Response to Second Biologic DMARD Modest After Failure of First Non-TNFi Biologic DMARD

A novel study addresses the important clinical question of how bMDARDs perform after failure of a non-TNFi as first bDMARD in patients with RA.

Patients with rheumatoid arthritis who failed treatment with a non-tumor necrosis factor inhibitor (non-TNFi) biologic disease-modifying antirheumatic drug (bDMARD) showed a modest response to a second bDMARD, according to research findings published in The Journal of Rheumatology.

In general, TNFi agents are the first bDMARDs used when conventional DMARDs (csDMARDs) are not effective, although some patients start with a non-TNFi. In the case of the latter, little guidance exists for choosing a second bDMARD if the non-TNFi treatment fails.

This study used data from 5 Nordic biologic registers to identify patients 18 year of age or older who had been diagnosed with RA and who had initiated their first bDMARD treatment with a non-TNFi (rituximab, abatacept, or tocilizumab) from January 1, 2010, to December 31, 2018. All patients had 12 months of documented follow-up and had started their second bDMARD (TNFi [infliximab, adalimumab, etanercept, certolizumab pegol, or golimumab] or non-TNFi) within 3 months of discontinuing the first bDMARD (or 6 months for rituximab). Endpoints included remaining on the drug at 6 and 12 months after initiating the second bDMARD. Treatment response, measured as European League Against Rheumatism (EULAR) good response, disease activity score 28 joint count (DAS28) low disease activity, and clinical disease activity index (CDAI) low disease activity, was also measured.

In all, 620 patients were included in the analyses: 193 started a non-TNFi as their second bDMARD (86 abatacept, 40 rituximab, 67 tocilizumab) and 427 started a TNFi. The percentage of patients remaining on the second drug was 69% at 6 months and 56% at 12 months. Researchers found little difference in the type of bDMARD used; however, the use of concomitant conventional DMARDs was found to be statistically associated with drug survival (relative risk 0.81; 95% confidence interval [CI] 0.65-0.95). Treatment response at 6 months was modest. Less than one third of patients were still on their second bDMARD and achieved a CDAI score indicating low disease activity or remission. For patients who received a TNFi as their second bDMARD, the response was slightly higher (40% reached DAS28 low disease activity or remission).

Limitations of the study included the observational study design, selection bias in the choice of the second bDMARD, and possible confounding due to missing data and differences in baseline characteristics between the groups.

“This is the first study addressing the important clinical question of how bMDARDs perform after failure of a non-TNFi as first bDMARD. The survival-on-drug and effectiveness of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first ever bDMARD was modest. Concomitant csDMARDs predicts drug survival of the second bDMARD,” the researchers concluded. “Although treatment outcomes in this sub-population of RA are modest, they are not negligible, and some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Dhatzidionysiou K, Hetland ML, Frisell T, et al. Effectiveness of a second biologic after failure of a non-tumor necrosis factor inhibitor as first biologic in rheumatoid arthritis. J Rheumatol. Published online March 1, 2021. doi:10.3899/jrheum.201467