Switching From TNFi to Non-TNFi Linked With Sustained Clinical Response in Patients With RA

Study investigators saw sustained clinical response regardless of whether the participant with rheumatoid arthritis (RA) had discontinued the first tumor necrosis factor inhibitor (TNFi) due to a primary or secondary inefficacy.

Patients with rheumatoid arthritis (RA) who discontinued a first tumor necrosis factor inhibitor (TNF) and switched to a non-TNFi were 3 times more likely to attain a sustained clinical response, a study published in Therapeutic Advances in Musculoskeletal Disease found.

The study authors said the same result occurred regardless of whether the participant had discontinued the first biologic due to a primary or secondary inefficacy.

Biological therapy has dramatically improved the prognoses of patients with RA. TNFis have regularly been used as first-line biological agents—specifically, biological disease-modifying antirheumatic drugs (bDMARDs)—to help stop inflammation and are globally used to treat various inflammatory conditions. However, 30% to 40% of patients have an inadequate response to a TNFi due to inefficacy or intolerance.

This prospective observational study included 127 adult patients with RA who discontinued their first TNFi between January 1999 and March 2016 and were subsequently treated with a second bDMARD, which was available after 2010. Rituximab (RTX), abatacept (ABA), and tocilizumab (TCZ) were the non-TNFi bDMARDs included in this study.

“Because not all biologics included in the study were available before 2010, we have performed a subanalysis comparing the populations that started the second bDMARDs before and after this period to avoid calendar time bias,” the authors clarified.

The goals of the study were to compare long-term efficacy of TNFis against non-TNFis after discontinuing a previous TNFi and to identify potential risk factors affecting long-term clinical response to a second bDMARD among patients with RA. The researchers also wanted to assess if reason for discontinuation of the first biologic drug influences the response to the second biologic.

Researchers measured disease activity at baseline and at 6, 12, and 24 months after switching from a TNFi to a non-TNFi. Primary outcome was the proportion of participants achieving good or moderate EULAR response.

Of 127 participants with RA, 77 (61%) received a second TNFi and 50 (39%) switched to a non-TNFi. The median age for TNFi users was 55 years and for non-TNFi users was 57 years.

No differences were observed between groups at the 6-month and 12-month follow-ups, but a significant difference was noted at the 24-month follow-up. Here, the proportion of patients with a good or moderate EULAR response was higher in the non-TNFi group (77%) compared with the TNFi group (49%). Regression models showed that changing to a non-TNFi was significantly associated with EULAR response at 24 months.

“The results of this study support the findings of most of the studies that have evaluated the efficacy of a second biological agent,” the authors said. “The only head-to-head comparison of these randomized therapies published to date demonstrated greater response rates with RTX, ABA, and TCZ compared with TNFi.”

The stronger EULAR response after switching to a drug with another mechanism of action compared with a second TNFi remained evident regardless of whether the reason for switching was loss or lack of efficacy.

“Future additional analyses validating these results in a larger cohort may be useful to confirm our findings and to better clarify which second bDMARD will benefit patients the most according their individual characteristics,” the authors said.


Bogas P, Plasencia-Rodriguez C, Navarro-Compán V, et al. Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study. Ther Adv Musculoskel Dis. Published online November 24, 2021. doi:10.1177/ 1759720X211060910