scholarly journals Acne exacerbation after tofacitinib treatment for alopecia areata

2021 ◽  
Author(s):  
Sawsan Alharthi ◽  
Mohammed Turkmani ◽  
Mohammed Al Jasser
Keyword(s):  
Adverse Effect ◽  
Side Effects ◽  
Alopecia Areata ◽  
Treatment Initiation ◽  
Janus Kinase ◽  
The Novel ◽  
Jak Inhibitors ◽  
History Of ◽  
Facial Acne ◽  
Novel Therapeutic

The major discovery of the novel therapeutic Janus kinase (JAK) inhibitors has been implicated in several dermatological diseases. Recently, studies have shown the efficacy and encouraging results of oral JAK inhibitors as a treatment for alopecia areata (AA). Due to the novelty of this treatment, potential side effects are not fully explored. In this paper, we present a case of a 28-year-old male with a 10-year history of alopecia totalis (AT) treated successfully with tofacitinib with encouraging effects on hair regrowth; however, a significant worsening of the patient’s facial acne was observed four months after AT treatment initiation. JAK inhibitors have promising results in the management of different dermatological conditions including moderate-severe forms of AA with few reported adverse events. Acne exacerbation is a unique observed adverse effect of this therapy. More thorough larger sized studies are needed to further characterize the association between acne exacerbation and the use of JAK inhibitors.

scholarly journals Topical Tofacitinib: A Janus Kinase Inhibitor for the Treatment of Vitiligo in an Adolescent Patient

2021 ◽  
pp. 190-194
Author(s):  
Sineida Berbert Ferreira ◽  
Rachel Berbert Ferreira ◽  
Afonso Cesar Neves Neto ◽  
Silvana Martins Caparroz Assef ◽  
Morton Scheinberg
Keyword(s):  
Case Report ◽  
Skin Disease ◽  
Kinase Inhibitor ◽  
Effective Therapy ◽  
Janus Kinase ◽  
Jak Inhibitor ◽  
Adolescent Patient ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitor ◽  
History Of

Vitiligo is an autoimmune skin disease presenting with areas of depigmentation. Recent reports suggest that Janus kinase (JAK) inhibitors may be an effective therapy. In this case report, we show our experience with an adolescent patient with a long history of generalized and refractory vitiligo, for which treatment with topical tofacitinib, a JAK inhibitor, associated with phototherapy for 9 months, resulted in near complete repigmentation.

A Case of Topical Ruxolitinib Treatment Failure in Alopecia Areata

2017 ◽  
Vol 21 (6) ◽  
pp. 562-563 ◽  
Author(s):  
Maya Deeb ◽  
Renée A. Beach
Keyword(s):  
Alopecia Areata ◽  
Janus Kinase ◽  
Local Administration ◽  
Jak Inhibitors ◽  
Management Options ◽  
Current Management ◽  
Extensive Disease ◽  
Extrinsic Factors ◽  
Intrinsic Factors ◽  
Attractive Option

Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option. Yet, a paucity of data exists on topical JAK inhibition in AA. A success of topical ruxolitinib (0.6% cream) use in a young patient with AU has been reported to date. Here we report the treatment of a 66-year-old with AA with the same formulation of topical ruxolitinib, where it failed to induce hair growth. Our report demonstrates the importance of examining the factors contributing to variation in treatment response in a clinical trial of topical JAK inhibitors in AA. It is likely that both intrinsic factors specific to individual patients and extrinsic factors relating to treatment regimen are involved. Furthermore, characterisation of the specific JAKs overexpressed in AA may better target medication. Finally, this report highlights the need to compare the outcomes of topical vs oral ruxolitinib administration in patients with severe AA, AT, and AU and may support the possibility that extensive disease is more adequately treated with oral administration of ruxolitinib.

scholarly journals Role of Janus Kinase Inhibitors in Therapy of Psoriasis

2021 ◽  
Vol 10 (19) ◽  
pp. 4307
Author(s):  
Sylwia Słuczanowska-Głąbowska ◽  
Anna Ziegler-Krawczyk ◽  
Kamila Szumilas ◽  
Andrzej Pawlik
Keyword(s):  
Side Effects ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Biologic Drugs ◽  
Janus Kinases ◽  
Janus Kinase Inhibitors ◽  
Long Term Treatment

Janus kinases inhibitors are molecules that target Janus kinases—signal transducers and activators of transcription (JAK/STAT). They inhibit this intracellular signal pathway, blocking the gene transcription of crucial proinflammatory cytokines that play a central role in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. This process reduces psoriatic inflammation. The JAK inhibitors are divided into two generations. The first generation of JAK inhibitors blocks two or more different Janus kinases. The second generation is more specified and blocks only one type of Janus kinase and has less side effects than the first generation. Tofacitinib, ruxolitinib and baricitinib belong to first generation JAK inhibitors and decernotinib and filgotinib belong to second group. This narrative review summarizes the role of Janus kinase inhibitors in the therapy of psoriasis. Oral JAK inhibitors show promise for efficacy and safety in the treatment of psoriasis. Studies to date do not indicate that JAK inhibitors are superior to recent biologic drugs in terms of efficacy. However, JAK inhibitors, due to their lack of increased incidence of side effects compared to other biologic drugs, can be included in the psoriasis treatment algorithm because they are orally taken. Nevertheless, further studies are needed to evaluate long-term treatment effects with these drugs.

scholarly journals Menorrhagia in Women After the Administration of Novel Oral ‎Anticoagulants, Like Rivaroxaban: A Case Report

2020 ◽  
Vol 10 (3) ◽  
pp. 29640
Author(s):  
Jalil ‎ Feizi ◽  
Ali Nazari ◽  
Abbas ‎ Ghaysouri ◽  
Mahtab Bonyadi ◽  
Elham Shafiei
Keyword(s):  
Adverse Effect ◽  
Case Report ◽  
Side Effects ◽  
Vaginal Bleeding ◽  
Oral Anticoagulants ◽  
Ease Of Use ◽  
Novel Oral Anticoagulants ◽  
The Novel ◽  
Case Presentation ◽  
Drug Involvement

Background: The Novel Oral Anticoagulants (NOACs), despite numerous benefits, such as the ease of use and less drug involvement, provide extensive adverse effects. One of the most significant, but rare side effects of them in women is severe and dangerous bleeding. Case presentation: In this study, we reported a case of severe vaginal bleeding (manometric hemorrhage) in a woman receiving rivaroxaban to prevent pulmonary thrombosis. Conclusion: The oral anticoagulant rivaroxaban could present a rare adverse effect on women.  

scholarly journals Spleen and Symptom Responses of JAK Inhibitors in Myelofibrosis; A Systematic Review of Phase 2 and 3 Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Muhammad Ans Sharif ◽  
Muhammad Salman Faisal ◽  
Yazan Samhouri ◽  
Laila Hashim ◽  
Muhammad Yasir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Phase Ii ◽  
Janus Kinase ◽  
Phase Iii ◽  
Symptom Improvement ◽  
Jak Inhibitors ◽  
Phase Ii Trials ◽  
Phase Iii Trials ◽  
Symptom Response

Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth factors. An abnormal upregulation of this pathway is seen in myeloproliferative disorders, especially the classic BCR-ABL negative myelofibrosis (MF). Janus kinase inhibitors (JAKi) have been evaluated in various clinical trials regarding their efficacy in improving the outcomes for MF patients. In this review, we looked at the reduction of splenomegaly and symptom improvement as markers for efficacy of JAKi. Methods: We did a comprehensive literature search, following PRISMA guidelines, on PubMed, Cochrane, clinicaltrials.gov and Embase databases. We used MeSH terms and related keywords for MF and JAKi, including generic and trade names. We screened 3261 articles and selected 23 trials for our study. Case reports, case series, meta-analysis, review articles, observational studies, phase I trials and studies not reporting spleen response were excluded. Spleen and symptom responses were used to determine the efficacy of JAK inhibitors. Spleen volume reduction (SVR) by >35%, spleen length reduction (SLR) by >50% and total symptom score (TSS) improvement by >50% were set as benchmarks for a positive response. Results: We included 23 trials (n= 4739) in our review. There were 15 phase II trials (n=964) and 8 phase III trials (n=3775). Of these 23 trials, 7 trials (n=598) included patients with median age below 65 years, while 16 trials (n=4141) included patients of median age more than 65 years. Of the 9 of trials of ruxolitinib, 4 were phase III trials (n= 2809) and 5 were phase II trials (n= 416). The dose of ruxolitinib used in these trials ranged from 5 mg twice daily to 20 mg twice daily. The percentage of patients who achieved spleen response ranged from 15.6% to 71.7%. There were 5 trials (n= 861) that evaluated efficacy of momelotinib. Three were phase II trials (n= 221), while 2 were phase III trials (n=326). The doses ranged from 150mg to 300mg. The splenic response in patients ranged from 7% to 48%. In one phase 3 randomized control trial, efficacy of momelotinib (N=215)and roxulotinib (N=217) were compared, and were found to be equally efficacious in terms of spleen response (26.5% in the momelotinib group while 29% in the ruxolitinib group) and symptom response (28.4% in the momelotinib group and 42.2% in the ruxolitinib group). In 4 trials (n= 453) of fedratinib, there were 2 phase II trials (n= 127) and 2 phase III trials (n=326). The splenic response ranged from 31% to 73% of the patient population. In phase II JAKARTA2 study, patients who were resistant or intolerant to ruxolitinib showed SVR of 31%. Lestaurtunib, Ilgitanib, pacritinib and itacitinib were studied in 2,1,1, and 1 phase II trials, respectively. The splenic response was 75%, 31%, 31%, and 68.8% respectively. Symptom response was reported in 12 studies (N=1477). The percentage of patients who achieved symptom response receiving roxulotinib were 20.8-49%, momelotinib (28.4-30.7%), ictatinib (51.1-59.4%), practinib (48%), and fedratinib (27-36%). In terms of safety, the most common hematological side effects seen were anemia (15% - 65%), thrombocytopenia (1.3% - 64%) and neutropenia (1% - 28%). These side effects were seen equally with different medications. The most common non hematological adverse effects included diarrhea (4% - 32%), abdominal pain (2.6% - 27.1%) and fatigue (1.3% - 10%). Conclusion Splenomegaly and associated symptoms are major source of morbidity in MF patients. The rapid advancement in novel agents in the last decade changed the treatment paradigm in this disorder. Our systematic review summarizes the effect of JAKi on spleen and symptom responses. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Karyopharm: Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Janssen: Speakers Bureau.

scholarly journals Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors

2020 ◽  
Vol Volume 13 ◽  
pp. 131-139
Author(s):  
Edoardo Troncone ◽  
Irene Marafini ◽  
Giovanna Del Vecchio Blanco ◽  
Antonio Di Grazia ◽  
Giovanni Monteleone
Keyword(s):  
Ulcerative Colitis ◽  
Janus Kinase ◽  
Therapeutic Options ◽  
Jak Inhibitors ◽  
Recent Developments ◽  
Novel Therapeutic

scholarly journals Janus kinases to jakinibs: from basic insights to clinical practice

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_1) ◽  
pp. i4-i16 ◽  
Author(s):  
Massimo Gadina ◽  
Mimi T Le ◽  
Daniella M Schwartz ◽  
Olli Silvennoinen ◽  
Shingo Nakayamada ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Janus Kinase ◽  
Intracellular Signalling ◽  
Cytokine Receptors ◽  
Next Generation ◽  
Jak Inhibitors ◽  
Janus Kinases

AbstractCytokines are critical mediators of diverse immune and inflammatory diseases. Targeting cytokines and cytokine receptors with biologics has revolutionized the treatment of many of these diseases, but targeting intracellular signalling with Janus kinase (JAK) inhibitors (jakinibs) now represents a major new therapeutic advance. We are still in the first decade since these drugs were approved and there is still much to be learned about the mechanisms of action of these drugs and the practical use of these agents. Herein we will review cytokines that do, and just as importantly, do not signal by JAKs, as well as explain how this relates to both efficacy and side effects in various diseases. We will review new, next-generation selective jakinibs, as well as the prospects and challenges ahead in targeting JAKs.

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

2019 ◽  
Vol 23 (3) ◽  
pp. 289-297 ◽  
Author(s):  
Erika L. Crowley ◽  
Shamone C. Fine ◽  
Kathleen Kwan Katipunan ◽  
Melinda J. Gooderham
Keyword(s):  
Case Studies ◽  
Health Care Providers ◽  
Alopecia Areata ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Janus Kinase ◽  
Care Providers ◽  
Jak Inhibitors ◽  
Open Label

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.

scholarly journals Translational Positioning of Janus Kinase (JAK) Inhibitors in Alopecia Areata

EBioMedicine ◽  
2015 ◽  
Vol 2 (4) ◽  
pp. 282-283 ◽  
Author(s):  
Ulrike Blume-Peytavi ◽  
Annika Vogt
Keyword(s):  
Alopecia Areata ◽  
Janus Kinase ◽  
Jak Inhibitors

“What Freedom?”

2019 ◽  
Vol 74 (3) ◽  
pp. 305-331
Author(s):  
John Owen Havard
Keyword(s):  
South America ◽  
French Revolution ◽  
The Political ◽  
The Novel ◽  
Free Condition ◽  
Narrative Design ◽  
Economic Liberalism ◽  
History Of ◽  
Ways Of Thinking ◽  
John Owen

John Owen Havard, “‘What Freedom?’: Frankenstein, Anti-Occidentalism, and English Liberty” (pp. 305–331) “If he were vanquished,” Victor Frankenstein states of his monstrous creation in Mary Shelley’s Frankenstein (1818), “I should be a free man.” But he goes on: “Alas! what freedom? such as the peasant enjoys when his family have been massacred before his eyes, his cottage burnt, his lands laid waste, and he is turned adrift, homeless, pennyless, and alone, but free.” Victor’s circumstances approximate the deracinated subject of an emergent economic liberalism, while looking to other destitute and shipwrecked heroes. Yet the ironic “freedom” described here carries an added charge, which Victor underscores when he concludes this account of his ravaged condition: “Such would be my liberty.” This essay revisits the geographic plotting of Frankenstein: the digression to the East in the nested “harem” episode, the voyage to England, the neglected episode of Victor’s imprisonment in Ireland, and the creature’s desire to live in South America. Locating Victor’s concluding appeal to his “free” condition within the novel’s expansive geography amplifies the political stakes of his downfall, calling attention to not only his own suffering but the wider trail of destruction left in his wake. Where existing critical accounts have emphasized the French Revolution and its violent aftermath, this obscures the novel’s pointed critique of a deep and tangled history of English liberty and its destructive legacies. Reexamining the novel’s geography in tandem with its use of form similarly allows us to rethink the overarching narrative design of Frankenstein, in ways that disrupt, if not more radically dislocate, existing rigid ways of thinking about the novel.

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