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    Palmoplantar Pustulosis-like Eruption Induced by Baricitinib for Treatment of Rheumatoid Arthritis. European journal of case reports in internal medicine OBJECTIVES:Baricitinib is an orally active Janus kinase (JAK) inhibitor used in the treatment of moderate to severe rheumatoid arthritis (RA). MATERIALS AND METHODS:Here, we report the case of a 56-year-old Caucasian male diagnosed with RA who developed palmoplantar pustulosis (PPP) while being treated with baricitinib. RESULTS:The patient's PPP resolved after discontinuation of baricitinib and recurred when this was restarted. Based on causality assessment, it was considered a drug-induced PPP. CONCLUSION:To the authors' knowledge, this is the first case of baricitinib-induced PPP. LEARNING POINTS:Baricitinib is a small, orally active molecule that inhibits JAK-1 and JAK-2, which is used in the treatment of rheumatoid arthritis.Baricitinib has been also used in the treatment of psoriasis, alopecia areata and atopic dermatitis.Palmoplantar pustulosis is a rare cutaneous side effect of baricitinib. 10.12890/2019_001383
    Delgocitinib: First Approval. Dhillon Sohita Drugs Delgocitinib, a janus kinase (JAK) inhibitor, is being developed by Japan Tobacco for the treatment of autoimmune disorders and hypersensitivity, including inflammatory skin conditions. The JAK family of tyrosine kinases plays an important role in mediating the biological effects of several inflammatory cytokines, e.g. IL-4, IL-13 and IL-31, which are elevated in patients with atopic dermatitis. Delgocitinib inhibits all members of the JAK family [JAK1, JAK2, JAK3 and tyrosine kinase 2]. Topical delgocitinib (Corectim) is approved in Japan for the treatment of atopic dermatitis. This article summarizes the milestones in the development of delgocitinib leading to this first approval for the treatment of adults with atopic dermatitis. Clinical development of the topical formulation is also underway for alopecia areata, chronic hand eczema, discoid lupus erythematosus, inverse psoriasis and atopic dermatitis in several countries worldwide. Clinical development of an oral formulation of delgocitinib is also underway in Japan for the treatment of autoimmune disorders and hypersensitivity. 10.1007/s40265-020-01291-2
    Apremilast for extensive and treatment-resistant alopecia areata: a retrospective analysis of five patients. Weber Benedikt,Radakovic Sonja,Tanew Adrian European journal of dermatology : EJD BACKGROUND:Recent experimental data suggest a role for apremilast in the treatment of alopecia areata. Small clinical studies have so far provided contradictory results. OBJECTIVES:We retrospectively evaluated the efficacy and safety of apremilast in five cases of extensive and treatment-resistant alopecia areata. MATERIALS AND METHODS:Apremilast was given at a dose of 30 mg, twice daily, over six months. The efficacy of apremilast treatment was determined by monthly assessment of the affected scalp surface area using SALT scoring. RESULTS:In four out of five patients, no sustained improvement in SALT score was observed within the treatment period. Two of these patients had a slight but only transient improvement after two months of treatment. One patient responded to apremilast treatment with a progressive and marked improvement, as reflected by an 83% reduction in SALT score. CONCLUSION:Our results are in line with the varying treatment responses in previous studies. Future studies on the efficacy of apremilast treatment in confirmed alopecia areata patient groups are warranted. 10.1684/ejd.2020.3749
    Unexpected Hair Regrowth in a Patient with Longstanding Alopecia Universalis During Treatment of Recalcitrant Dermatomyositis with the Janus Kinase Inhibitor Ruxolitinib. Fetter Tanja,Rios German Cuevas,Niebel Dennis,Bieber Thomas,Wenzel Jörg Acta dermato-venereologica is missing (Short communication). 10.2340/00015555-3481
    New and Emerging Therapies for Alopecia Areata. Drugs Alopecia areata (AA) is an autoimmune condition that affects up to 2% of the general population. Currently available treatment options for AA are of limited efficacy and can be associated with adverse effects. The advancement in understanding of the genetic and molecular mechanisms of AA has led to the development of novel treatment options, with the Janus kinase (JAK) inhibitor class of drugs at the forefront of ongoing clinical trials. Platelet-rich plasma, fecal transplants, and cytokine-targeted therapy with ustekinumab and dupilumab have also been shown to regrow hair in patients with AA in individual case reports or small studies. Several other novel therapies have preliminary data or are being tested in clinical trials. 10.1007/s40265-020-01293-0
    Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation. Glickman Jacob W,Dubin Celina,Renert-Yuval Yael,Dahabreh Dante,Kimmel Grace W,Auyeung Kelsey,Estrada Yeriel D,Singer Giselle,Krueger James G,Pavel Ana B,Guttman-Yassky Emma Journal of the American Academy of Dermatology BACKGROUND:Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile. OBJECTIVE:To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity. METHODS:In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49). RESULTS:Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy. LIMITATIONS:Our analysis was limited to 350 proteins. CONCLUSION:This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches. 10.1016/j.jaad.2020.04.138
    The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells. Kim Jung Eun,Lee Yu Jin,Park Hye Ree,Lee Dong Geon,Jeong Kwan Ho,Kang Hoon International journal of molecular sciences Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/β-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/β-catenin signaling pathway, including 1 and , and suppressed the transcription of in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of , , , and , and stimulated several growth factors, such as . Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/β-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege. 10.3390/ijms21145137
    Improvement of Psoriasis, Psoriatic Arthritis, and Alopecia Universalis during Treatment with Tofacitinib: A Case Report. Todberg Tanja,Loft Nikolai Dyrberg,Zachariae Claus Case reports in dermatology Alopecia areata (AA) is the most common immune-mediated hair loss disorder with a life-time prevalence of 2%. The pathogenesis of AA is not completely understood, but interferon gamma (INF-γ) and Janus kinases (JAK) may play a key role. Here, we present a case involving a male patient with psoriasis and psoriatic arthritis, who exhibited a rapid hair loss, diagnosed as AA, during ciclosporin treatment. As ciclosporin was unable to control his psoriasis, the treatment was changed to methotrexate injections, but the hair loss progressed into alopecia universalis. During treatment with the oral JAK inhibitor tofacitinib, the patient presented an almost complete hair remission on the scalp and partly on the eyebrows, eyelashes, beard, and chest. Furthermore, the patient experienced no joint complaints and his psoriasis was improved. Based on these findings, JAK inhibitors may be an optional treatment in complicated cases involving both rheumatological and dermatological diseases. 10.1159/000508782
    Enhancing intradermal delivery of tofacitinib citrate: Comparison between powder-loaded hollow microneedle arrays and dissolving microneedle arrays. Cárcamo-Martínez Álvaro,Mallon Brónach,Anjani Qonita Kurnia,Domínguez-Robles Juan,Utomo Emilia,Vora Lalit K,Tekko Ismael A,Larrañeta Eneko,Donnelly Ryan F International journal of pharmaceutics Autoimmune-mediated inflammatory skin diseases, such as psoriasis, alopecia areata, and vitiligo, have been reported as the 4th leading cause of nonfatal disease burden worldwide. This is mainly related to the poor quality of life experienced by these patients. Although topical and systemic steroids represent the most common treatment, the variability in success rates and side effects often lead to treatment discontinuation. Recent off-label clinical studies using oral Janus Kinase (JAK) inhibitors (e.g., ruxolitinib, tofacitinib, baraticinib) have shown promising results. However, frequent side effects, such as infections and blood clots have been reported. Therefore, the aim of this research was to enhance the intradermal delivery of tofacitinib citrate with MN arrays. Using crosslinked hydrogels containing modifying agents (urea, sorbitol and sodium chloride), hollow MN arrays were fabricated and then loaded with tofacitinib citrate. Their efficiency in intradermal delivery of tofacitinib was compared with dissolving MN arrays and a control (Aqueous cream BP), using neonatal porcine skin. Despite the fact that the hydrogel was only present on the outer surface, hollow MN arrays showed comparable resistance to compression values and insertion capabilities to dissolving MN arrays. Although hollow MN arrays containing NaCl in the formulation led to slightly higher depositions of tofacitinib in epidermis and dermis of neonatal porcine skin when compared to a control cream, dissolving MN arrays showed superiority in terms of tofacitinib deposition in the dermis. Indeed, at 24 h of the study, control cream and dissolving MN arrays delivered 143.98 ug/cm and 835 ug/cm of drug in the dermis, respectively, confirming the enhanced intradermal drug delivery capacity of MN arrays and their potential for treatment of autoimmune skin diseases. 10.1016/j.ijpharm.2020.120152
    Clinical Experience with Oral Tofacitinib in a Patient with Alopecia Areata Universalis and Rheumatoid Arthritis. Abe Daniele Tiemi,Tashima Letícia Mari,Basilio Flavia Machado Alves,Mulinari-Brenner Fabiane International journal of trichology Alopecia areata (AA) is a chronic and autoimmune disease frequently characterized by a challenge management between dermatologists. At present, JAK-inhibitors have demonstrated encouraging results in AA treatment. Therefore, this study reports a case of alopecia universalis in a patient with rheumatoid arthritis (RA), whose methotrexate therapy shown unsatisfactory response in RA control. After the introduction of 10 mg (oral route) per day of tofacitinib, a JAK-inhibitor, an improvement of almost 50% in severity alopecia tool score occurred with maintained response even after 3 months of medication suspension. From this time, we corroborate the effectiveness of JAK-inhibitors presented in the scientific literature. In addition, we inquiry the real impact of methotrexate on JAK-start signaling inhibition in AA pathophysiology. 10.4103/ijt.ijt_107_20
    Therapeutic management in paediatric alopecia areata: A systematic review. Waśkiel-Burnat A,Kołodziejak M,Sikora M,Stochmal A,Rakowska A,Olszewska M,Rudnicka L Journal of the European Academy of Dermatology and Venereology : JEADV Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic review of the literature about the treatment of alopecia areata in children (≤18 years old) was performed on 11 May 2020 by searching the PubMed, Scopus and EBSCO databases. The terms used for the search were: 'alopecia areata', 'alopecia totalis' or 'alopecia universalis' combined with 'paediatric', 'children' or 'childhood'. A total of 89 articles were included in final evaluation. The most commonly assessed treatment options in paediatric alopecia areata were topical immunotherapy (response rate in monotherapy: 54%; 187/345) intralesional glucocorticosteroids (75%; 211/280), systemic glucocorticosteroids (73%; 102/140), and anthralin (42%; 31/74). Topical glucocorticosteroids (81%; 35/43), systemic Janus kinase (JAK) inhibitors (90%; 27/30), topical calcineurin inhibitors (42%; 8/19), topical JAK inhibitors (65%; 11/17), PUVA therapy (56%; 9/16) and 308-nm excimer laser (77%; 10/13) were also evaluated. Additionally, evaluation in smaller numbers of paediatric patients included methotrexate (100%; 10/10), topical minoxidil (44%; 4/9) and cyclosporine (83%; 5/6). There were limited data considering children with alopecia areata treated with azathioprine, hydroxychloroquine, topical sildenafil, topical prostaglandin analogues, fractional carbon dioxide laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab, botulinum toxin, and compound glycyrrhizin. On the basis of the limited data available glucocorticosteroids (systemic, intralesional or topical) and JAK inhibitors (systemic or topical) may be considered the best documented and most effective treatment options in alopecia areata in children. There are no sufficient paediatric data to compare treatment safety and relapse rates in these therapeutic modalities. 10.1111/jdv.17187
    Pediatric Game Changers∗: Oral tofacitinib for the treatment of alopecia areata in children. Kamath Sonia Journal of the American Academy of Dermatology 10.1016/j.jaad.2021.02.014
    A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. King Brett,Guttman-Yassky Emma,Peeva Elena,Banerjee Anindita,Sinclair Rodney,Pavel Ana B,Zhu Linda,Cox Lori Ann,Craiglow Brittany,Chen Linda,Banfield Christopher,Page Karen,Zhang Weidong,Vincent Michael S Journal of the American Academy of Dermatology BACKGROUND:Alopecia areata (AA) is an autoimmune form of hair loss with limited treatments. OBJECTIVE:To evaluate the efficacy and safety of the Janus kinase inhibitors ritlecitinib and brepocitinib in patients who have AA with ≥ 50% scalp hair loss. METHODS:Patients were randomized to once-daily ritlecitinib, brepocitinib, or placebo. The primary efficacy endpoint was a 24-week change from baseline in the Severity of Alopecia Tool (SALT) score. The key secondary efficacy endpoint was the proportion of patients achieving 30% improvement in SALT score (SALT). RESULTS:The ritlecitinib, brepocitinib, and placebo groups included 48, 47, and 47 patients, respectively. At week 24, least-squares mean difference from placebo in SALT score change from baseline was 31.1 (95% confidence interval [CI], 18.8-43.5) for ritlecitinib and 49.2 (95% CI, 36.6-61.7) for brepocitinib (P < .0001 for both comparisons with placebo). SALT was achieved by 50% (90% CI, 38%-62%) of patients receiving ritlecitinib, 64% (90% CI, 51%-75%) receiving brepocitinib, and 2% (90% CI, 0%-9%) receiving placebo. Two patients experienced a serious adverse event (rhabdomyolysis) in the brepocitinib group only. LIMITATIONS:Only a single-dosage regimen of each study drug was included. CONCLUSION:Treatment with ritlecitinib or brepocitinib for 24 weeks was efficacious and generally well tolerated. 10.1016/j.jaad.2021.03.050
    Topical tofacitinib for the treatment of alopecia areata affecting facial hair. Kerkemeyer K L S,Sinclair R D,Bhoyrul B The British journal of dermatology 10.1111/bjd.20419
    Sublingual tofacitinib for alopecia areata: a roll-over pilot clinical trial and analysis of pharmacokinetics. International journal of dermatology Tofacitinib is a JAK1/3 inhibitor used off-label to treat alopecia areata (AA). Oral tofacitinib undergoes extensive hepatic metabolism and has numerous drug interactions and a half-life of 3 hours necessitating twice daily dosing. Sublingual delivery bypasses hepatic first-pass metabolism, which may provide pharmacokinetic benefits and reduce gastrointestinal side effects. We investigate sublingual tofacitinib as a novel form of administration in a cohort of treatment-resistant patients. The objective of this work is to assess the efficacy and pharmacokinetics of sublingual tofacitinib in moderate-to-severe AA patients. An open-label, roll-over pilot clinical trial was conducted. Participants were recruited from a preceding trial. All responders (≥50% reduction in Severity of Alopecia Tool [SALT] score, SALT50) in the preceding trial continued on the same treatment (cyclosporine/placebo), whereas nonresponders rolled over to receive open-label sublingual tofacitinib 5 mg twice daily for 12 weeks. Treatment response as reduction in SALT score after 12 weeks (low: 15-29%, medium: 30-49%, good: 50-75%, and high grade: 75-100%) was measured. Pharmacokinetics was analyzed using liquid chromatography tandem mass spectrometry. Eighteen participants completed the trial. Total treatment response to tofacitinib was 37.5%. SALT50 was achieved in 12.5%. The mean improvement in SALT score was 15.57%. Mean maximum plasma concentration was 43.18 ng/ml occurring after 1 hour. Elimination half-life is estimated to be up to 11 hours. An estimated half-life of up to 11 hours may be achieved with sublingual tofacitinib, which is significantly longer than the oral form and may facilitate daily dosing. Larger clinical trials are required to further characterize its pharmacokinetics and efficacy. 10.1111/ijd.15657
    Alopecia Areata: New Treatment Options Including Janus Kinase Inhibitors. Zheng Caiwei,Tosti Antonella Dermatologic clinics Alopecia areata (AA) is a chronic, relapsing, autoimmune disorder characterized by patchy nonscaring hair loss. Although the pathogenesis of alopecia areata is not yet completely elucidated, loss of immune privilege in anagen stage hair follicles is widely accepted to play a key role. Several cytokines that depend on Janus kinase signaling have been identified to be involved in AA, including interleukin (IL)-2, IL-7, IL-15, IL-21, and interferon-γ, making Janus kinase inhibitors an attractive therapeutic target. Available information indicates that about 70% of patients with AA experience significant regrowth, but interruption of treatment is associated with disease recurrence. 10.1016/j.det.2021.03.005
    Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: Phase 2 results from a randomized controlled study. King Brett,Ko Justin,Forman Seth,Ohyama Manabu,Mesinkovska Natasha,Yu Guanglei,McCollam Jill,Gamalo Margaret,Janes Jonathan,Edson-Heredia Emily,Holzwarth Katrin,Dutronc Yves Journal of the American Academy of Dermatology BACKGROUND:There are no treatments approved by the Food and Drug Administration for alopecia areata. OBJECTIVE:To evaluate the efficacy and safety of baricitinib in patients with ≥50% scalp hair loss in a phase 2 study of adults with alopecia areata (BRAVE-AA1). METHODS:Patients were randomized 1:1:1:1 to receive placebo or baricitinib 1 mg, 2 mg, or 4 mg once daily. Two consecutive interim analyses were performed after all patients completed weeks 12 and 36 or had discontinued treatment prior to these time points. The primary endpoint was the proportion of patients achieving a Severity of Alopecia Tool (SALT) score ≤20 at week 36. Logistic regression was used with nonresponder imputation for missing data. RESULTS:A total of 110 patients were randomized (placebo, 28; baricitinib 1-mg, 28; 2-mg, 27; 4-mg, 27). The baricitinib 1-mg dose was dropped after the first interim analysis based on lower SALT response rate. At week 36, the proportion of patients achieving a SALT score of ≤20 was significantly greater in baricitinib 2-mg (33.3%, P = .016) and 4-mg (51.9%, P = .001) groups versus placebo (3.6%). Baricitinib was well tolerated with no new safety findings. LIMITATIONS:Small sample size limits generalizability of results. CONCLUSION:These results support the efficacy and safety of baricitinib in patients with ≥50% scalp hair loss. 10.1016/j.jaad.2021.05.050
    A Comprehensive Literature Review of JAK Inhibitors in Treatment of Alopecia Areata. Dillon Kerry-Ann L Clinical, cosmetic and investigational dermatology Alopecia areata (AA) is a chronic, immune-mediated form of nonscarring alopecia that is multifactorial and results in localized patches. It is often described as a self-limiting condition that results in the spontaneous regrowth of hair in most cases. However, this regrowth may take several months or years to occur in some patients, leading to the development of psychoemotional trauma in those that are affected. Although several therapies for AA have been developed and tested, there is no specific treatment that has been approved, leading to the availability of many off-label conventional treatment options, with very limited responses. More recently, with the advancement of pre-clinical and genetic studies, a greater understanding of the pathomechanisms involved in the development of AA has been uncovered. This has resulted in the introduction of targeted therapies that use small molecules to block specific pathways involved in AA pathophysiology. As such, the use of janus kinase (JAK) inhibitors for treatment of AA has emerged. JAK inhibitors block the T-cell mediated inflammatory response thought to be the driving factor behind AA pathogenesis, by inhibiting the janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway, leading to a reversal of hair loss in AA patients. Thus, in an effort to demonstrate the efficacy of JAK inhibitors in the treatment of AA, several studies have been published within recent years. However, the question remains, "Are JAK inhibitors effective and safe in the management of Alopecia Areata?". This review aims to provide a comprehensive report on the role, efficacy, and outcomes of using JAK inhibitors in the treatment of AA. To competently answer the research question highlighted, the most recent, quality articles published over a 10-15-year period were sourced using PubMed, NCBI, Research gate, Medline, Cochrane Central Register of Controlled Trials, EMBASE and Google scholar. The literature search was primarily focused on randomized controlled trials (RCTs); however, in the absence of such, only the most recently published case reports, case series, clinical trials and open-label studies published to date were included. 10.2147/CCID.S309215
    Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis. Yu Da-Ae,Kim Ye Eun,Kwon Ohsang,Park Hyunsun Indian journal of dermatology, venereology and leprology BACKGROUND:Tofacitinib and ruxolitinib have been used off-label to treat alopecia areata. Although a number of case reports and small studies have been published, there are no comprehensive reviews examining the outcomes of using tofacitinib and ruxolitinib for the treatment of alopecia areata. AIMS:The aim of the study was to examine the outcome of patients with alopecia areata treated with oral tofacitinib or ruxolitinib in previously published studies. METHODS:A search of MEDLINE, Embase and Cochrane library was conducted. A systematic review and meta-analysis were performed focusing on the Severity of Alopecia Tool 50 achievement rate, the frequency of adverse events and recurrence after discontinuation of treatment. RESULTS:A total of 1244 studies were identified of which only 12 studies met the inclusion criteria. Of the 346 patients in these 12 studies, 288 had received oral tofacitinib and 58 had received oral ruxolitinib. The overall Severity of Alopecia Tool50 achievement rate was 66% (95% confidence interval, 54%-76%). Subgroup analysis revealed that drug choice, mean age, sex ratio and alopecia areata subtype ratio did not significantly affect the treatment response. Infections and laboratory abnormalities were the most common adverse events (98 and 65 cases of 319 patients, respectively). Patients treated for more than six months had a greater frequency of laboratory abnormalities as compared to those treated for shorter durations (24% vs. 7%; P = 0.04). Recurrence of alopecia areata was observed within three months after discontinuation of treatment in the majority (74%) of patients. LIMITATIONS:This analysis was limited by the small number of observational studies available for review, the heterogeneity of patient characteristics and the lack of long-term data. CONCLUSION:Both oral tofacitinib and ruxolitinib are effective and well tolerated in the treatment of alopecia areata. Clinicians should be aware of the expected efficacy, adverse events and high recurrence rate of oral JAK inhibitors for alopecia areata to effectively counsel these patients before starting therapy. 10.25259/IJDVL_975_19
    Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management. Zhou Cheng,Li Xiangqian,Wang Chen,Zhang Jianzhong Clinical reviews in allergy & immunology Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease, resulting in hair loss, that affects up to 2% of the general population. The exact pathobiology of AA has still remained elusive, while the common theory is the collapse of the immune privilege of the hair follicle caused by immunological mechanism. Multiple genetic and environment factors contribute to the pathogenesis of AA. There are several clinical treatments for AA, varying from one or multiple well-defined patches to more diffuse or total hair loss of the scalp (alopecia totalis) or hair loss of the entire body (alopecia universalis). The available treatments for AA, such as corticosteroids and other immunomodulators, minoxidil, and contact immunotherapy, are of limited efficacy with a high risk of adverse effects and high recurrence rates, especially for patients with severe AA. Recent insights into the pathogenesis of AA have led to the development of new treatment strategies, such as Janus kinase (JAK) inhibitors, biologics, and several small molecular agents. In addition, modern therapies for AA, including antihistamines, platelet-rich plasma (PRP) injection, and other novel therapies have been well explored. In this review, we discussed the recent advances in the pathogenesis, diagnosis, and treatment of AA. 10.1007/s12016-021-08883-0
    Regulatory network analysis defines unique drug mechanisms of action and facilitates patient-drug matching in alopecia areata clinical trials. Chen James C,Dai Zhenpeng,Christiano Angela M Computational and structural biotechnology journal Not all therapeutics are created equal in regards to individual patients. The problem of identifying which compound will work best with which patient is a significant burden across all disease contexts. In the context of autoimmune diseases such as alopecia areata, several formulations of JAK/STAT inhibitors have demonstrated efficacy in clinical trials. All of these compounds demonstrate different rates of response, and here we observed that this coincided with different molecular effects on patients undergoing treatment. Using these data, we have developed a computational model that is capable of predicting which patient-drug pairs have the highest likelihood of response. We achieved this by integrating inferred mechanism of action data and gene regulatory networks derived from an independent patient cohort with baseline patient data prior to beginning treatment. 10.1016/j.csbj.2021.08.026
    Alopecia areata and tofacitinib: a prospective multicenter study from a Saudi population. International journal of dermatology BACKGROUND:Alopecia areata (AA) is an autoimmune disorder characterized by nonscarring hair loss that can involve the scalp, face, and body. Severe AA subtypes have a poorer prognosis and can be challenging to treat. Tofacitinib, a recently introduced Janus kinase inhibitor, has shown positive results in treating AA. This multicenter study demonstrates the efficacy of tofacitinib and the patient response rate in a Saudi population. It also highlights patient characteristics that may serve as predictors of the therapeutic response to tofacitinib. METHODS:A prospective cohort study design was utilized. Study participants were included from three medical centers in Riyadh, Saudi Arabia. The Severity of Alopecia Tool (SALT) score was used to assess the percentage of hair loss at baseline and the percentage of hair regrowth at 3 and 6 months. RESULTS:The sample size was 68 with an average baseline SALT score of 76.8 ± 27.6%. Data at 6 months were available for 45 patients. Of these, 62.2% achieved a SALT score of >50%. Patients with a score of <50% had a significantly higher baseline SALT score compared to patients with >50% score. The past use of systemic steroids was associated with a diminished response to therapy (P = 0.015). The response to therapy was significantly higher in patients with AA compared to alopecia totalis and alopecia universalis. CONCLUSIONS:Tofacitinib is an effective and well-tolerated treatment for severe AA and exhibits a good safety profile. 10.1111/ijd.15917
    Oral tofacitinib for the treatment of alopecia areata in pediatric patients. Kibbie Jon,Kines Kelsey,Norris David,Dunnick Cory A Pediatric dermatology BACKGROUND:Alopecia areata (AA) is characterized by the loss of hair, often in well-demarcated areas. While the pathogenesis of AA is not entirely understood, it is known that CD8 T cell-mediated destruction of the hair follicle occurs. There are no curative therapies for AA, although several therapies have been utilized with variable results. Oral tofacitinib, a JAK inhibitor, has been demonstrated to be efficacious and well tolerated in the treatment of adult AA. However, few studies have examined the clinical efficacy and tolerability of oral tofacitinib in the treatment of pediatric AA. OBJECTIVE:To summarize the clinical outcomes of pediatric patients with AA treated with oral tofacitinib at the University of Colorado Hospital Dermatology Clinic. METHODS:This is a retrospective case series conducted at the University of Colorado Hospital Dermatology Clinic. We included patients with a diagnosis of AA who were 18 years old or younger at the initiation of tofacitinib therapy. Demographics, treatment response, and adverse events were collected from electronic medical records. RESULTS:Eleven patients (seven females, four males) with AA presented to the University of Colorado Hospital Dermatology Clinic who were between the ages of 8 and 18 years. Eight patients (72.7%) experienced hair regrowth with oral tofacitinib, while three patients (27.3%) experienced minimal to no hair regrowth. There were no serious adverse events recorded in the study population during the observed treatment period. CONCLUSIONS:Oral tofacitinib was clinically effective in the majority our of patients and well tolerated. 10.1111/pde.14855
    Ritlecitinib: an investigational drug for the treatment of moderate to severe alopecia areata. Expert opinion on investigational drugs INTRODUCTION:Alopecia areata (AA) is an inflammatory and autoimmune form of hair loss, which can present with one patch of hair loss, but in more extreme cases can lead to total body hair loss. There are limited therapeutic options and no cure, but medication can sometimes induce sustained remission. Disease control cannot be guaranteed; even those who regrow all hair on treatment can experience relapse. There are no FDA approved systemic treatments; therefore, an unmet need for safe, and effective treatments exists. Few treatments have been evaluated by randomized controlled trials. Case reports and series indicate oral Janus Kinase (JAK) inhibitors as a potential therapy. Ritlecitinib is a novel oral JAK3-selective inhibitor being investigated as an AA treatment. AREAS COVERED:This article introduces ritlecitinib as treatment for AA and considers the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety [reporting data from a 24-week, phase 2a double-blinded placebo-controlled trial of ritlecitinib in patients with AA who have more than 50% scalp hair loss]. EXPERT OPINION:Ritlecitinib offers a novel mode of action, rapid onset, and the capacity for a superior safety profile over other JAK inhibitors. If approved, ritlecitinib will be widely prescribed by physicians overseeing the more severe AA patients for the foreseeable future. As JAK inhibitors regulate the hair growth cycle and have anti-inflammatory effects, the implementation of ritlecitinib in hair loss disorders other than AA, may prove beneficial. 10.1080/13543784.2021.2012149
    Treatment of Crohn's Disease and Concomitant Alopecia Areata With Tofacitinib. Akiyama Shintaro,Lin Austin,Traboulsi Cindy,Rubin David T ACG case reports journal Alopecia areata (AA) is a type of immune-mediated hair loss and is reported in patients with inflammatory bowel disease. This suggests that there might be a shared molecular pathway in the pathogenesis of AA and inflammatory bowel disease. In addition, tumor necrosis factor-alpha antagonists are also rarely associated with new-onset AA. We present a patient with Crohn's disease treated with adalimumab who developed AA that rapidly progressed to alopecia totalis and universalis. We describe the use of tofacitinib, a Janus kinase 1/3 inhibitor, to not only successfully treat the AA but also maintain her Crohn's disease. 10.14309/crj.0000000000000690
    Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers. The Journal of allergy and clinical immunology BACKGROUND:Janus kinase (JAK) inhibitors have shown encouraging results in the treatment of alopecia areata (AA), an autoimmune form of hair loss, in small, uncontrolled studies and case reports. OBJECTIVE:We conducted a biopsy substudy during the randomized, double-blind, placebo-controlled first 24 weeks of a phase 2a clinical trial that evaluated the efficacy and safety of ritlecitinib, an inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and brepocitinib, an inhibitor of tyrosine kinase 2 (TYK2)/JAK1 in the treatment of AA. METHODS:Change in biomarkers in lesional scalp biopsy samples between baseline and weeks 12 and 24 was an exploratory end point, and 46 patients participated from the ritlecitinib (n = 18), brepocitinib (n = 16), and placebo (n = 12) groups. Correlations of biomarkers with hair regrowth, measured using the Severity of Alopecia Tool (SALT) score, were also evaluated. CLINICAL TRIAL REGISTRATION:NCT02974868. RESULTS:At week 24, both ritlecitinib and brepocitinib demonstrated improvement exceeding 100% in the lesional scalp transcriptome toward a nonlesional profile. At week 12, the improvements in scalp tissue were greater with brepocitinib than ritlecitinib; however, at week 24, the improvements were greater with ritlecitinib. CONCLUSIONS:For both ritlecitinib and brepocitinib, improvement in the SALT scores was positively associated with expression of T1 markers and negatively associated with expression of hair keratins. Larger, long-term clinical trials are warranted. 10.1016/j.jaci.2021.10.036
    Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial. Peeva Elena,Guttman-Yassky Emma,Banerjee Anindita,Sinclair Rodney,Cox Lori Ann,Zhu Linda,Zhu Hua,Vincent Michael,King Brett Journal of the American Academy of Dermatology 10.1016/j.jaad.2021.12.008
    Recovery of Alopecia Universalis with Associated Nail Dystrophy Treated with Tofacitinib: A 6-year-old Child's Case Report. Dube Vineet International journal of trichology An emerging treatment modality whose established efficacy in systemic inflammatory diseases is now being actively explored for cutaneous disorders: tofacitinib, an oral Janus kinase inhibitor, is one such treatment. Alopecia universalis has been reported to improve with the use of tofacitinib in various case reports and case series. Nail dystrophy is a diverse skin disorder that has been linked to autoimmune illnesses such as psoriasis and psoriatic arthritis in certain subtypes. Alopecia areata and alopecia universalis are also commonly associated with nail dystrophy. In the present case report, we see that there are also improvements in nail dystrophy in the patient with alopecia universalis who is using tofacitinib. 10.4103/ijt.ijt_91_21
    The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications. Waśkiel-Burnat Anna,Osińska Marta,Salińska Anna,Blicharz Leszek,Goldust Mohamad,Olszewska Małgorzata,Rudnicka Lidia Cells Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy. 10.3390/cells10123397
    Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nature reviews. Rheumatology The four Janus kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) transcription factors mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic and inflammatory diseases. Development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders. JAK inhibitors suppress intracellular signalling mediated by multiple cytokines involved in the pathological processes of rheumatoid arthritis and many other immune and inflammatory diseases, and therefore have the capacity to target multiple aspects of those diseases. In addition to rheumatoid arthritis, JAK inhibition has potential for treatment of autoimmune diseases including systemic lupus erythematosus, spondyloarthritis, inflammatory bowel disease and alopecia areata, in which stimulation of innate immunity activates adaptive immunity, leading to generation of autoreactive T cells and activation and differentiation of B cells. JAK inhibitors are also effective in the treatment of allergic disorders, such as atopic dermatitis, and can even be used for the COVID-19-related cytokine storm. Mechanism-based treatments targeting JAK-STAT pathways have the potential to provide positive outcomes by minimizing the use of glucocorticoids and/or non-specific immunosuppressants in the treatment of systemic immune-mediated inflammatory diseases. 10.1038/s41584-021-00726-8
    Tofacitinib as a pragmatic treatment choice for alopecia areata: A retrospective review. Dermatologic therapy Alopecia areata (AA) is an immune-mediated hair loss disease for which targeted immune treatments including Janus kinase (JAK) inhibitors, for example, tofacitinib, are emerging. More literature is needed on the safety and efficacy of JAK inhibitors, and treatment has the potential to be cost prohibitive. This study was conducted to measure safety and efficacy outcomes of off-label use of tofacitinib in AA. A secondary outcome was analysis of payment methods. We reviewed 35 AA patients treated with tofacitinib in a specialty hair disease clinic between January 2013 and July 2019 for outcomes, adverse events, and feasibility of treatment. No serious adverse events were experienced. 83.9% of patients experienced clinically significant scalp regrowth, and 32.3% experienced near total/total regrowth. Though this study was confined to retrospective analysis, the results showed that tofacitinib was safe, effective, and practical for this cohort of 35 AA patients. 10.1111/dth.15310
    Characterizing the relationships between patient-reported outcomes and clinician assessments of alopecia areata in a phase 2a randomized trial of ritlecitinib and brepocitinib. Winnette R,Banerjee A,Sikirica V,Peeva E,Wyrwich K Journal of the European Academy of Dermatology and Venereology : JEADV BACKGROUND:The phase 2a ALLEGRO trial (NCT02974868) investigated the safety and efficacy of ritlecitinib (PF-06651600) and brepocitinib (PF-06700841) in adults with alopecia areata. No randomized controlled trial for alopecia areata has evaluated correlations between clinician-assessed hair loss and patient-reported outcomes. OBJECTIVES:Report scores from the Alopecia Areata Symptom Impact Scale (AASIS; a patient-reported outcome tool) and explore the relationships of those scores with clinician-assessed Severity of Alopecia Tool (SALT) scores at baseline and week 24 of the ALLEGRO trial. METHODS:Adults with alopecia areata were randomized to ritlecitinib (n = 48), brepocitinib (n = 47) or placebo (n = 47). After 24 weeks, the mixed-effects model with repeated measures was used to calculate the active treatment groups' AASIS score least-squares mean differences. Relationships between AASIS and SALT scores at baseline and week 24 were evaluated by Pearson's correlation coefficients using pooled data. RESULTS:Baseline AASIS and SALT scores were similar among treatment groups. Both active treatment groups reported significant improvements in AASIS scores at week 24 (least-squares mean differences vs. placebo for ritlecitinib, -0.8 to -2.3; brepocitinib, -0.9 to -3.7; P < 0.05 for all). At week 24, the mean SALT scores (standard deviation) improved compared with baseline [ritlecitinib, 54.4 (40.3) vs. 89.4 (15.8); brepocitinib, 31.9 (35.7) vs. 86.4 (18.1)]. The correlation coefficients between AASIS global and subscale scores and SALT scores at week 24 ranged from 0.34 to 0.58; P < 0.05 for all. CONCLUSIONS:Patients randomized to ritlecitinib or brepocitinib reported significantly improved AASIS and SALT scores at week 24 of the ALLEGRO trial compared to placebo. At week 24, medium-to-large correlations can be seen between AASIS global and subscale scores and SALT scores. Our experience with AASIS instrument highlighted several aspects that suggest new patient-reported outcome tools are needed to accurately assess patients' relevant alopecia areata related signs, symptoms and daily functioning. 10.1111/jdv.17909
    [Dermatology - Latest developments in targeted therapies for atopic dermatitis, alopecia areata and chronic spontaneous urticaria]. Piletta-Zanin Aurélie,Hsieh Aurélie,Mühlstädt Michael,Andenmatten-Trigona Béatrice Revue medicale suisse In recent years, a lot of targeted therapies have appeared on the market. The huge choice and rapid development make it sometimes difficult to stay up to date. This article reviews the latest therapies in the field of atopic dermatitis, alopecia areata and chronic spontaneous urticaria. Anti-IL-4 and anti-IL-13 antibodies and, more recently, JAK inhibitors have been proven to be effective for moderate to severe atopic dermatitis. JAK inhibitors seem promising for the treatment of severe alopecia areata. Ligelizumab and nemoli zumab will provide therapeutical options for chronic spontaneous urticaria and prurigo respectively. These breakthroughs will improve the quality of life of people suffering from invalidating dermatitis, at a certain price. 10.53738/REVMED.2022.18.767.156
    Good Efficacy Achieved by Baricitinib in the Treatment of Anti-MDA5 Antibody-positive Dermatomyositis with Alopecia Areata. Chen Dandan,Huang Wenhan,Wang Zhongjie,Ren Feifeng,Luo Lei,Zhou Jun,Huang Dongmei,Tian Mengxue,Tang Lin Rheumatology (Oxford, England) 10.1093/rheumatology/keac084
    Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata. Ramírez-Marín Hassiel Aurelio,Tosti Antonella Drug design, development and therapy Alopecia areata (AA) is an autoimmune condition that causes patchy hair loss, affecting up to 147 million people globally. Currently, there are no treatments approved by US Food and Drug Administration (FDA) specific for AA, and there are few effective therapeutic options for widespread and persistent illness. There is an ongoing need for a treatment that demonstrates a good clinical response with a benefit-risk ratio that is suitable for long-term use, especially for patients with chronic, extensive disease. Several clinical trials and case studies that have assessed Janus kinase inhibitors have had encouraging results. Ritlecitinib, a selective JAK3/TEC kinase inhibitor has been demonstrated to inhibit the action of signaling molecules and immune cells that are responsible for hair loss in people with alopecia areata. Furthermore, several clinical trials are investigating the utility of ritlecitinib in patients with vitiligo, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Advantages of using ritlecitinib when compared with other non-selective JAK inhibitors include avoiding JAK1/JAK2 inhibition's clinical repercussions, which include pharmacodynamic effects such as increased cholesterol and liver enzymes, and those related to JAK2 inhibition (thrombocytopenia, anemia). Treatment with Ritlecitinib 50 mg and 30 mg daily for 24 weeks has been shown to induce hair regrowth with a significant proportion of patients reaching SALT 20 (≤20% scalp hair loss) after six months of therapy compared to placebo. Additional research is needed for long-term effects. 10.2147/DDDT.S334727
    A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata. Mikhaylov Daniela,Glickman Jacob W,Del Duca Ester,Nia John,Hashim Peter,Singer Giselle K,Posligua Alba L,Florek Aleksandra G,Ibler Erin,Hagstrom Erika L,Estrada Yeriel,Rangel Stephanie M,Colavincenzo Maria,Paller Amy S,Guttman-Yassky Emma Archives of dermatological research Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA. 10.1007/s00403-022-02336-0
    [Janus kinase inhibitors for the treatment of alopecia areata]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete Alopecia areata is a common condition that leads to nonscarring hair loss. It can be severe and lead to complete hair loss of the scalp or the whole body. In more severe cases, the disease can be very recalcitrant to treatment and result in a significant impairment of the quality of life of the patients. In recent years, there is increasing evidence on the potential of janus kinase (JAK) inhibitors to treat alopecia areata. In the beginning, this was based on case reports, but later, this potential was further established by large case series and in vitro and in vivo data. It is on this basis that JAK inhibitors are being tested specifically for the treatment of alopecia areata in phase 3, randomized, placebo-controlled trials, raising hopes that there will soon be a JAK inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of alopecia areata. Here we provide a review of the information available on the use of JAK inhibitors to treat alopecia areata, and the potential benefits and risks of this class of medications. 10.1007/s00105-022-04982-x
    Application of Baricitinib in Dermatology. Zhang Jingya,Qi Fei,Dong Jie,Tan Yaqi,Gao Ling,Liu Fang Journal of inflammation research There are four JAK subtypes: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Small molecule Janus tyrosine kinase (JAK) inhibitors can inhibit a variety of pro-inflammatory cytokines. Baricitinib is the first generation of JAK1/2 inhibitor targeting the ATPase of JAK, which blocks the intracellular transmission of cytokines through JAK-STATs. Thus far, it has been approved for the treatment of rheumatoid arthritis (RA); however, an increasing number of studies have suggested that baricitinib can be used to treat dermatological diseases, such as atopic dermatitis (AD), psoriasis, vitiligo, and alopecia areata. Baricitinib can be a new choice for the treatment of dermatological diseases, which cannot be treated with conventional drugs. We reviewed the application, efficacy, side effects, precautions, limitations and prospect of baricitinib in atopic dermatitis, psoriasis, vitiligo and alopecia areata (AA) in recent 5 years including clinical trials and case reports. Among them, the application in the field of alopecia areata is the most encouraging, and we reviewed the mechanism in detail. 10.2147/JIR.S356316
    Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata. Journal of the American Academy of Dermatology BACKGROUND:Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE:To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS:In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS:A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS:These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS:Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA. 10.1016/j.jaad.2022.03.045
    Successful treatment of chronic severe alopecia areata with abrocitinib. The Australasian journal of dermatology 10.1111/ajd.13836
    Treatment of Resistant Alopecia areata with Tofacitinib. International journal of trichology The activity of tofacitinib for Alopecia areata (AA) has been reported but mainly from the western countries. We report the case of a young female Indian patient with AA unresponsive to therapy. Improvements in terms of hair regrowth were observed within 2 months of treatment with oral tofacitinib 5 mg BID tablets. The effectiveness of tofacitinib in hair regrowth was maintained till 5-month follow-up period. There were no side effects reported and the treatment with tofacitinib was well-tolerated. 10.4103/ijt.ijt_128_21
    Tofacitinib for Treatment of Alopecia Areata: Real-world Evidence and Factors Associated with Therapeutic Response. Acta dermato-venereologica 10.2340/actadv.v102.2036
    Systematic review - alopecia areata and tofacitinib in paediatric patients. Cutaneous and ocular toxicology INTRODUCTION:Alopecia Areata is a nonscarring hair loss disorder and is the most common hair loss cause in children. It is a chronic autoimmune disorder with a severe psychological impact in patients' lives. JAK inhibitors, in particular Tofacitinib, have been having promising results on Alopecia Areata Treatment. In this study we aimed to do a Systematic Review on the role of Tofacitinib (either orally or topically), considering efficacy and safety, in treating children with Alopecia Areata. MATERIALS AND METHODS:PubMed, Cochrane and Web of Science databases were searched (up to 1st of September of 2021) looking for Tofacitinib (all text/all fields) and MeSH/Keyword term Alopecia Areata. RESULTS AND CONCLUSIONS:We included 14 studies and 64 cases in the Systematic Review. From these, 12 were considering systemic administration (47 patients) and two were considering topical administration (17 patients). Responsiveness was as high as 81.3%. The responsiveness was similar among different genders (78.6% in males and 80.0% in females) and either whether administration was topic (70.6% responsiveness) or systemic (85.1% responsiveness). Adverse effects were rare and, when present, were mild. Studies shows promising results in what considers the efficacy and safety of Tofacitinib in the treatment of Alopecia Areata. As the available evidence to date is of low quality, further randomised studies are required to confirm these findings. 10.1080/15569527.2022.2084622