Topical 2% tofacitinib for children with alopecia areata, alopecia totalis, and alopecia universalis

Putterman, Elana; Castelo‐Soccio, Leslie

doi:10.1016/j.jaad.2018.02.031

Cited by 51 publications

(38 citation statements)

References 4 publications

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“…There were some studies with overlapping populations that were removed . After detailed evaluation of these articles, a total of 30 articles were included in the present study, comprising four cohort studies (comprising 221 patients) and 26 case reports/case series/trials with individual patient level data (comprising 92 patients).…”

Section: Resultsmentioning

confidence: 99%

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

Phan

Sebaratnam

2019

Acad Dermatol Venereol

157

150

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There have been a number of case reports and small clinical trials reporting promising outcomes of Janus Kinase (JAK) inhibitors tofacitinib, ruxolitinib and baricitinib for alopecia areata (AA). The majority of the literature to date is based on small volume data, with a lack of definitive evidence or guidelines. To determine the expected response of AA to JAK inhibitor therapy and factors which influence response and recurrence rates. A systematic review and meta-analysis was performed according to PRISMA guidelines. From 30 studies and 289 cases, there were 72.4% responders, good responders 45.7% and partial responders 21.4%. Mean time to initial hair growth was 2.2 AE 6.7 months, and time to complete hair regrowth was 6.7 AE 2.2 months. All 37 recurrences occurred when treatment was ceased after 2.7 months. Oral route was significantly associated with response to treatment compared to topical therapy. No difference was found between paediatric and adult cases in proportion of responses. There is promising low-quality evidence regarding the effectiveness of JAK inhibitors in AA. Future large-sized randomized studies are required to confirm findings.

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Section: Resultsmentioning

confidence: 99%

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

Phan

Sebaratnam

2019

Acad Dermatol Venereol

157

150

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“…Interestingly, tofacinib has been successfully applied in different autoimmune disorders (303, 304). Moreover, a topical preparation of tofacinib was shown to be effective in alopecia areata (305). Based on these findings, it would be intriguing to evaluate the potential benefit of topical JAK inhibitors as a local adjuvant therapy in pemphigus.…”

Section: Emerging Therapiesmentioning

confidence: 99%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

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“…61 There were variable responses reported with tofacitinib 2% in a liposomal base in 11 pediatric patients with most having a cosmetically acceptable response, defined as sufficient growth to cover the residual areas of loss; there were 2 individuals with no response and 1 with worsening of disease. 70 The authors suggest that this product could be considered as adjunctive treatment or as second-line therapy in the pediatric population. 70 A recently published open-label, single-centre, pilot study with 2% tofacitinib ointment BID reported only 3 out of 10 responders with a mean SALT improvement of 34.6%, but 7 participants had no response after 24 weeks.…”

Section: Case Discussionmentioning

confidence: 99%

The Use of Janus Kinase Inhibitors in Alopecia Areata: A Review of the Literature

et al. 2019

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Alopecia areata (AA) is a chronic, immune-mediated disorder that targets hair follicle epithelium, thereby restricting hair growth in localized patches. Although several therapies for AA have been tested, responses with traditional therapies have been limited. In recent years, numerous reports have been published of patients with AA responding to Janus kinase (JAK) inhibitors. This literature review aims to describe AA pathophysiology, explore how and why JAK inhibitors can be used for AA treatment, and review published case reports, case series, and open-label studies published to date. Pathogenesis of AA includes interactions between genetic, environmental, and immune factors and is mediated by the cytokines interferon-γ and interleukin (IL)-15. JAK inhibition resulting in hair regrowth in some cases supports that AA is associated with the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. The emergence of JAK inhibitors for AA therapy is changing the way health care providers think about and treat AA. A mixture of animal model studies and human case studies have reported the use of baricitinib (JAK 1/2), ruxolitinib (JAK 1/2), and tofacitinib (JAK 1/3) for the management of AA. JAK inhibition has shown potential as an effective AA therapy when used in case studies, case series, and open-label trials. Formal clinical trials are ongoing and will yield more definitive conclusions about the safety and efficacy of JAK inhibitors.

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Topical 2% tofacitinib for children with alopecia areata, alopecia totalis, and alopecia universalis

Cited by 51 publications

References 4 publications

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

Pemphigus: Current and Future Therapeutic Strategies

The Use of Janus Kinase Inhibitors in Alopecia Areata: A Review of the Literature

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