March 06, 2019
4 min read

Patients treated late, women at higher risk for refractory RA

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Manuel Bécède

A delayed initial treatment, as well as female sex and a higher disease activity, are major predictors of refractory rheumatoid arthritis, according to data published in Seminars in Arthritis and Rheumatism.

“Despite the fact that treatment of RA has experienced tremendous innovations over the past 20 years, a subgroup of patients remains to pose a challenge to rheumatologists,” Manuel Bécède, MD, of the Medical University of Vienna, told Healio Rheumatology. “These patients are characterized by a lack of clinical response to numerous consecutive therapeutic interventions and may exhibit significant progression of joint damage and irreversible disability. This group of patients is currently poorly defined and is sometimes referred to as ‘difficult’ or ‘problematic’ RA, or simply as ‘refractory.’”

“Without knowing risk factors for refractory RA, the clinical recognition of a patient’s course as refractory inherently comes too late, and physicians may find themselves recognizing that more aggressive initial treatment strategies would potentially have been beneficial to avert the refractory course of the disease,” Bécède added. “Refractory patients are still underrepresented in clinical trials.”

Delayed initial treatment, as well as female sex and a higher disease activity, are major predictors of refractory RA, according to data.
Source: Adobe

To analyze the predictors of refractory RA, Bécède and colleagues reviewed information from a longitudinal academic clinical database, established more than 15 years ago at the Medical University of Vienna’s rheumatology department. They identified 412 patients for inclusion in their study. Of these patients, 70 met the criteria for refractory RA, which the researchers defined as failing to reach at least low disease activity with three or more disease-modifying antirheumatic drug courses, including one or more biological, during a total of 18 months or more.

Those patients were compared to a control group of 102 participants who did response within the first two treatments — these patients were classified as “treatment amenable.” The remaining 240 patients met neither definition. The researchers completed logistic regression analysis to find risk factors for refractory disease courses. They also used sensitivity analyses regarding various definitions of refractory RA, to help confirm their results.

According to the researchers, 92.9% of the patients with refractory RA were women, compared with 70.6% in the control group (P < .001). In addition, patients with refractory RA were younger at disease onset, with a median age of 44.37 years, compared with 51.14 years in the control group (P=.002). They also demonstrated higher disease activity at first onset compared with controls, with a median Clinical Disease Activity Index (CDAI) of 26.06 among those with refractory RA vs. 15.39 for those who were treatment amenable (P < .001).


Lastly, delays in initial treatment were significantly longer among patients with refractory RA, with a median delay of 3.17 years, compared with 1.45 years in the control group (P =.001). Following multivariable analyses, only treatment delay, female sex and higher CDAI remained as independent predictors of refractory disease course.

“The matrix risk model, which includes the identified risk factors of female gender, treatment delay and disease activity, provides a novel tool for the determination of a risk to become a refractory RA patient, thus informing rheumatologists and patients on the potential necessity of a particularly intensive treatment approach,” Bécède said. “We can also conclude on the conceptual and practical presence of the window of opportunity in RA regarding the ability of rheumatologists to change the course of the disease in patients with RA. Thus, delay of DMARD treatment start is a major risk factor of a subsequent therapeutic failure.” – by Jason Laday

Disclosure: Bécède reports no relevant financial disclosures. Please see the study for all other relevant financial disclosures.