Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis

Abstract

Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰ cytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.

Analysis of patents on anti-rheumatoid arthritis therapies issued in China

“…The JAK/STAT pathways have been implicated in the pathogenesis of inflammatory diseases, such as RA [53]. Tofacitinib, a JAK inhibitor, is the first oral non-biologic DMARD approved by the US FDA [54] in 2012. There are only two patents claiming JAK inhibitors in our search results.…”

Current and future pharmacotherapy for alopecia areata

“…It is FDA approved for treatment of rheumatoid arthritis and is undergoing clinical trials both as an oral and a topical treatment for plaque psoriasis [108,109] (NCT02193815, NCT01831466). In rheumatoid arthritis, it is administered orally, in doses of 5 --10 mg twice daily, without regards to meals, with peak plasma concentration 0.5 --1 h postadministration with a bioavailability of 74% [110]. In a study of 59 patients with psoriasis, doses up to 50 mg twice daily proved to be successful and safe [111].…”

Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan

“…As tofacitinib has a different mode of action to biologic agents 46 , such as adalimumab, SAEs were included in the base-case of the model to allow for differences in SAE rates between drug classes. The majority of SAEs observed in patients with RA treated with DMARDs consist of serious infections 47 ; thus, SAEs were defined here as a severe infection (such as meningitis, encephalitis, pneumonia, hepatitis, septicemia, bacteremia, etc.)…”