Methotrexate Adherence Rates Improve After Implementation of New Strategies

January 26, 2021
Lana Dykes

Despite the limitations of the study, non-adherence rates were significantly reduced in patients observed throughout the 3 years, indicating that the methods developed and deployed were successful.

Adherence rates for patients with rheumatoid arthritis (RA) taking methotrexate (MTX) can be improved with simple techniques including drug education and messaging. Simple reminders about the benefits of treatment and warnings of adverse reactions associated with non-adherence, in conjunction with motivational interviewing (MI), cumulatively halved non-adherence rates in a UK study published in the Oxford Rheumatology journal.1

MTX is the “cornerstone” therapy for patients with RA, but a drug will never be able to reach its full potential if it is not taken consistently, meaning that improving adherence rates is a priority in order for patients to obtain the best results possible.

But it goes beyond individual health benefits, investigators explain. “Given that failure to respond to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is part of the eligibility criteria for biologic therapies in the UK, and given the cost differential of MTX compared with biologic drugs, there is a health economic argument to optimize adherence to MTX in order to reduce health costs,” the research team wrote.

Investigators created a team consisting of 2 rheumatologists, an academic clinical lecturer in rheumatology, a health psychologist, and a senior specialist nurse. The group developed an anonymous self-report questionnaire to capture patients’ non-adherence information. The data were collected for 3 months prior to the official start of the study, monthly for the subsequent 2 years, and then sporadically during the third year. In order to test adherence to MTX, investigators utilized both the questionnaire, as well as a biochemical assay to measure MTX serum levels (tested before and 2.8 years after introducing the changes).

The first step in understanding the potential barriers to adherence was to create a process map. This outlined the pathway from prescribing MTX to establishing therapy. Next, staff members were required to take mandatory MI trainings to learn the “patient-centered consultation technique designed to elicit the patient’s own goals and plans for behavior change.” Physicians were able to schedule 1:1 drug education consultations for patients with whom they had concerns regarding non-adherence. An “agenda-setting tool” was developed but was later discarded as patients did not find it to be a helpful strategy for encouraging adherence. Additionally, patients were informed of the risks and benefits of the treatment and learned strategies to improve adherence. These educational points were placed in doctors’ offices to reinforce these messages. Colleagues held weekly meetings to discuss data and feedback as a means to continue long-term momentum.

Blood samples were taken from 20 patients already receiving oral MTX in October 2016 and 21 patients in June 2019. Samples were tested for MTX levels and patients were asked about their MTX usage (day and dose). Reasons for non-adherence included forgetting and stopping treatment due to illness. Physicians were able to use this information to support adherence by teaching patients how to set reminders on their phones and assuring them that they did not need to stop treatment unless they were prescribed antibiotics.

The interventions continued to focus on MI training, consistent information delivery, and messaging, as well as the deployment of a summary bookmark. Between June and August 2016, self-reported non-adherence to MTX was 24.7%. After the introduction of the new methods, between April 2018 and August 2019, non-adherence rates dropped to an average of 7.4%. Reinforcing the key areas (benefits, alcohol guidance, and importance of adhering to the medication) improved from 64% (September 2016) to 94% (January 2018). Non-adherence measured via the biochemical assay was reduced from 56% (September 2016) to only 17% (June 2019). Remission rates improved from 13% in 2014/15 to 37% in 2017/18, which resulted in saving £30,000 per year. This number was estimated by comparing the actual new biologic starters with the expected numbers.

The biggest limitation was the lack of a prescribing database before investigators introduced intervention techniques, as they could not accurately correlate improved adherence with increased persistence on MTX. However, data did show that there had been fewer new patients on biologic drugs than had been expected. Another weakness was that although non-adherence generally means poorer response to treatment, this data can only relate to patients initially starting MTX treatment. As investigators had no prescribing database at the beginning of the study, they could not make similar connections for patients already established on MTX.

Moreover, the study advised patients that they should limit alcohol intake to 6 units per week as liver function may be compromised as a result of MTX treatment and excessive alcohol intake. However, as the population anonymously screened for adherence was not the same at each point, investigators could not say with certainty that this constraint played a role in the decrease. This means that they would not be able to suggest that these recommendations be implemented at other centers moving forward.

Despite the limitations of the study, non-adherence rates were significantly reduced in patients observed throughout the 3 years, indicating that the methods developed and deployed were successful. “The Hawthorne effect of behavior modification as a result of being observed is likely to have played a role in improving adherence rates, and one of the most important culture changes in the department was that clinicians asked about adherence more often,” investigators hypothesized. “We see this as a positive benefit, as the results show that improved adherence correlated with improved remission rates over the same time periods.” They added, “By using a combination of personalized and population-level approaches and maintaining momentum through regular meetings, we were able to demonstrate long-term sustained improvements.“


Barton A, Jani M, Bundy C, et al. Translating research into clinical practice: quality improvement to halve non-adherence to methotrexate. Rheumatology (Oxford). 2021;60(1):125-131. doi:10.1093/rheumatology/keaa214