# Efficacy and Safety of Biologic and Targeted Synthetic DMARDs in Young-Onset Rheumatoid Arthritis: A Systematic Review

## TL;DR

This paper reviews how well biologic and targeted drugs work in young-onset rheumatoid arthritis, finding better outcomes in younger patients compared to older ones.

## Contribution

The study provides a systematic review of b/tsDMARDs in young-onset rheumatoid arthritis, highlighting superior clinical outcomes and safety profiles in younger patients.

## Key findings

- Younger patients showed higher remission rates and greater reductions in disease activity compared to older-onset rheumatoid arthritis patients.
- Tumor necrosis factor inhibitors, interleukin-6 antagonists, and Janus kinase inhibitors demonstrated consistent clinical efficacy in younger populations.
- Safety profiles were favorable with no age-specific safety signals identified, though infections and lab abnormalities were common.

## Abstract

Background: Young-onset rheumatoid arthritis (YORA), defined by disease onset between 16–40 years, raises distinct clinical challenges related to long-term disease burden, fertility, and prolonged exposure to immunomodulatory therapy. Despite its relevance, evidence regarding treatment outcomes in this population remains limited and heterogeneous, largely due to inconsistent definitions of YORA across studies. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines to synthesize contemporary evidence on the efficacy and safety of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in younger rheumatoid arthritis populations. A structured search of PubMed and Embase was performed to identify studies published between 2020 and 2025 that evaluated advanced therapies in patients with young-onset rheumatoid arthritis or in rheumatoid arthritis cohorts reporting age-stratified outcomes for younger adults. Results: From the screened literature, 16 studies met the predefined inclusion criteria, including 6 studies explicitly defining YORA based on age at disease onset and 10 studies reporting outcomes in younger adult subgroups (<40–45 years). Across studies, younger patients demonstrated higher remission rates, greater reductions in disease activity, and superior treatment persistence compared with older-onset rheumatoid arthritis cohorts. Tumor necrosis factor inhibitors, interleukin-6 receptor antagonists, and Janus kinase inhibitors showed consistent clinical efficacy. Structural outcomes, reported in a limited number of studies, suggested low rates of radiographic progression in younger patients. Safety profiles were generally favorable, with infections and laboratory abnormalities representing the most reported adverse events and no age-specific safety signals being identified. Conclusions: Biologic and targeted therapies provide substantial clinical benefit in YORA and younger adult RA populations, with outcomes being generally superior to those observed in older-onset RA. However, heterogeneity in YORA definitions and limited long-term data highlight the need for prospective, age-at-onset-defined studies and extended pharmacovigilance to better inform lifelong treatment strategies.