Methotrexate Use Improvement in Rheumatoid Arthritis Using Biomarker Feedback

Study Overview
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Brief Summary
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The study is a prospective single-centre randomised controlled trial to examine the feasibility of a fully powered randomised controlled trial to examine if HPLC-SRM-MS guided intervention is superior to standard clinical care in improving clinical, behavioural and health-economy outcomes in RA patients prescribed MTX. The trial will consist of 4 stages: Screening ( -2 weeks) Recruitment, consent, randomisation, data collection, examination and blood sampling - baseline visit 1 (time point 0) Intervention - telephone appointment (visit 2, intervention arm) Outcome - visit 3 Process evaluation - visit 4 Prior to any trial specific procedures, the participant must have signed the informed consent form (ICF). The trial will offer a small financial compensation for successfully recruited patients toward the costs of parking/refreshments/travel costs/inconvenience related to attending visits

Detailed Description
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Rheumatoid arthritis (RA) affects up to 1% of the adult population. It is a condition that is treatable by medications. Methotrexate (MTX) is the first-line therapy for RA however, up to 60% of patients prescribed MTX still have active RA. This puts these patients at higher risk of joint damage compared to those whose RA is under control. One important explanation for the poor control in those who receive treatment is that some patients, for many reasons, do not take their medications as recommended (non-adherence). Non-adherence is associated with increased costs to the NHS and reduced response to MTX. The study will assess whether it is achievable to conduct a much larger study to explore whether a review of how well patients are coping with MTX can improve RA control. Understanding the reasons for poor RA control has the potential to improve the health and well-being of individual patients, avoid unnecessary tests and hospital appointments and save money in healthcare. The trial will recruit 50 patients with RA who have been prescribed MTX for more than 2 years. 25 patients will be asked to donate blood samples and complete questionnaires, but their treatment will continue as standard. The blood tests will include patients MTX levels. The results of the test provide a direct measure of medication adherence. For the other 25 patients, the results of the blood tests will be fed back to them with tailored targeting of the main reason(s) for the deviation from the prescribed MTX. At the end of the study, the investigators will assess the feasibility of a randomised controlled trial of a biochemical screening of adherence guided intervention in patients with RA treated with MTX.

Official Title
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Methotrexate Use Improvement in Rheumatoid Arthritis Using Biomarker Feedback: A Feasibility Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Drug level blood tests
* Other: Telephone Interview


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prescribed oral MTX for ≥ two years Clinical diagnosis of RA Have a telephone Male or female aged 18 years or above Exclusion Criteria: Patients with significant psychiatric illness as determined by the clinician Patients unable to attend second appointment Patients unable to provide informed consent Patients with recent changes in the prescribed anti-rheumatic medications within 2 weeks of visit 1 Unable to speak English and complete questionnaires

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Outcome of blood test provided<br>These patients are given the results of their drug level blood tests and treatment can be altered/ further advice can be provided as a result of this. | Other: Drug level blood tests<br>* All information included previously.<br>|
| No Intervention: Outcome of blood test not provided<br>The blood results for these people are not fed back to the patient or the clinical site. | |
| Experimental: Patients have a telephone interview<br>All patients are randomised for a second time; 20% (10) of them will have a semi-structured phone interview | Other: Telephone Interview<br>* All information included previously.<br>|
| No Intervention: No telephone interview<br>All patients are randomised for a second time; 80% won't have a phone call and this will be as per standard care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Power for full randomized controlled trial | Change in proportion of people who adhere over 3 months | 3 months | 
| Patient opinion of HPLC-SRM-MS guided intervention using semi-structured interviewing |  | 1 year | 
| Patient opinion of process of research, including outcome measures using semi-structured patient interviewing |  | 1 year | 
| Number of patients correctly having intervention according to allocation |  | 1 year | 
| Recruitment time | Length of time study needs to run for to recruit all participants | 1 year | 
| Number of patients invited to take part in the study and number of patients recruited |  | 1 year | 
| Withdrawal rate |  | 1 year | 
| Trial cost |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical adherence | MTX quantified with HPLC-SRM-MS from serum. | 1 year | 
| DAS-28 at baseline and 3 months | The disease activity score-28 (DAS-28), range 2-10, higher values represent worse disease activity. | 1 year | 
| Quantity of patient encounters | Number of patient encounters with healthcare professionals per patient. | 1 year |