Long-term persistence of biological agents in the treatment of patients with rheumatoid arthritis: a systematic literature review and meta-analysis.

INTRODUCTION

Treatment persistence is a surrogate marker for long-term treatment success.

OBJECTIVES

To assess the persistence of biological agents used for treatment of patients with rheumatoid arthritis (RA) over 5 years period and determine variables associated with persistence or discontinuation.

METHODS

A systematic literature review (SLR) and meta-analysis were performed. We performed a bibliographic search through Pubmed, Cochrane and Lilacs databases, and ACR, EULAR, PANLAR abstracts until January 2020. Two independent reviewers evaluated the identified publications, by title and abstract and full text, according to PICO methodology.

ELIGIBILITY CRITERIA: RA patients ≥ 18 years, treated with biological agents, which measured persistence/ discontinuation for a period of time ≥ 5 years and who were in English or Spanish language.

RESULTS

Among 809 articles, 56 articles were selected, leading to a total of 72,677 (range: 79-10,396) patients, with a mean age of 53.8 years ± 12.1, 78.2% female and an average RA disease duration of 9.7 years ± 8.4. Data from 29 publications were pooled for an exploratory meta-analysis of the persistence of b-DMARDs in the 2nd line of treatment at 5 years. Tocilizumab (TCZ) had the highest persistence 66% (CI 95% 60-72), followed by golimumab (GLM) 62% (47-75). Regarding the 3rd therapeutic line, the greater persistence corresponded to abatacept (ABA) 45% (41-50) and etanercept (ETN) 41% (30-53). Lower survival rates predictors were: greater use of steroids, higher baseline disease activity, and female gender.

CONCLUSIONS

In this study, TCZ and GLM showed higher 5-years persistence vs other b-DMARDs in 2nd line treatment. Key Points • The persistence of biologic disease modifying anti-rheumatic drugs (b-DMARDs) is a surrogate marker of long-term treatment success as it represents an indirect measure of clinical effectiveness, the absence of significant adverse events (AE) and satisfaction with treatment. • This systematic literature review (SLR) and meta-analysis included observational studies and long-term extension of randomized controlled studies, allowing us to evaluate drug retention over a 5-year period, from different perspectives and the b-DMARDs that have been on the market for less time. • The highest 5-year persistence of b-DMARDs in patients with inadequate response to conventional synthetic (cs-) DMARDs was for tocilizumab and golimumab. While in b-DMARDs experienced patients, abatacept and etanercept presented the higher retention.