Rheumatoid Arthritis and JAK-STAT Inhibitors: Prospects of Topical Delivery

Abstract

Abstract:Rheumatoid arthritis (RA) is the most common musculoskeletal disease in the world. The clinical prospects have increased tremendously since the advent of biological agents as therapy options. NSAIDs such as indomethacin, celecoxib, and etoricoxib are used often in the treatment of RA but off-target effects decreased their use. DMARDs such as methotrexate and etanercept were also effective in the treatment of RA, but tolerance to methotrexate developed in many cases. Janus kinase inhibitors (JAKi) have also gained popularity as a treatment option for rheumatoid arthritis. Tofacitinib is the foremost JAK inhibitor that is used to treat RA as an individual agent or in combination with other DMARDs. The most frequently used route of administration for JAKi is oral. Since oral formulations of JAK inhibitors have a number of health hazards, such as systemic toxicity and patient noncompliance, topical formulations of JAK inhibitors have emerged as a preferable alternative for administering JAK inhibitors. Tofacitinib delivered topically, seems to have the potential to eliminate or reduce the occurrences of negative effects when compared to tofacitinib taken orally. Given the scarcity of knowledge on the techniques for topical distribution of JAKi, more effort will be required to develop a stable topical formulation of JAKi to address the limitations of oral route. The current review looks at JAK inhibitors and the ways that have been used to generate topical formulations of them.