Can we cure rheumatoid arthritis?

Rheumatoid arthritis (RA) persists as a chronically progressive autoimmune disorder, notwithstanding significant advancements in early intervention and precision-targeted therapeutics. While treat-to-target paradigms and disease-modifying antirheumatic drugs ameliorate clinical outcomes, sustained drug-free remission (SDFR) or even cure remains elusive, underscoring the need for innovative strategies addressing underlying immunopathogenic mechanisms. Prolonged SDFR implies cure or eradication of disease, but there is no consensus definition of cure because it has rarely been contemplated in RA. Pathogenic immune circuit resilience, stromal hyperactivation, persistent structural abnormalities, and genetic susceptibilities constitute multifactorial barriers to a cure. Emerging therapies — including novel biologics, cellular interventions, and gene editing — aim to reprogram pathogenic immune responses rather than suppress symptoms and may have the potential for both SDFR and possibly cure. Whereas preclinical and early clinical data suggest the potential to modify disease trajectories, durable resetting of the RA immune system toward normal has not yet been conclusively demonstrated or uniformly achieved in RA. The ‘window of opportunity’ paradigm postulates that early-stage immunomodulatory interventions may alter the disease trajectory. However, the optimal therapeutic approaches for capitalizing on this temporal window remain debated, particularly regarding the integration of personalized biomarkers and mechanistic targets.

This review summarizes advancements in RA therapeutics, evaluating whether emerging modalities can pivot the clinical paradigm from symptomatic management to the induction of persistent immunological normalization and cure. Although definitive cure remains on the far horizon, the rapid convergence of precision medicine, next-generation immunotherapy, and translational research underscores a paradigm shift toward curative strategies.