ADVANCEMENTS IN TARGETED THERAPIES FOR RHEUMATOID ARTHRITIS: A COMPARATIVE REVIEW OF CONVENTIONAL AND BIOLOGICAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

Rheumatoid arthritis (RA) is an autoimmune disease that causes progressive joint damage and systemic complications, leading to significant physical and socioeconomic impacts. Conventional treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) often fail to halt disease progression and prevent cartilage erosion. The review compares conventional therapies with emerging biological DMARDs (bDMARDs) and explores novel therapeutic targets. The advent of bDMARDs in targeting key inflammatory cytokines, such as Janus kinase (JAK), Tumour Necrosis Factor-alpha (TNF-α), and Bruton’s Tyrosine Kinase (BTK), have significantly improved clinical outcomes. Promising agents such as JAK inhibitors (Tofacitinib, Baricitinib), TNF-α blockers (Adalimumab, Etanercept), and BTK inhibitors are under clinical trials, highlighting the potential of targeted therapies in immune modulation. Most of the compounds possess a heterocycle, especially pyridine scaffold, emphasizing the importance of heterocycle to potentiate drug-receptor interaction. Additionally, this paper mentions the rise of innovative therapies, such as Mesenchymal Stem Cell (MSC) therapy, the DEN-181 immune modulation vaccine, and vagus nerve stimulation devices, which focus on tissue regeneration and novel immune pathways. The explored scaffolds, structure-activity relationships, and pharmacological evaluation of small molecule inhibitors and biologics will provide insights for the design of new chemical entities for potential and plausible RA targets. This comprehensive review emphasizes the paradigm shift towards precision medicine, offering a roadmap for integrating combination therapies and novel immunomodulatory approaches for holistic RA management.