4 Questions About Methotrexate-Based Treatment Strategies in Early RA

Methotrexate (MTX) has remained an integral part of the management of rheumatoid arthritis (RA) and other rheumatic conditions over time, despite numerous therapeutic advances. Still, studies that describe real-world practice patterns on initiation and duration of initial MTX-based treatment strategies, along with subsequent treatment changes, are limited.

A study by Sasha Bernatsky, MD, PhD, and colleagues investigated real‐world practice patterns on MTX–based and non-MTX–based treatment strategies over time in early RA. The findings supported the use of subcutaneous MTX monotherapy or MTX combination therapy as initial therapy in early RA.

Rheumatology Consultant caught up with Dr Bernatsky, who is a James McGill professor within the Faculty of Medicine in the Department of Medicine at McGill University in Montreal, Quebec, Canada. We asked about her research and why MTX is still useful in the management of RA.

Rheumatology Consultant: What prompted you to conduct your study?

Sasha Bernatsky: RA is a serious inflammatory arthritis that affects millions of North Americans. Years ago, many patients lived with untreated disease, causing widespread joint damage and disability. Since the discovery of MTX’s benefits, we can now provide aggressive treatment. Along with early diagnosis, intervention, and tight monitoring of disease activity, we are able to prevent joint damage and disability in many patients. Despite the introduction of new medications over time, MTX is still the anchor drug in RA, and should be part of the first treatment strategy for RA, either as monotherapy or in combination with other medications. The objective of our study was to describe different approaches to initial and subsequent MTX–based treatments, as well as reasons for changing therapy, among a large pan-Canadian cohort of individuals with early RA. Studies like ours better reflect how patients are treated in real life and are a valuable addition to evidence generated by randomized trials. This type of study is important for health care decision-makers, including drug regulators within Health Canada and regional health authorities.

RHEUM CON: Your study found great variability of treatment at initiation and during medication adjustment. Were you surprised by the findings? 

SB: Yes and no. As rheumatologists, we are all aware that there are multiple decision points, and that these decisions are all influenced by different viewpoints of the physician, patient preferences, local management guidelines, and differences in the standard of medical practices in medication coverage. This study was the first to quantify these differences. Interestingly, different physicians seem to have a strong preference for initial therapy with either MTX subcutaneous or MTX in combination with another medication. Physicians’ decisions are also influenced by the rules of provincial formularies. In Ontario, Canada, patients are often required to have failed therapy with MTX and leflunomide, as well as at least one combination of triple therapy with MTX, hydroxychloroquine, and sulfasalazine before being prescribed other medications.

RHEUM CON: In the study, why do you think the individuals who received treatment with biologic medications and with triple therapy went longer without a treatment change? 

SB: There are several hypotheses. One is that these approaches offer more effective, well tolerated strategies. Still, since this was an observational study, the results could be due to confounding factors. For example, physicians may be more likely to start certain treatment strategies among individuals who have a more favorable profile and who would tend to do well. I do believe our results reflect the fact that aggressive treatment affords the best approach for RA patients.

RHEUM CON: What are the next steps of your research?

SB: The Canadian Early Arthritis Cohort (CATCH), led by Dr Vivian Bykerk, is an invaluable resource and I hope to continue collaborations with this great group of researchers. Every year there are more medication options for RA management, so I think it will be important to continue to collect data and repeat some of these analyses in time to see whether results have changed. Also, as time goes on and we have more data, we can delve more into potential interactions with covariates such as sex and age, which might play important roles in patient and physician decisions. In addition, studying patient preferences is key to understanding outcomes in RA. I hope we can one day start pragmatic trials to sort out which treatments are the best for individuals with RA.

Reference:

Moura CS, Schieir O, Valois M-F, et al; Canadian Early Arthritis Cohort (CATCH) Investigators. Treatment strategies in early rheumatoid arthritis methotrexate management: results from a prospective cohort [published online May 21, 2019]. Arthritis Care Res (Hoboken). doi:10.1002/acr.23927.