Tofacitinib: A Review in Rheumatoid Arthritis

Abstract

Tofacitinib (Xeljanz) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤ 24 months' duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (csDMARD; as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤ 96 months). Tofacitinib monotherapy inhibited progression of structural damage in methotrexate-naïve patients during ≤ 24 months' treatment, with beneficial effects also seen in patients receiving tofacitinib plus methotrexate as second-line therapy for 12 months. Tofacitinib was generally well tolerated during ≤ 114 months' treatment, with most adverse events of mild or moderate severity. The tolerability profile of tofacitinib was generally similar to that of biological DMARDs (bDMARDs), with infections and infestations the most common adverse events (AEs) in tofacitinib recipients. However, the incidence of herpes zoster (HZ) was higher with tofacitinib than in the general RA population, although infections were clinically manageable. When added to background methotrexate, tofacitinib was noninferior to adalimumab in terms of efficacy, and both combination therapies had generally similar tolerability profiles. Although additional comparative studies are needed to more definitively position tofacitinib relative to bDMARDs and other targeted synthetic DMARDs, current evidence indicates that oral tofacitinib is a useful option for the treatment of patients with RA.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…There are a number of JAKi currently both used and under investigation for use in several autoimmune systemic diseases such as RA, PsO, PsA, some of which are also approved or under investigation in other indications [287]. Tofacitinib has specificity for JAK3 and JAK1 over JAK2 and baricitinib mainly inhibits JAK1 and JAK2 [288,289] while upadacitinib that will be soon marketed demonstrated a 74-and 58-fold greater selectivity for JAK1 over JAK2 and JAK3, respectively [290].…”

New therapies in development for the management of non‐infectious uveitis: A review

“…Unlike filgotinib, tofacitinib is less selective in terms of its JAK inhibition and acts on JAK1 and JAK3, and to a lesser extent on JAK2 . Tofacitinib has been approved by the FDA for the treatment of rheumatoid arthritis and ulcerative colitis . One case report described a patient who developed cytomegalovirus retinitis retinitis after administration of methotrexate and tofacitinib for rheumatoid arthritis (RA) .…”

“…217 Tofacitinib has been approved by the FDA for the treatment of rheumatoid arthritis and ulcerative colitis. 218,219 One case report described a patient who developed cytomegalovirus retinitis retinitis after administration of methotrexate and tofacitinib for rheumatoid arthritis (RA). 220 Tofacitinib is currently being evaluated in a clinical trial for uveitis and scleritis (NCT03580343).…”

Development and validation of a rapid and sensitive UPLC–MS/MS assay for the quantification of tofacitinib in human plasma

“…Rheumatoid arthritis (RA) is a complex, chronic autoimmune disease that is characterized by inflammation synovitis, leading to progressive destruction of joints. Synthetic and biological disease‐modifying antirheumatic drugs have been the mainstay of the treatment and management of patients with RA in the early and advanced disease phases (Bannwarth, Kostine, & Poursac, ; Dhillon, ). As RA is a complex disorder with many biological subsets, it is essential to have disease‐modifying antirheumatic drugs with unique modes of action which can supplement the current assemblage of drugs.…”