Research Progress and Clinical Challenges of Precision Targeted Therapy for Autoimmune Diseases

Abstract

The treatment of autoimmune diseases is undergoing a paradigm shift from “broad -spectrum immunosuppression” toward “precision targeted intervention.” Although conventional synthetic disease - modifying antirheumatic drugs (such as methotrexate) remain the cornerstone of therapy, their efficacy ceiling and cumulative toxicity limit long-term use, and clinical practice still has safety gaps, such as inadequate folic acid supplementation. The advent of targeted biologic agents (e.g., TNF -α inhibitors, IL-6R antagonists) and JAK inhibitors has enabled precise blockade of specific inflammatory pathways. However, studies such as ORAL Surveillance have revealed a “safety paradox” of JAK inhibitors regarding cardiovascular and thrombotic risks, highlighting the need for a careful balance between efficacy and risk in clinical practice. To address the clinical challenge of secondary loss of response, precision -switching strategies grounded in immunogenicity theory and therapeutic drug monitoring —including same-target cycling and cross -pathway switching—have emerged as core approaches to optimize efficacy. Meanwhile, bispecific antibodies and CAR-T cell therapies have demonstrated potential breakthrough value in refractory autoimmune diseases; however, their long -term safety, suitability for specific patient populations, and accessibility require further validation through larger-scale clinical studies.