Recent progress in treatments of rheumatoid arthritis: an overview of developments in biologics and small molecules, and remaining unmet needs

Abstract

Through treatment with biological DMARDs (bDMARDs) or targeted synthetic (tsDMARDs) such as Janus kinase (JAK) inhibitors in addition to MTX, clinical remission has become a realistic therapeutic goal for the majority of patients with RA, and sustained remission facilitates prevention of joint damage and physical dysfunction. Long-term safety and sustained inhibition of structural changes and physical dysfunction by bDMARDs have been reported. The development of next-generation bDMARDs and expansion of their indications to various autoimmune diseases are expected. Five JAK inhibitors show comparable efficacy to bDMARDs, and the latest ones are effective for overcoming difficult-to-treat RA regardless of prior medications. Patients treated with JAK inhibitors should be adequately screened and monitored for infection, cardiovascular disorders, thrombosis, malignancies and so on. Advances in therapeutic strategies, including the differential use of therapeutic drugs and de-escalation of treatment after remission induction, are prioritized.

Keywords: rheumatoid arthritis; DMARD; bDMARD; clinical trial; csDMARD; remission; safety; treatment; tsDMARD.

Fig. 1

Biological DMARDs approved for RA For the treatment of RA there are five TNF-targeting drugs, two IL-6 receptor-targeting drugs, one B-cell antigen CD20-targeting antibody and one selective T-cell costimulatory modulator, each of which are marketed. *ABT-122, a bispecific antibody, is not approved yet.

Fig. 2

Treatment strategies of RA towards drug holiday and ‘cure’ Intensive treatment is required for inducing remission in RA, but subsequently maintaining remission with high adherence and safety is prerequisite for a good long-term outcome. Achievement of sustained remission with a drug holiday/withdrawal regime suggests the possibility of achieving a drug-free remission and even cure in the later stages of treatment. However, the factors or drivers that inhibit the transition from remission to cure may exist not only in the immune system, but also in the mesenchymal, intestinal, nerve and the metabolic systems. bDMARD: biological DMARD; CDAI: Clinical Disease Activity Index; HAQ-DI: HAQ Disability Index; JAK: Janus kinase; SDAI: Simplified Disease Activity Index.