Department of Research, Sir Ganga Ram Hospital, New Delhi, 110060, India.
Department of Rheumatology and Clinical Immunology, Sir Ganga Ram Hospital, New Delhi, 110060, India.
Mol Cell Biochem. 2023 Jan;478(1):69-88. doi: 10.1007/s11010-022-04492-3. Epub 2022 Jun 21.
Rheumatoid arthritis (RA) is characterised by severe joint and bone damage due to heightened autoimmune response at the articular sites. Worldwide annual incidence and prevalence rate of RA is 3 cases per 10,000 population and 1%, respectively. Several genetic and environmental (microbiota, smoking, infectious agents) factors contribute to its pathogenesis. Although convention treatment strategies, predominantly Disease Modifying Anti Rheumatic Drugs (DMARDs) and Glucocorticoids (GC), are unchanged as the primary line of treatment; novel strategies consisting of biological DMARDs, are being developed and explored. Personalized approaches using biologicals targetspecific pathways associated with disease progression. However, considering the economic burden and side-effects associated with these, there is an unmet need on strategies for early stratification of the inadequate responders with cDMARDs. As RA is a complex disease with a variable remission rate, it is important not only to evaluate the current status of drugs in clinical practice but also those with the potential of personalised therapeutics. Here, we provide comprehensive data on the treatment strategies in RA, including studies exploring various combination strategies in clinical trials. Our systematic analysis of current literature found that conventional DMARDs along with glucocorticoid may be best suited for early RA cases and a combination of conventional and targeted DMARDs could be effective for treating seronegative patients with moderate to high RA activity. Clinical trials with insufficient responders to Methotrexate suggest that adding biologicals may help in such cases. However, certain adverse events associated with the current therapy advocate exploring novel therapeutic approaches such as gene therapy, mesenchymal stem cell therapy in future.
类风湿关节炎（RA）的特征是关节和骨骼严重受损，这是由于关节部位的自身免疫反应加剧所致。全球 RA 的年发病率和患病率分别为每 10000 人 3 例和 1%。几种遗传和环境（微生物群、吸烟、感染因子）因素促成了其发病机制。虽然传统的治疗策略，主要是疾病修饰抗风湿药物（DMARDs）和糖皮质激素（GC），作为一线治疗方法没有改变；但新型策略包括生物 DMARDs，正在被开发和探索。使用生物制剂的个体化方法针对与疾病进展相关的特定途径。然而，考虑到与这些药物相关的经济负担和副作用，对于 cDMARDs 治疗应答不足的患者，需要制定新的分层策略。由于 RA 是一种复杂的疾病，缓解率各不相同，因此不仅要评估目前临床实践中药物的现状，还要评估那些具有个性化治疗潜力的药物。在这里，我们提供了 RA 治疗策略的全面数据，包括探索临床试验中各种联合策略的研究。我们对现有文献的系统分析发现，传统 DMARDs 联合糖皮质激素可能最适合早期 RA 病例，而传统和靶向 DMARDs 的联合可能对治疗血清阴性、中重度 RA 活动度患者有效。对于对甲氨蝶呤无应答的患者，临床试验表明添加生物制剂可能有所帮助。然而，当前治疗方法的某些不良反应促使我们在未来探索新的治疗方法，如基因治疗、间充质干细胞治疗等。
