New Tool to Measure Methotrexate Adherence in Patients with RA

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Patients with hemophilia had lower median score on the Offer Self-Image Questionnaire compared with a control group.
The objective of this study was to improve treatment of patients with RA by developing and validating a tool to help clinicians identify and evaluate adherence to methotrexate.

A novel Methotrexate Experience Questionnaire (MEQ) was developed, tested, and found to be a reliable and valid tool to assess the adherence of patients with rheumatoid arthritis (RA) to oral methotrexate, according to study findings published in the Journal of Patient-Reported Outcomes.

The MEQ was developed based on a literature review, qualitative interviews with patients with RA to understand their adherence to methotrexate therapy, and rheumatologist-assisted pilot testing. Validation of the final MEQ was conducted using a multi-center retrospective cross-sectional study. Eligible patients were identified through the Optimum Patient Care Research Database (OPCRD), a large primary care database in the United Kingdom. Patients age 18 and older with RA and methotrexate prescriptions within the past 6 and 12 months were invited to participate.

Those who agreed to participate were asked to complete the MEQ, the Acceptance by the Patients of their Treatment questionnaire (ACCEPT; ranges from 0 to 100 with higher scores indicating greater medication acceptance), and the Routine Assessment of Patient Index Data 3 (RAPID-3; ranges from 0-30, with higher scores indicating greater disease activity). The Proportion of Days Covered (PDC) for each patient was calculated from prescription data and was used to identify adherent patients (those with 80% or more days in the time period covered by the prescription).

During development of the MEC, the following barriers to methotrexate adherence were identified:

  • Physical barriers (pain, exhaustion, hospitalization)
  • Financial barriers (cost of treatment, no insurance)
  • Practical barriers (difficulty taking medication, too many visits to doctors, too many treatments, problems refilling medication, lack of knowledge about treatment)
  • Cognitive barriers (forgetting to take medication)
  • Perceptual barriers (dislike for taking medication or beliefs that medication was harmful or ineffective)
  • Emotional barriers (stress, frustration, fear, lack of confidence to continue treatment)
  • Side effects

The final MEQ included 24 items across 5 domains (benefits, convenience, drivers of noncompliance, negative feelings, and my opinion about my care) rated on 4-point Likert scales.

The cross-sectional study and analysis included 307 patients. Cronbach’s alpha, which measures the internal consistency reliability (the extent to which items within the same dimension are consistent with each other), was 0.87 and supported the validity of the MEQ. The researchers found a significant correlation between MEQ total scores and ACCEPT scores (0.55; P <0.001).  The MEQ was also able to discriminate between patients groups with different levels of adherence. Patients with 12-month PDC scores of 80% or higher had significantly higher MEQ scores compared with those with PDC scores of less than 80% (82.7 vs. 76.3, respectively; P <0.0001). In addition, lower MEQ scores were reported by patients with more severe disease as measured by the RAPID-3.

Limitations of the study included the retrospective study design and the relatively low response rate of patients who were invited to participate (30%) which may have selected for more adherent patients. In addition, the MEQ was validated in the United Kingdom and may have limited application to other countries particularly around the issue of insurance coverage.

The researchers concluded, “The MEQ appears to be a valid instrument to assess the adherence of patients taking [methotrexate] in RA and should help clinicians in daily medical practice to guide their discussions and make better-informed joint treatment decisions with their patients.” They continued, “Collecting patient experience with [methotrexate] in a systematic and standardized way using the MEQ will likely contribute to the recommended shared decision-making (SDM) process which is advocated in rheumatoid arthritis (RA), although not always observed in clinical practice.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Curtis JR, Nebesky JM, de Bock E, et al. Development and validation of the methotrexate experience questionnaire, a new methotrexate oral treatment adherence tool in rheumatoid arthritis. Journal of Patient-Reported Outcomes. Published online August 9, 2021. doi:10.1186/s41687-021-00339-5