Younger Age and Erosions Predict “Multi-Refractoriness” to Biologic Agents in RA Patients

This study aimed to describe the characteristics of rheumatoid arthritis (RA) patients who fail to respond to biologics.

Younger age, the presence of erosions, and lack of clinical response to initial biologic disease-modifying antirheumatic drugs (bDMARD) were independent predictors of multirefractoriness to consecutive biologic agents in patients with rheumatoid arthritis (RA), according to a study in Arthritis Research & Therapy.

The study included 402 patients with RA, taken from a cohort in the La Paz University Hospital RA Registry (RA-Paz), who had started a bDMARD between 2000 and 2019. A total of 41 (10%) patients in the cohort experienced an insufficient response to ≥ 3 bDMARDs or 2 bDMARDs with different mechanism of action and were considered multirefractory. Investigators classified patients as having a nonrefractory status if they achieved low disease activity or remission, assessed by DAS-28, with their first bDMARD and maintained this for ≥ 5 years (n=71).

Patients who were multirefractory had a shorter duration of disease between RA diagnosis and starting a bDMARD (6.9 vs 10.0 years; P =.04) and a higher number of previous cDMARDs (P =.001). In addition, multirefractory patients had more frequent erosions (58.5% vs 25.4%; P =.03) and extra-articular manifestations (29.3% vs 12.7%; P <.001) relative to the nonrefractory group.

During the first 6 months of initial treatment, the proportion of patients who responded to therapy was significantly lower in the multirefractory group (43.9% vs 77.5%; P =.001).

A multivariable analysis found that independent predictors of multirefractoriness to bDMARDs included younger age (odds ratio [OR], 0.95; 95% CI, 0.90-0.99), presence of erosions (OR, 3.26; 95% CI, 1.18-9.00), higher baseline DAS-28 (OR, 2.29; 95% CI, 1.39-3.76), and poorer response to first bDMARD after 6 months (OR, 11.12; 95% CI, 3.34-26.82).

Limitations of this study included the use of a definition for multirefractoriness that is not well established as well as the lack of a separate analysis for other factors that may be associated with worse response to biologics, including fibromyalgia, depression, and chronic pain.

According to the researchers, the predictors identified in this study may “be of great interest to clinical practice to avoid inefficient treatments, which entail significant economic burden and potential adverse effects.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Novella-Navarro M, Plasencia C, Tornero C, et al. Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis. Arthritis Res Ther. Published online December 9, 2020. doi:10.1186/s13075-020-02354-1

This article originally appeared on Rheumatology Advisor