Examining Methotrexate Prescribing Patterns in Early Rheumatoid Arthritis

Disease Detective: Diagnosing Rheumatic Disorders
Disease Detective: Diagnosing Rheumatic Disorders
Findings support the use of subcutaneous methotrexate (MTX) monotherapy or MTX combination as initial MTX-based therapy in patients with early rheumatoid arthritis.

Findings from a recent study published in Arthritis Care and Research showed that while real-world prescribing patterns for methotrexate (MTX)-based therapies vary greatly, use of subcutaneous MTX monotherapy or MTX combination as initial therapy is supported in patients with early rheumatoid arthritis (RA).

Because this “considerable variability” exists, researchers sought to assess real-world patterns of treatment initiation and adjustment for both MTX- and non-MTX-based treatments in patients with early RA. Data were collected from patients diagnosed with early RA enrolled in the Canadian Early Arthritis Cohort (CATCH) Study, a multisite, longitudinal, observational cohort, between January 2007 and March 2017.

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The primary study outcome was a change in both initial and subsequent treatment strategies, including change of route of administration for MTX monotherapy, adding or stopping a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), and/or biologic DMARD, and change in dose or frequency of a csDMARD or biologic DMARD due to treatment inefficiencies or a serious adverse event.

Over 1000 individuals (n=1484) were included in the initial analysis. In general, patients were followed for a median of 37.4 months (interquartile range [IQR] 51 months) and patients who changed their initial treatment were followed for 47.5 months (IQR 49.6 months).

Most patients (92%) began treatment on either oral or subcutaneous MTX monotherapy or MTX plus a csDMARD. Those who were taking MTX triple therapy were younger than the other patient groups (mean age 51.4±13.9 years), and those who were taking oral MTX monotherapy experienced the shortest symptom duration and received the lowest MTX dose compared with other groups.

In patients who began MTX therapy, 61.4% changed the initial therapy, while the remaining patients continued their initial therapy through follow-up. Therapeutic changes were most common in patients who began on oral MTX monotherapy, compared with other MTX-based treatments. This difference was particularly pronounced when compared with those on subcutaneous MTX monotherapy. Only 45% of this group changed their treatment plan vs 79% of patients who started with oral MTX. Fifty-eight percent of patients who initiated MTX double therapy and 66% of patients who initiated MTX triple therapy changed their treatment regimen.

Investigators noted that most adjustments of therapy involved either adding a DMARD to the treatment regimen or changing to a non-MTX DMARD. Patients being treated with biologics and triple therapy experienced a longer time without a change in treatment (hazard ratio [HR], 0.26; 95% CI, 0.16-0.42 and HR, 0.57; 95% CI, 0.38-0.85).

Side effects occurred at a similar rate among those on MTX monotherapy (18% to 26%) and were higher among those on MTX triple therapy (50%). After transitioning to a subsequent therapy, 10% of patients stopped their current treatment regimen due to loss of efficacy or a serious adverse event. Side effect frequency was higher among those on MTX double or triple therapy vs MTX monotherapy, biologics, or non-MTX csDMARDs (33% or 38% vs between 19% to 22%, respectively).

Study limitations included potential unidentified confounders and physician and patient preferences not being captured by the study model.

“The present study showed large variability in the way MTX-based therapies are prescribed in routine care [and] practice,” the researchers of the study concluded. These findings “support initial subcutaneous MTX-based or MTX-combined therapy, and either biologic addition or triple therapy in [patients with RA] who fail initial MTX monotherapy.”

The CATCH Study was financially supported via unrestricted research grants from Amgen, Pfizer Canada, UCB Canada, AbbVie, Bristol-Myers Squibb, Medexus Inc., Eli Lilly Canada, Merck Canada, and Sandoz Canada Pharmaceuticals, as well as previous support from Hoffmann-LaRoche, Janssen Biotech, and Sanofi Genzyme.


Moura CS, Schieir O, Valois MF, 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