Topical Tofacitinib Research Articles

Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction.

Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P<0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P<0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P<0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.

Efficacy of topical tofacitinib, a Janus kinase inhibitor, in the treatment of plaque psoriasis.

Efficacy of topical tofacitinib, a Janus kinase inhibitor, in the treatment of plaque psoriasis.

A Review of Tofacitinib in the Treatment of Rheumatoid Arthritis and Psoriasis

Tofacitinib is a novel Janus kinase (JAK) inhibitor. JAKs activate immune cells and pro-inflammatory cytokines. Thus, they are critical in the pathogenesis of many diseases including autoimmune diseases such as rheumatoid arthritis (RA) and psoriasis. Existing treatments for RA and psoriasis do not provide all patients with sufficient disease control. Furthermore, some patients develop resistance or have adverse events to current therapies. Patients whose disease is not controlled appropriately by available treatments highlight the need for drugs with novel targets, convenient administration routes, continued efficacy, and long-term tolerability. Tofacitinib can be administered orally or topically and has been shown to be an effective treatment for RA and psoriasis. This article reviews the mechanism of action, pharmacodynamics, pharmacokinetics, and metabolism of tofacitinib and discusses the clinical trials conducted to show the efficacy and safety of oral tofacitinib in the treatment of RA and oral and topical tofacitinib in the treatment of psoriasis.

Immunomodulatory Effects of Topical Ophthalmic Tofacitinib (Cp-690,550) in Dry Eye Disease

Ocular surface inflammation is thought to play a key role in dry eye pathogenesis and clinical manifestation. Multiple inflammatory cytokines signal through intracellular janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Tofacitinib (CP-690,550), a potent and selective inhibitor of JAKs, has been approved for the treatment of rheumatoid arthritis in the US and is in clinical development for the treatment of other autoimmune diseases. Topical ophthalmic tofacitinib was evaluated and has shown immunomodulatory activity in reducing ocular surface inflammation in dry eye, thus, has the potential to improve ocular surface health in dry eye.

A randomized phase 2a efficacy and safety trial of the topical J anus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis

BackgroundTofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis.ObjectivesThis phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis.MethodsTwo tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle-controlled trial (NCT01246583). Seventy-one patients were randomized 2 : 1 : 2 : 1 to 2% tofacitinib ointment 1, vehicle 1, 2% tofacitinib ointment 2 and vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque with or without one or more nontarget plaques and normal skin.ResultsThe primary endpoint of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) –54·4%] vs. vehicle 1 (LSM –41·5%), but not ointment 2 (LSM –24·2%) vs. vehicle 2 (LSM –17·2%). Secondary endpoints (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment vs. corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application-site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2.ConclusionsTofacitinib ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted.

An evaluation of the effect of topical tofacitinib (CP-690, 550) on pruritus and patient satisfaction with study medication in a phase IIA trial for plaque psoriasis

An evaluation of the effect of topical tofacitinib (CP-690, 550) on pruritus and patient satisfaction with study medication in a phase IIA trial for plaque psoriasis