Hoeltzel M, Dai H, Stobaugh J, Leeder JS. The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response. Arthritis Rheum. 2011 Jan;63(1):276-85. doi: 10.1002/art.30080. — View Citation

Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Frampton C, James J, Barclay ML. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. Arthritis Rheum. 2009 Aug;60(8):2248-56. doi: 10.1002/art.24653. — View Citation

Woolf RT, West SL, Arenas-Hernandez M, Hare N, Peters van Ton AM, Lewis CM, Marinaki AM, Barker JN, Smith CH. Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study. Br J Dermatol. 2012 Jul;167(1):165-73. doi: 10.1111/j.1365-2133.2012.10881.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	A ROC (Receiver Operating Characteristic) curve will be produced in order to define a therapeutic dose range of MTXPG in psoriasis	If a positive correlation is identified between MTXPG levels and clinical response we aim to define a therapeutic dose range of MTXPG.	3 months to 5 years after first dose of methotrexate	Yes
Primary	Serial erythrocyte methotrexate polyglutamate measurements using high performance liquid chromotography	To determine if there is a correlation between methotrexate polyglutamate concentrations and clinical response measured by Psoriasis Area Severity Index( PASI) in patients on methotrexate monotherapy with psoriasis. This will consider potential confounding factors, including age, gender and dose of MTX	From 3 months to 5 years after commencing methotrexate	No
Secondary	Alanine transaminase (ALT) and Full blood count (FBC) will be used to measure toxicity to methotrexate	To determine if there is an association between MTXPG levels and evidence of hepatotoxicity in patients with psoriasis taking either (1) methotrexate alone or (2) methotrexate in combination with another systemic drug. Evidence of hepatotoxicity will be determined by the use of current gold standard tests.	3 months to 5 years after first MTX dose	Yes

External Links

•   Skin Therapy Research Unit Website