Researchers at the Medical University of Vienna developed a new "therapeutic matchmaking" framework for rheumatoid arthritis management, prioritizing safety profiles and patient characteristics over traditional efficacy measures, according to a new review.

In the study, in Nature Reviews Rheumatology, the researchers reported that biological therapies show comparable efficacy rates, with ACR20, ACR50, and ACR70 response rates of approximately 60%, 40%, and 20%, respectively, in methotrexate-insufficient responders. Given this similarity, the framework suggested that treatment selection should increasingly consider safety and multimorbidity rather than efficacy alone.

Key safety considerations identified included:

• Tumor necrosis factor (TNF) inhibitors: Contraindicated in moderate-to-severe heart failure (NYHA class III/IV).
• Janus kinase (JAK) inhibitors: Require caution in patients with atherosclerotic cardiovascular disease or venous thromboembolism because of the associated risks.
• Interleukin (IL)-6 inhibitors: Linked with increased risk of gastrointestinal perforation, particularly with a history of diverticulitis.
• Rituximab: Requires careful use in patients with hypogammaglobulinemia.
• Abatacept and JAK inhibitors: Caution advised in patients with recent malignancies.

Three trials (ARCTIC, TaSER, IMAGINE-RA) examined whether subclinical imaging targets offered an advantage. Results showed no statistically significant difference in primary outcomes between strategies focusing on subclinical versus clinical outcomes.

The study’s "dissociation concept" highlighted that low disease activity states can halt structural progression when treated with biological disease-modifying antirheumatic drugs (DMARDs) or JAK inhibitors, an effect not seen with conventional DMARDs. This effect was documented for:

• TNF inhibitors
• IL-6 inhibitors
• Rituximab
• JAK inhibitors.

Additionally, patients with rheumatoid arthritis often present with significant multimorbidity, necessitating efficient strategies given the worldwide shortage of rheumatologists.

The framework addressed three primary patient scenarios:

• Early disease with good tolerability
• Difficult-to-treat or refractory disease
• Patients with significant comorbidities.

While traditional treat-to-target approaches aim for disease activity thresholds, the new "smart-to-target" approach proposed a balance between therapeutic effort and clinical benefit, noting that achieving subclinical remission may require a disproportionate increase in effort relative to clinical remission.

A statement of ethics declarations can be found in the study.