Medication Dosages Predict Successful Control of Difficult-to-Treat RA

senior, elderly man taking prescription medication
To explore predictive prognosis indicators, researchers studied factors of patients with RA who have received successful treatment with DMARDs.

Patients with difficult-to-treat rheumatoid arthritis (RA) are more likely to have successful disease control with treatment with a higher dosage of methotrexate (MTX) without glucocorticoids (GCs), according to study results published in Rheumatology International.

Researchers from Japan analyzed data from patients with RA during a 10-year retrospective study from August 2010 to December 2020. Patients who underwent 1 year of treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) were divided into 2 groups, including patients with difficult-to-treat RA and patients with nondifficult-to-treat RA who achieved disease remission or maintained low levels of disease activity with continued medication use, according to the European Alliance of Associations for Rheumatology (EULAR) definition.

The EULAR criteria needed to attain the diagnosis of difficult-to-treat RA were treatment failure of 2 or more different types of b/tsDMARDs, disease signs and symptoms of at least moderate severity, and problematic management of disease symptoms as perceived by the treating rheumatologist and/or the patient.

A total of 330 patients with RA (71 with difficult-to-treat RA and 259 with nondifficult-to-treat RA) were included in the study. The researchers divided the difficult-to-treat RA group into “success” (n=22) and “failure” groups (n=49) following another year of treatment. Of the 25 patients receiving treatment with GCs and 8.6mg/week or lesser of MTX, 1 patient was categorized into the success group compared with 24 patients in the failure group. Of the 19 patients receiving treatment with at least 8.7mg/week of MTX without GCs, RA was controlled in 12 patients (P <.01).

Researchers assessed disease control using 28-joint disease activity scores (DAS28) at the 3-, 6-, and 12-month follow-ups. The success vs failure group demonstrated significantly lower DAS28 scores, reaching 1.90 or lesser by 3 months and 2.54 or lesser by 6 months. A total of 20 of the 40 patients who achieved these DAS28 scores were categorized into the success group, while only 1 of 6 patients who did not reach these scores achieved “success.”

When selectively analyzing patients who received at least 8.7mg/week of MTX without GCs, 1 patient of the 19 patients were not able to achieve the DAS28 conditions, while 12 of the remaining 18 patients (66.7%) who met the DAS28 conditions were able to achieve disease control.

The researchers concluded, “[Difficult-to-treat] RA is a very difficult situation…however, there is a hint to escape…. GC administration should be avoided, and MTX should be administrated with appropriate dose that may be more than 8.6mg/week.”


Yoshii I, Sawada N, Chijiwa T. Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumatoid arthritis. Rheumatol Int. Published online April 11, 2022. doi:10.1007/s00296-022-05124-1