Dual-targeting macromolecules: Bispecific antibodies as next-generation therapeutics for rheumatoid arthritis

Bispecific antibodies (BsAbs) are an innovative and novel class of biological therapeutic agents for rheumatoid arthritis (RA) that can simultaneously modulate two different immune pathways. Antibody engineering has made significant progress in recent years, enabling the modulation of interactions between inflammatory cascades and cellular processes essential to disease progression through the use of targeted molecules. BsAbs have shown promising efficiency and safety profiles in preclinical studies and early-phase clinical trials; however, they still pose challenges concerning stability, pharmacokinetics, and immunogenicity. Additionally, emerging evidence underscores the importance of refining biomarker approaches to predict treatment response and inform patient selection. Moreover, the intricate interactions between cytokine networks and cellular dynamics require further clarification in the future, as understanding this relationship more effectively can lead to more efficient optimization of these agents. Employing BsAbs facilitates the concurrent targeting of multiple molecular pathways, which may be overlooked by monotherapy approaches. Preliminary research indicates that such simultaneous modulation has the potential to enhance disease management and improve overall patient outcomes. This review article intends to critically discuss the existing preclinical and clinical findings on BsAbs in RA, highlight current research developments, and propose strategic approaches to overcome barriers hindering their translation into clinical practice.