Clinical trial NCT02174354: Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis
Official title: Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Psoriasis Chronic
Injury of Liver
Keywords: Psoriasis
Methotrexate
Methotrexate Polyglutamates
Injury of Liver
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2014-06-25
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with psoriasis taking methotrexate recruited in outpatient dermatology clinics

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Serial erythrocyte methotrexate polyglutamate measurements using high performance liquid chromotography
timeFrame: From 3 months to 5 years after commencing methotrexate
Secondary outcomes:
measure: Alanine transaminase (ALT) and Full blood count (FBC) will be used to measure toxicity to methotrexate
timeFrame: 3 months to 5 years after first MTX dose
Other outcomes:
measure: A ROC (Receiver Operating Characteristic) curve will be produced in order to define a therapeutic dose range of MTXPG in psoriasis
timeFrame: 3 months to 5 years after first dose of methotrexate
Locations:
city: London
country: United Kingdom
facility: King's College London and Guys' and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Kings College London and Guys and St Thomas' NHS Foundation Trust
name: Catherine H Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.