Patients With RA Benefit From Treatment With Biologic and Targeted DMARD Therapy

Researchers investigated treatment responses to sequential lines of biologic or targeted synthetic DMARD therapy in patients with RA to determine if they experienced benefits from a trial-and-error approach to treatment.

Many patients with rheumatoid arthritis (RA) experience treatment benefits following repeated trials with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), according to study results published in Rheumatology (Oxford).

Data derived from the national prospective, observational British Society for Rheumatology Biologics Register for RA between 2001 and 2020 were used in the current analysis to identify change in a new b/tsDMARD (except for biosimilar switches), which was defined as a new line of therapy.

The researchers sought to describe treatment outcomes with each line of b/tsDMARD therapy by comparing treatment outcomes, including disease activity score in 28 joints (DAS28) remission (≤2.6), low disease activity (LDA; ≤3.2) at 6 months, and median time to discontinuation of the medication.

A total of 22,934 participants (76% women; mean age, 56 years) who were initiating a first b/tsDMARD were included in the current study. Of these participants, 10,823, 5056, 2128, 767, and 292 initiated second-, third-, fourth-, fifth-, and sixth-line therapy, respectively. The majority of the participants (71%) had sufficient data available for DAS28-derived outcome analyses.

Although tumor necrosis factor (TNF) inhibitors were the most frequently used first-line agent (94%) and second-line agent (60%), the selection of subsequent-line agents changed over time. Rituximab was the most common third-line treatment (39%), interleukin (IL)-6 inhibitors were the most commonly used fourth-line agents (33%), abatacept was the most often used fifth-line agent (32%), and Janus kinase (JAK) inhibitors were the most commonly used sixth-line agents (28%).

Overall, 17%, 13%, and 8% to 13% of participants attained DAS28 remission following first-, second-, and third- through sixth-line therapy, respectively.

Researchers noted that LDA was attained in 29%, 23%, and 17% to 22% of patients after first-, second-, and third- through sixth-line therapy, respectively. Study participants remained on first-line therapy for a median of 2.6 years, which ranged from 1.0 years to 1.4 years for the second to the sixth lines of therapy.

Overall, although treatment responses to subsequent lines of b/tsDMARDs were decreased when compared with those observed with first-line b/tsDMARD at a cohort level, good responses were recorded across all lines of therapy and were similar across the third to the sixth lines of therapy.

One of the study limitations included the fact that the prescribing practice was confined to national guidelines, which may have prevented generalizability to other health care systems. In addition, the researchers did not evaluate treatment response stratified by reason of previous treatment discontinuation, in part, due to the limited sample size in later lines of therapy and missing data.

The researchers concluded, “Further research to improve treatment selection are needed to prevent prolonged trial and error approaches in some patients.”

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


Zhao SS, Kearlsey-Fleet L, Bosworth A, Watson K, Hyrich KL; BSRBR-RA Contributors Group. Effectiveness of sequential biologic and targeted disease modifying anti-rheumatic drugs for rheumatoid arthritis. Rheumatology (Oxford). Published online March 31, 2022. doi:10.1093/rheumatology/keac190