piperidines and Alopecia-Areata

Topics: Alopecia; Alopecia Areata; Humans; Piperidines

Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and safe. Recent studies have demonstrated the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in adult patients with AA, whereas data on paediatric patients with AA in real-world practice are limited. This was a single-centre, retrospective study that included 11 pre-adolescent patients with AA treated with tofacitinib between December 2021 and September 2022. Clinical characteristics of patients, clinical response and adverse events were evaluated. Overall, 82% (9/11) of patients experienced hair regrowth and 64% (7/11) of patients experienced over 50% improvement in their Severity of Alopecia Tool (SALT) scores. Adverse events were mild. In the literature, tofacitinib has been used to treat AA in 31 children ≤12 years of age who failed to respond to prior treatments. Eighty-seven percent (27/31) of these patients showed significant responses based on changes in their SALT scores. This case series demonstrates that oral tofacitinib is an effective and safe treatment option for paediatric AA, particularly for children who have failed to respond to traditional treatments or are not suitable for such treatments.

Topics: Adolescent; Adult; Alopecia Areata; Child; Humans; Janus Kinase Inhibitors; Piperidines; Retrospective Studies

Tofacitinib has revolutionized the treatment of numerous dermatological conditions in different age groups. However, evidence for its effectiveness, safety and tolerability in the paediatric population is limited. We performed a literature search, which showed that oral tofacitinib is a reliable option in refractory juvenile dermatomyositis, severe alopecia areata, atopic dermatitis and psoriasis. Topical tofacitinib is an effective option in vitiligo and halo naevus. The risk-benefit ratio should be assessed prior to consideration of this molecule. In this narrative review, we have attempted to present a summary of the evidence of using tofacitinib (oral and topical) in paediatric dermatoses.

Topics: Alopecia Areata; Child; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles

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.. 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.. 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.

Topics: Alopecia; Alopecia Areata; Child; Female; Humans; Male; Piperidines; Pyrimidines

Tofacitinib, a potent JAK inhibitor, has gained increasing interest, in recent years, among dermatologists for the management of refractory alopecia areata. Despite a growing number of studies on its safety and efficacy, there is still a lack of clarity, especially in the pediatric population, in treatment considerations such as proper dosage, treatment duration, side-effect profile, and therapeutic strategies to guide clinicians.. Multiple databases were systematically searched. Following the PRISMA diagram, of a pool of 601 papers, seven met a checklist of inclusion criteria. These were observational studies including a total of 59 patients from four to 19 years of age.. Results of this review suggest that tofacitinib at 2.5-15 mg daily (especially 5 mg twice daily) oral formulation or 2% topical solution can be regarded as a viable alternative or adjunct to the conventional treatment options for moderate to severe forms of alopecia areata in children owing to its acceptable efficacy and side-effect profile. However, uncertainties continue to exist around treatment strategies including initial and maintenance dosages, route of administration, dose adjustments, the timing of tapering or discontinuation, and associated treatment modalities.

Topics: Alopecia Areata; Child; Humans; Piperidines; Pyrroles

Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies.. MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available.. Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions.. While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.

Topics: Alopecia Areata; Arthritis, Psoriatic; Colitis, Ulcerative; Dermatitis, Atopic; Dermatology; Humans; Off-Label Use; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Randomized Controlled Trials as Topic

Recent insights showed the possibility of using JAK inhibitors for the treatment of alopecia areata (AA). Most of the previous articles evaluated the overall efficacy of existing JAK inhibitors rather than evaluating one of them alone. Currently, the benefit and risk profile of tofacitinib for the treatment of AA is still not clear.. To estimate the safety and efficacy of tofacitinib in patients with AA based on summarizing the clinical outcomes.. The systematic review and meta-analysis was performed according to PRISMA guidelines. ROBINS-I (Risk of Bias in Non-randomized Studies-of Interventions) was used for quality assessment.. We enrolled 14 studies including six clinical trials and eight observational studies with 275 patients. The result of meta-analysis showed that tofacitinib has reasonable effectiveness in patients with AA. The pooled good/complete hair regrowth rate of tofacitinib treating patient with AA was 54.0% (95% CI: 46.3%-61.5%), and the pooled rate of partial response in patients with AA taking tofacitinib was 26.1% (20.7-32.2%). Approximately a quarter of patients had experience of relapse, most of which was reported due to discontinuation of tofacitinib. In terms of toxicity, reported adverse effects included only mild symptoms. Upper respiratory infection, headache and acne were the most common adverse events.. Tofacitinib seems to be a promising drug for the treatment of AA with only mild adverse effects. More thorough larger sized randomized clinical trials are required to further assess the safety and clinical efficacy of tofacitinib for the treatment of AA.

Topics: Alopecia Areata; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Risk Assessment

Alopecia areata is a common autoimmune condition that disproportionately affects children and can significantly hinder quality of life. Few safe and effective therapies are available for the treatment of severely affected pediatric patients. JAK inhibitors have been recently established as an effective and well-tolerated therapy in adults, but there are limited data regarding the use of JAK inhibitors to treat alopecia areata in children. Here, we review the available literature regarding the use of JAK inhibitors in children in dermatology and across other medical disciplines.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Alopecia Areata; Arthritis, Juvenile; Child; Child, Preschool; Humans; Janus Kinase Inhibitors; Neoplasms; Nitriles; Piperidines; Pyrazoles; Pyrimidines

The treatment of hair loss is a challenge for all dermatologists. New medications are needed due to lack of efficacy of many treatments or their side-effect profile. This article discusses the most recent literature updates on the use of retinoids in frontal fibrosing alopecia, platelet-rich plasma in androgenetic alopecia, and JAK inhibitors in alopecia areata.

Topics: 5-alpha Reductase Inhibitors; Alopecia; Alopecia Areata; Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Platelet-Rich Plasma; Purines; Pyrazoles; Pyrimidines; Pyrroles; Retinoids; Sulfonamides

Alopecia areata (AA) is a relatively common disease, but no satisfactory treatment has yet been developed. Recently, research progress has been made in the pathogenesis of AA, revealing that autoreactive cytotoxic T cells are important and that the Janus kinase (JAK) pathway is involved. Therefore, the potential of JAK inhibitors as therapeutic agents for AA is attracting attention. Several single-arm clinical trials and retrospective studies demonstrated that oral JAK inhibitors are effective and tolerable treatments for moderate to severe AA. Although JAK inhibitors are emerging as an innovative treatment for AA, further placebo-controlled clinical trials are required to confirm their efficacy and long-term safety.

Topics: Administration, Oral; Alopecia Areata; Azetidines; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Janus Kinase Inhibitors; Janus Kinases; Middle Aged; Nitriles; Piperidines; Purines; Pyrazoles; Pyrimidines; Pyrroles; Signal Transduction; Sulfonamides; T-Lymphocytes, Cytotoxic; Treatment Outcome

Alopecia areata (AA) is an autoimmune disease affecting people of all ages. There is currently no cure for AA, and a highly efficacious therapy for severe AA has been elusive. Recently, scientific advances have identified the Janus kinase pathway as a target for treatment. Both Janus kinase inhibitors approved by the US Food and Drug Administration, tofacitinib and ruxolitinib, have shown promise in open-label clinical trials. This review summarizes the results of long-term use of tofacitinib in severe AA.

Topics: Administration, Topical; Adolescent; Adult; Algorithms; Alopecia Areata; Autoimmune Diseases; Clinical Trials as Topic; Female; Humans; Janus Kinase Inhibitors; Male; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is a common hair loss disorder worldwide with characteristic exclamation mark hairs. Although AA is self-limited, it can last for several months or even years in some patients. Currently, there is no US Food and Drug Administration-approved treatment for AA. Many off-label treatments are available but with limited efficacy. Through a better understanding of molecular biology, many targeted therapies have emerged as new alternatives for various autoimmune diseases. Various janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins form signaling pathways, which transmit extracellular cytokine signals to the nucleus and induce DNA transcriptions. By inhibiting JAK, T-cell-mediated inflammatory responses are suppressed. Increasing evidence suggests that JAK inhibitors (JAKis) are effective in the treatment of many autoimmune diseases, including AA. Among these, several studies on tofacitinib, ruxolitinib, and baricitinib in AA had been published, demonstrating promising outcomes of these agents. Unlike oral formulations, efficacy of topical forms of tofacitinib and ruxolitinib reported in these studies is still unsatisfactory and requires improvement. This review aims to summarize evidence of the efficacy and safety of JAKis in the treatment of AA.

Topics: Alopecia Areata; Animals; Humans; Janus Kinase Inhibitors; Janus Kinases; Piperidines; Pyrimidines; Pyrroles

KD is an 8 year-old male patient who presented to our clinic in December 2016 with a history of patchy hair loss for many months duration that was worsening. KD's past medical history was notable for atopic dermatitis, and a positive family history of autoimmune thyroid disease. Upon examination he had well circumscribed areas of hair loss throughout his scalp, with exclamation mark hairs seen on dermoscopy. Eyebrows and eyelashes were intact, no epidermal changes of scale or erythema were noted on the scalp and no palpable lymph nodes were present. He was diagnosed with alopecia areata at this time and was treated with Clobetasol 0.05% solution QHS as well as Kenalog 2.5 mg/ml injections to the areas of hair loss. Patient followed up two months later with worsening of his alopecia at a rapid pace, presenting now with hair loss of the entire scalp and loss of the eyebrows. He was diagnosed with progression to alopecia universalis at that time, with a corresponding SALT (Severity of Alopecia Tool) score of 100. Both KD and his mother stated the hair loss was causing much distress in the patient's life both at school and at home. After a thorough discussion of treatment alternatives to include continued topical high dose steroids, intralesional injections, high dose oral methylprednisolone, topical irritation with anthralin, topical immunotherapy with diphenylcyclopropenone (DPCP) or squaric acid dibutylester (SADBE) and systemic immunosuppressives, both the mother, patient and clinician agreed to try tofacitinib 5 mg twice daily with continued usage of topical steroids. Patient and his family was counseled about support groups, and local meetings to ease the mental distress associated with this condition. After baseline labs were obtained and reported within normal limits, to include CBC, CMP, thyroid studies, lipids and Quanitferon gold, KD was started on tofacitinib 5 mg BID. Labs were repeated one month later, and 3 months ongoing thereafter. At KD's 3 month follow up, after starting tofacitinib 5 mg twice daily, KD showed complete regrowth of the eyebrows with minimal hair growth of the posterior occiput (Figure 1 a-d). At KD's 6 month follow up he had 100% regrowth of eyebrows and complete scalp regrowth, resulting in a SALT score of 0 (Figure 2). KD reported no side effects until month 6, after full hair regrowth, when patient started to report mild headaches. Drug holiday was offered but the patients family chose to discontinue treatment at this tim

Topics: Alopecia Areata; Child; Drug Therapy, Combination; Follow-Up Studies; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Steroids; Treatment Outcome

Janus kinase inhibitors are emerging treatment alternatives in various immune-mediated diseases including alopecia universalis. Herein, we report a patient with psoriasis and alopecia universalis in whom treatment with tofacitinib led to remission of psoriasis without improvement in alopecia universalis. Despite the promising potential in alopecia areata treatment, research evaluating the efficacy of different Janus kinase inhibitors and possible prognostic factors related with a more favorable response are warranted.

Topics: Alopecia Areata; Humans; Janus Kinase Inhibitors; Male; Piperidines; Psoriasis; Pyrimidines; Pyrroles; Treatment Failure; Young Adult

Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are US FDA approved drugs in this family for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. The JAK/STAT signaling pathway and its involvement in skin diseases are overviewed in this study. We also review clinical studies of JAK inhibitors in field of dermatology, including psoriasis, atopic dermatitis, alopecia areata and vitiligo. Although the available evidence shows promising results, it is still too early to draw a firm conclusion about the place of these drugs in dermatological treatment.

Topics: Alopecia Areata; Azetidines; Dermatitis, Atopic; Humans; Janus Kinase Inhibitors; Janus Kinases; Nitriles; Piperidines; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Skin Diseases; Sulfonamides; Vitiligo

Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology.. We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included.. Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata.. JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio.

Topics: Administration, Oral; Alopecia Areata; Dermatitis, Atopic; Humans; Janus Kinases; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Signal Transduction; Skin Diseases; Vitiligo

New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase-signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

Topics: Alopecia Areata; Anti-Inflammatory Agents; Azetidines; Clinical Trials as Topic; Dermatitis, Atopic; Dermatologic Agents; Humans; Janus Kinases; Molecular Targeted Therapy; Nitriles; Piperidines; Protein Kinase Inhibitors; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Signal Transduction; Skin Diseases; Sulfonamides; Vitiligo

Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions.. Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases.. This is a systematic review of PubMed and ClinicalTrials.gov.. One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections.. It was not possible to perform a meta-analysis of the results.. This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.

Topics: Alopecia Areata; Anti-Inflammatory Agents; Antineoplastic Agents; Azetidines; Dermatologic Agents; Drug Eruptions; Humans; Janus Kinases; Molecular Targeted Therapy; Nitriles; Piperidines; Protein Kinase Inhibitors; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Signal Transduction; Skin Diseases; Sulfonamides

IL-15 has a pivotal role in life and death of natural killer (NK) and CD8 memory T cells. IL-15 signals through a heterotrimeric receptor involving the common gamma chain (γc) shared with IL-2, IL-4, IL-7, IL-9, and IL-21, IL-2/IL-15 receptor β (IL-15Rβ) shared with IL-2 and a private IL-15Rα subunit. IFN- or CD40 ligand-stimulated dendritic cells coordinately express IL-15 and IL-15Rα. Cell surface IL-15Rα presents IL-15 in trans to cells that express IL-2/IL-15Rβ and γc. IL-15 is being used to treat patients with metastatic malignancy. However, IL-15 is an inflammatory cytokine involved in immunological memory including that to self, thereby playing a role in autoimmune diseases. These insights provide the scientific basis for clinical strategies directed toward diminishing IL-15 action. Dysregulated IL-15 expression was demonstrated in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, celiac disease, and alopecia areata. The monoclonal antibody Hu-Mik-β-1 targets the cytokine receptor subunit IL-2/IL-15Rβ (CD122), blocks IL-15 transpresentation, and is being used in clinical trials in patients with autoimmune diseases. In parallel, clinical trials have been initiated involving the Jak2/3 (Janus kinase-2/3) inhibitor tofacitinib and Jak1/2 inhibitor ruxolitinib to block IL-15 signaling.

Topics: Alopecia Areata; Animals; Antibodies, Monoclonal; Autoimmune Diseases; Humans; Interleukin-15; Leukemia-Lymphoma, Adult T-Cell; Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Receptors, Interleukin-15; Signal Transduction

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.

Topics: Alopecia Areata; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome

Alopecia areata (AA) is a common autoimmune disorder characterized by patchy hair loss. There are many treatments available for AA. However, treatments of severe forms of AA are not satisfactory. Recently, oral Janus kinase (JAK) inhibitors were found to be effective for the treatment of severe AA variants.. The aim of this work was to evaluate and compare the efficacy, side effects, and durability of two oral JAK inhibitor medications (ruxolitinib and tofacitinib) in the treatment of severe AA.. This study included 75 patients with AA with more than 30% scalp hair loss, alopecia totalis, and alopecia universalis randomized into 2 groups. The first group (n = 38) received ruxolitinib 20 mg twice daily, and the second group (n = 37) received oral tofacitinib 5 mg twice daily. The treatment continued for 6 months followed by 3 months of follow-up off therapy. Efficacy of treatment was assessed by monitoring the change in the Severity of Alopecia Tool (SALT) score.. Both tofacitinib and ruxolitinib induced remarkable hair regrowth, with a mean change in SALT score of 93.8 ± 3.25 in the ruxolitinib group and 95.2 ± 2.69 in the tofacitinib group. However, the ruxolitinib group showed a shorter duration for initial hair regrowth. There was no statistically significant difference between the groups regarding hair regrowth at the end of the 6-month treatment and relapse rate at the end of the 3-month follow-up. Around two thirds of cases experienced relapse. Both drugs were well tolerated, with no reported serious adverse effects.. Both ruxolitinib and tofacitinib could be considered effective and well-tolerated treatments for extensive AA.

Topics: Administration, Oral; Adolescent; Adult; Alopecia; Alopecia Areata; Female; Hair; Humans; Janus Kinase Inhibitors; Male; Middle Aged; Nitriles; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Recurrence; Severity of Illness Index; Time Factors; Young Adult

Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.

Topics: Adult; Alopecia Areata; Autoimmune Diseases; Biopsy; Dose-Response Relationship, Drug; Female; Gene Expression Profiling; Hair Follicle; Humans; Janus Kinase Inhibitors; Janus Kinases; Male; Middle Aged; Nitriles; Photography; Pilot Projects; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Severity of Illness Index; Treatment Outcome; Young Adult

Alopecia areata is an autoimmune disease involving the hair follicle with a chronic, relapsing course. Tofacitinib is Janus kinase inhibitor approved for treatment of rheumatoid arthritis that has been shown to be effective in treatment of alopecia areata. We present a case series of 11 patients with severe alopecia areata on longstanding, regular to high dose oral tofacitinib with marked hair regrowth. Additionally, we present a case of moderate to severe alopecia areata successfully treated with topical tofacitinib cream. J Drugs Dermatol. 2018;17(7):800-803.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Alopecia Areata; Female; Follow-Up Studies; Hair Follicle; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome; Young Adult

Topics: Alopecia; Alopecia Areata; COVID-19; Humans; Piperidines; Pyrroles

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.. 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.. 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.. Tofacitinib is an effective and well-tolerated treatment for severe AA and exhibits a good safety profile.

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Prospective Studies; Pyrimidines; Pyrroles; Saudi Arabia; Treatment Outcome

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.. To summarize the clinical outcomes of pediatric patients with AA treated with oral tofacitinib at the University of Colorado Hospital Dermatology Clinic.. 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.. 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.. Oral tofacitinib was clinically effective in the majority our of patients and well tolerated.

Topics: Adolescent; Alopecia; Alopecia Areata; Child; Female; Humans; Male; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies; Treatment Outcome

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.

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies

Topics: Alopecia Areata; Child; Follow-Up Studies; Humans; Piperidines; Pyrimidines

Dermatomyositis (DM) and alopecia areata are two diseases characterised by aberrant interferon signalling. While patchy alopecia of the scalp is a known feature of DM, alopecia universalis, which involves hair loss over the entire body, has rarely been reported in conjunction with DM. Herein, we report the case of a 30-year-old female with DM who developed refractory cutaneous disease and alopecia universalis that were successfully treated with tofacitinib. This could suggest that concomitant severe alopecia and refractory cutaneous DM may reflect a strong baseline interferon gene signature that may predict responsiveness to janus kinase inhibitors.

Topics: Adult; Alopecia; Alopecia Areata; Dermatomyositis; Female; Humans; Interferons; Piperidines; Pyrimidines; Pyrroles

Topics: Alopecia Areata; Humans; Multiple Sclerosis; Piperidines; Protein Kinase Inhibitors; Pyrimidines

Topics: Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

Alopecia universalis (AU) is an autoimmune disorder characterized by non-scarring hair loss in the scalp, eyebrows, beard, and nearly the entire body, negatively affecting patient prognosis. Available treatments are usually unsatisfactory. The autoimmune attacks of hair follicles induced by CD8+ T cells and the collapse of hair follicle immune privilege are believed to be the leading causes of AU. Additionally, interferon (IFN)-γ plays an important role in triggering the collapse of hair follicle immune privilege and impairing hair follicle stem cells. Furthermore, the upregulation of Janus kinase (JAK)3 and phospho-signal transducer and activator of transcription (pSTAT)3/STAT1 in alopecia areata patients suggest that JAK inhibitors can be a potentially promising choice for AU patients for the reason that JAK inhibitors can interfere with JAK-STAT signaling pathways and inhibit IFN-γ. Herein, we report a case of AU successfully treated with tofacitinib. However, this beneficial response in the patient was accompanied by a remarkable increase in peripheral blood cytokine levels during tofacitinib treatment.

Topics: Alopecia; Alopecia Areata; Cytokines; Humans; Janus Kinase Inhibitors; Piperidines; Pyrimidines

Topics: Alopecia; Alopecia Areata; Child, Preschool; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Alopecia Areata; Eyebrows; Humans; Piperidines; Pyrimidines

Alopecia areata (AA) is a psychologically distressing disorder for which few reliable treatments exist. Although oral tofacitinib has demonstrated efficacy in treating AA, it is not approved by the Food and Drug Administration (FDA) for this indication. To investigate and identify the challenges associated with securing insurance approval for oral tofacitinib for AA. We conducted a retrospective review of patient records from two academic medical centers to identify patients with AA in whom insurance approval was sought for oral tofacitinib from 2015-2019. We recorded information on prior authorization (PA) submissions, appeals, and peer-to-peer reviews. We noted whether patients were documented to experience negative impact on mood/QOL or suicidal ideation (SI) due to their disease. We identified 37 patients in whom insurance approval was sought for oral tofacitinib for the treatment of AA. PAs were initially denied for 36/37 (97%) patients. The most commonly cited reason for denial was "tofacitinib not covered for AA/off-label medication use" (n = 26/36; 72%). 26/37 (70%) patients ultimately failed to obtain coverage. Of the 11 (30%) patients who obtained coverage, 10 (91%) were privately insured, 0 (0%) had Medicare and 1 (9%) had Medicaid. 13 patients (34%) experienced documented diminished QOL/mood (including SI) due to their disease burden; 6/13 (46%) of these patients eventually secured insurance approval. Lack of FDA approval of oral tofacitinib for the treatment of AA creates challenges in caring for patients with this disease. Policymakers should consider the negative implications lack of FDA approval may have for patients with recalcitrant dermatologic conditions.

Topics: Aged; Alopecia Areata; Humans; Insurance; Medicare; Piperidines; Pyrimidines; Pyrroles; Quality of Life; Retrospective Studies; United States

Topics: Alopecia; Alopecia Areata; Child; Humans; Piperidines; Pyrimidines; Pyrroles; Young Adult

Topics: Administration, Topical; Alopecia; Alopecia Areata; Humans; Minoxidil; Piperidines; Pyrimidines

Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs.. In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity.. We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5 mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay.. A moderate correlation was found between SALT scores and serum granulysin level at baseline (r = .378, P = .019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P = .004, Z = 2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P = .001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P = .001).. Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.

Topics: Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2 × 5 mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.. Wir präsentieren den Fall einer 46-jährigen Patientin, die an einer entzündlich aktiven Alopecia areata universalis leidet. Nach frustranem Einsatz von topischen und systemischen Glukokortikoiden, einer Creme-PUVA-Therapie und Dithranol in aufsteigender Dosierung wurde die Patientin mit 2‑mal 5 mg pro Tag Tofacitinib per os behandelt. Nach ca. 4 bis 6 Monaten zeigte die Patientin ein Haarwachstum, das bei guter Verträglichkeit bis zum 18. Therapiemonat zur vollständigen Wiederbehaarung geführt hat. Der Fall zeigt eindrucksvoll, dass die Off-label-Anwendung von Tofacitinib eine potenzielle therapeutische Option in der Indikation Alopecia areata darstellen kann.

Topics: Alopecia; Alopecia Areata; Female; Humans; Middle Aged; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is an autoimmune nonscarring alopecic disorder, which presents with varying amounts of hair loss, ranging from focal patchy loss to entire scalp and body hair loss. Treatment of AA is a challenging issue within dermatology practice. Although many treatment options are present, response to medications remains unsatisfactory, especially in severe and recalcitrant cases. In this study, we present a case of treatment-resistant AU, which was successfully treated by the combination of tofacitinib and oral minoxidil.

Topics: Alopecia; Alopecia Areata; Humans; Minoxidil; Piperidines; Pyrimidines; Pyrroles

Alopecia areata (AA) is an autoimmune hair loss condition that affects people of all ages. Early age of onset and prolonged disease duration indicate poor prognosis. Janus kinase inhibitors are being investigated in phase 3 clinical trials in adolescents and adults with AA OBJECTIVE: To evaluate the use of oral tofacitinib in pre-adolescent patients with AA.. A retrospective review of case records of all pre-adolescent patients with AA treated with oral tofacitinib in a single center between 2018 and 2019.. Fourteen patients were identified, aged 7 to 11 years. Nine patients experienced clinically significant improvement in their SALT (Severity of Alopecia Tool) score. Three patients achieved complete remission (SALT score of 0), seven (63.6%) achieved over 50% improvement in SALT score from baseline. One patient had no change from baseline, another experienced additional hair loss. After an average of 9 months of treatment, the median SALT score improvement was 67.7%. The improvement was similar in patients with baseline SALT scores greater than 50 and those with baseline SALT scores below 10. Adverse events were mild.. The retrospective nature of the data, small sample size, lack of a control group, referral bias to a specialist hair center, and concomitant use of other medications including oral minoxidil in all patients.. There is a role for tofacitinib as a systemic therapy in AA and this should be further evaluated in prospective clinical trials in pre-adolescents.

Topics: Adolescent; Adult; Alopecia; Alopecia Areata; Child; Humans; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies

Tofacitinib is a Janus Kinase 3 inhibitor that is used in the treatment of alopecia areata. We recommended our alopecia areata patients to discontinue their tofacitinib treatment during the COVID-19 pandemic for an average of 80 days. We aimed to evaluate the drug use and the SARS-CoV-2 infection status of alopecia areata patients; and the relationships of recurrence to age, gender, treatment duration, and tofacitinib discontinuation. One-hundred and ninety-one (61.4%) patients were off the drug and 120 (38.6%) were on therapy during the pandemic. The relationship between drug discontinuation due to the COVID-19 pandemic and recurrence was statistically significant (P < .001). Statistically significant relationships of age (P = .013) and treatment duration (P < .001) to recurrence were also found. The change in the SALT score differed between the patients on therapy and off therapy during the pandemic (P < .001). A significant negative correlation was found between the change in the SALT score and treatment duration: the spearman correlation test P = .018. We concluded that the patients may continue to the tofacitinib therapy during the rest of the COVID-19 pandemic if the benefit outweighed the risk.

Topics: Alopecia Areata; COVID-19; Humans; Pandemics; Piperidines; Pyrimidines; SARS-CoV-2

Topics: Alopecia Areata; Colitis, Ulcerative; Humans; Piperidines; Pyoderma Gangrenosum; Pyrimidines

Alopecia areata (AA) and generalized form, universalis (AU) are common causes of noncicatricial alopecia, targeting anagen hair follicles. A dominant interferon-gamma transcriptional signaling and cytotoxic T lymphocytes were accused as the main drivers of disease pathogenesis. Tofacitinib is a Janus kinase inhibitor that has been proven to interfere with the positive feedback loop between the follicular cell and the cytotoxic T lymphocytes in AA. There is an increasing number of studies reporting success with tofacitinib in AA.. We aimed to assess oral tofacitinib's safety and efficacy in 13 recalcitrant AA and AU patients.. This is a retrospective pilot study performed between 2017 and 2020. The demographic features and the treatment responses were evaluated with Severity of Alopecia Tool score changes.. Thirteen recalcitrant alopecia areata patients (3 AA, 10 AU), aged between 17 and 49, were included in the study. The treatment duration was 3-15 months. All three AA patients responded well; however, the therapy was unsuccessful in five of ten AU patients. Relapse was observed in one of the AA and three of the AU responders. Acneiform lesions and elevation of transaminases were the major side effects.. Tofacitinib seems to be more promising and thriving in the treatment of AA than AU. Starting the therapy earlier can bring more successful results. Unfortunately, even in the cases that fully respond to treatment, relapse can be observed after discontinuation of the treatment. It is essential to inform patients about this situation in reducing the frustrations that may occur later.

Topics: Adolescent; Adult; Alopecia Areata; Humans; Middle Aged; Pilot Projects; Piperidines; Pyrimidines; Retrospective Studies; Young Adult

Topics: Alopecia Areata; COVID-19; Humans; Piperidines; Pyrimidines

Topics: Alopecia; Alopecia Areata; Child; Humans; Piperidines; Pyrimidines; Pyrroles

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) are key intracellular mediators in the signal transduction of many cytokines and growth factors. Common γ chain cytokines and interferon-γ that use the JAK/STAT pathway to induce biological responses have been implicated in the pathogenesis of alopecia areata (AA), a T cell-mediated autoimmune disease of the hair follicle. We previously showed that therapeutic targeting of JAK/STAT pathways using the first-generation JAK1/2 inhibitor, ruxolitinib, and the pan-JAK inhibitor, tofacitinib, was highly effective in the treatment of human AA, as well as prevention and reversal of AA in the C3H/HeJ mouse model. To better define the role of individual JAKs in the pathogenesis of AA, in this study, we tested and compared the efficacy of several next-generation JAK-selective inhibitors in the C3H/HeJ mouse model of AA, using both systemic and topical delivery. We found that JAK1-selective inhibitors as well as JAK3-selective inhibitors robustly induced hair regrowth and decreased AA-associated inflammation, whereas several JAK2-selective inhibitors failed to restore hair growth in treated C3H/HeJ mice with AA. Unlike JAK1, which is broadly expressed in many tissues, JAK3 expression is largely restricted to hematopoietic cells. Our study demonstrates inhibiting JAK3 signaling is sufficient to prevent and reverse disease in the preclinical model of AA.

Topics: Administration, Topical; Alopecia Areata; Animals; Azetidines; CD8-Positive T-Lymphocytes; Cytokines; Isonicotinic Acids; Janus Kinase 1; Janus Kinase 2; Janus Kinase 3; Macrophages; Mice, Inbred C3H; Nitriles; NK Cell Lectin-Like Receptor Subfamily K; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Pyrimidines; Pyrroles; Triazoles

Topics: Administration, Topical; Alopecia; Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

The Janus kinases (JAKs) are intracellular tyrosine kinases involved in a broad variety of inflammatory cascades participating in the pathogenesis of systemic lupus erythematosus (SLE). Diffuse non-scarring alopecia is one of the most frequent cutaneous manifestations in SLE, resulting in devastating psychosocial consequences. Although recent studies have shown promising outcomes of the JAK inhibitors in SLE treatment, the efficacy of tofacitinib in diffuse non-scarring alopecia due to SLE has never been reported. Here we present a 29-year-old SLE patient with a 10-year history of refractory severe diffuse non-scarring alopecia who experienced dramatic hair regrowth with tofacitinib. Furthermore, we have made a systematic review regarding the potential effectiveness of tofacitinib in systemic and cutaneous lupus erythematosus. To the best of our knowledge, this is the first case study depicting an SLE patient with refractory alopecia who experienced impressive hair regrowth with the JAK1/3 inhibitor tofacitinib therapy, which contributes to expanding the field of possible uses of tofacitinib in SLE patients with difficult-to-treat cutaneous involvement, including severe alopecia.

Topics: Adult; Alopecia Areata; Chronic Disease; Female; Humans; Lupus Erythematosus, Systemic; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Recurrence; Treatment Outcome

Topics: Administration, Oral; Adult; Aged; Alopecia Areata; Cheek; Chin; Humans; Janus Kinases; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Scalp; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Female; Health Facilities; Humans; Insurance Coverage; Male; Middle Aged; Piperidines; Pyrimidines; Retrospective Studies; Universities

A 40-year-old woman (case 1) visited the hospital complaining of diarrhea and was diagnosed with ulcerative colitis (UC). She was administered 5-aminosalicylic acid (5-ASA), but developed intolerance. Prednisolone (PSL) was administered, and her symptoms improved. However, alopecia areata developed as the PSL was tapered, and her UC relapsed. Adalimumab, Infliximab (IFX), and golimumab were used, but all showed insufficient efficacy. Therefore, we started tofacitinib (TOF). Her bloody stools and diarrhea improved 3 days after TOF administration, and clinical remission occurred on day 14. Her alopecia areata improved 14 days after starting TOF and improved completely during TOF maintenance therapy. A 19-year-old man (case 2) had developed alopecia areata at 10 years old and was diagnosed with UC at 17 years old. He achieved sustained remission with IFX, but then stopped IFX to receive a live vaccination. His UC relapsed 4 months later, immediately after the live vaccine was administered. Vedolizumab was administered, but was ineffective, as was re-administration of IFX. TOF was administered, and his clinical symptoms improved 7 days later. He achieved clinical remission on day 20. In addition, his hair began to regrow 14 days after starting TOF.

Topics: Adult; Alopecia Areata; Colitis, Ulcerative; Female; Humans; Infliximab; Male; Piperidines; Pyrimidines; Pyrroles; Young Adult

Topics: Alopecia Areata; Animals; Mice; Piperidines; Pyrimidines; Pyrroles; Thalidomide

Alopecia areata (AA) is a common disease that results in nonscarring hair loss. Recently, tofacitinib (TOFA) has been a novel promising therapy for AA. The aim of this study is to determine the efficacy of oral TOFA treatment for alopecia areata (AA), and alopecia universalis (AU). Data of nine patients treated with oral TOFA with either AA or AU were retrospectively evaluated. Treatment outcome, disease severity, and therapeutic response were evaluated by Severity of Alopecia Tool (SALT) scores along with regular photographic surveillance done at third and sixth months. Treatment response was established on four categories: complete response (90% change in latest SALT score), intermediate response (51-90% change), moderate response (6-50% change), and nonresponse (<5% change). Nine patients aged 13-33 years were reviewed. Four patients (44.4%) did not respond to oral TOFA therapy, three patients (33.3%) were moderate responders, 1 (11.1%) was intermediate responder, and 1 (11.1%) was complete responder at the end of 6 months. The clinical response rate (those who achieved ≥5-100% change in SALT score) was 41.4% for all patients. Most of the patients who responded to TOFA had AA instead of AU. Adverse effects were mild. The clinical response rate of TOFA seems reasonable and TOFA was well-tolerated in this cohort. However, to truly evaluate efficacy, future studies are needed to assess the efficacy, adverse effects, and durability of treatment with TOFA in randomized controlled trials.

Topics: Administration, Oral; Adolescent; Adult; Alopecia; Alopecia Areata; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Cost Savings; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Administration, Oral; Age Factors; Alopecia Areata; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Janus Kinase Inhibitors; Male; Piperidines; Prospective Studies; Pyrimidines; Pyrroles; Quality of Life; Risk Assessment; Sampling Studies; Treatment Outcome

Topics: Adolescent; Adult; Alopecia Areata; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hair; Humans; Male; Middle Aged; Nitriles; Patient Satisfaction; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Retrospective Studies; Sampling Studies; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Dermatitis, Contact; Hair; Humans; Male; Piperidines; Pyrimidines; Pyrroles; Silicone Gels; Treatment Outcome

Topics: Administration, Topical; Adult; Alopecia Areata; Cohort Studies; Eyebrows; Eyelashes; Female; Follow-Up Studies; Humans; Male; Middle Aged; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies; Risk Assessment; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Female; Humans; Janus Kinases; Middle Aged; Nitriles; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Pyrroles; Recurrence; Withholding Treatment

Topics: Alopecia; Alopecia Areata; Child, Preschool; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Severity of Illness Index

Topics: Adolescent; Adult; Alopecia Areata; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome; Young Adult

Currently, no standardized treatment for severe alopecia areata (AA) exists. Numerous successful cases of the use of tofacitinib have been reported in the world literature, but not in Mexico. Four Mexican adolescents with severe AA treated with oral tofacitinib are reported in the present work.. Series of cases of adolescents with severe AA treated with oral tofacitinib. The severity of alopecia tool was used to determine the response to treatment.. Four patients from 13 to 19 years old, were included. In all cases, hair growth was observed, and the alopecia severity decreased after the treatment with tofacitinib. In two patients, an intermediate response (from 51 to 90%) was observed; in the other, a moderate response (from 6 to 50%) was observed, without serious adverse effects. The limitations of the study were the small sample size and the retrospective nature of data collection.. Tofacitinib showed to be a good treatment alternative for AA, total and universal, refractory to other therapies.. Actualmente no existe un tratamiento estandarizado para la alopecia areata (AA) grave. Se han reportado numerosos casos exitosos del uso de tofacitinib; sin embargo, no existen publicaciones en México. En este trabajo se reportan cuatro casos de pacientes mexicanos con AA grave tratados con tofacitinib oral.. Serie de casos de adolescentes con alopecia grave tratados con tofacitinib oral. Para determinar la respuesta al tratamiento se utilizó la Escala de gravedad de alopecia (Severity of alopecia tool).. Se incluyeron cuatro pacientes de entre 13 y 19 años con AA. En todos los casos se observó crecimiento de cabello y disminución de la gravedad de la alopecia después del tratamiento con tofacitinib. En dos pacientes se observó una respuesta intermedia (del 51 al 90%), y en los otros, moderada (del 6 al 50%), sin efectos adversos serios. Las limitaciones del estudio fueron el tamaño reducido de la muestra y la naturaleza retrospectiva de la recolección de los datos.. El tofacitinib demostró ser una buena alternativa de tratamiento para la AA, total y universal, refractarias a otras terapias.

Topics: Administration, Oral; Adolescent; Alopecia Areata; Female; Humans; Male; Mexico; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Female; Hair; Humans; Male; Middle Aged; Ointments; Pilot Projects; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Young Adult

Topics: Adult; Alopecia Areata; Emotions; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Young Adult

Topics: Alopecia Areata; Humans; Piperidines; Pyrimidines; Pyrroles

A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA.. To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib.. This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months.. Fifteen patients had nail involvement and demonstrated more severe hair loss than those without nail involvement (p = .040). However, there was no significant difference in hair regrowth between two groups. Of 15 patients with nail involvement, 11 (73.3%) showed improvement regardless of type of nail change; the first improvement was observed at a median of 5 months (range, 1-11) after administration. Nail improvement was associated with neither initial severity of hair loss nor hair response to tofacitinib. Nail improvement tended to occur later than hair regrowth.. Oral tofacitinib monotherapy improves nail involvement associated with AA. Nail involvement is not a poor prognosis factor in hair regrowth with tofacitinib treatment and there is no evident relationship between nail and hair responses.

Topics: Administration, Oral; Adult; Alopecia Areata; Female; Humans; Male; Middle Aged; Nail Diseases; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies

Topics: Administration, Topical; Adolescent; Alopecia; Alopecia Areata; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hair; Humans; Male; Pediatrics; Piperidines; Pyrimidines; Pyrroles; Sampling Studies; Treatment Outcome

Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells specifically target growing hair follicles. We used high-throughput TCR sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain insight into pathogenic T cell populations and their dynamics, which revealed clonal CD8+ T cell expansions in lesional skin. In the C3H/HeJ model, we observed interindividual sharing of TCRβ chain protein sequences, which strongly supports a model of antigenic drive in AA. The overlap between the lesional TCR repertoire and a population of CD8+NKG2D+ T cells in skin-draining lymph nodes identified this subset as pathogenic effectors. In AA patients, treatment with the oral JAK inhibitor tofacitinib resulted in a decrease in clonally expanded CD8+ T cells in the scalp but also revealed that many expanded lesional T cell clones do not completely disappear from either skin or blood during treatment with tofacitinib, which may explain in part the relapse of disease after stopping treatment.

Topics: Adolescent; Adult; Alopecia Areata; Animals; Autoimmune Diseases; CD8-Positive T-Lymphocytes; Disease Models, Animal; Female; Follow-Up Studies; Hair Follicle; High-Throughput Nucleotide Sequencing; Humans; Lymph Nodes; Male; Mice; Mice, Inbred C3H; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K; Pilot Projects; Piperidines; Pyrimidines; Pyrroles; Receptors, Antigen, T-Cell; Scalp; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Female; Follow-Up Studies; Hair; Humans; Male; Middle Aged; Piperidines; Polyps; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Scalp; Treatment Outcome; Young Adult

Topics: Administration, Cutaneous; Adolescent; Alopecia Areata; Child, Preschool; Female; Humans; Janus Kinases; Male; Nitriles; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Pyrroles; Skin Cream

Topics: Administration, Oral; Adolescent; Adult; Alopecia Areata; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Republic of Korea; Retrospective Studies; Severity of Illness Index; Young Adult

Topics: Adult; Alopecia Areata; Dermatitis, Atopic; Humans; Janus Kinase Inhibitors; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Th2 Cells; Treatment Outcome; Vitiligo

Topics: Adolescent; Alopecia; Alopecia Areata; Arthritis, Psoriatic; Female; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retreatment

There are no reliably effective therapies for alopecia areata (AA).. We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA.. We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems.. Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild.. Limitations include the retrospective nature of the data, small sample size, and lack of a control group.. Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials.

Topics: Adolescent; Alopecia; Alopecia Areata; Female; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA.. We sought to evaluate the safety and efficacy of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of patients over an extended period of time.. This is a retrospective study of patients age 18 years or older with AA with at least 40% scalp hair loss treated with tofacitinib. The primary end point was the percent change in Severity of Alopecia Tool (SALT) score during treatment.. Ninety patients met inclusion criteria. Of 65 potential responders to therapy, defined as those with alopecia totalis or alopecia universalis with duration of current episode of disease of 10 years or less or alopecia areata, 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in SALT score over 4 to 18 months of treatment. Patients with AA experienced a higher percent change in SALT score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events.. The retrospective nature of the data, the relatively small number of patients, and lack of a control group are limitations.. Tofacitinib should be considered for the treatment of severe AA, alopecia totalis, and alopecia universalis; tofacitinib dose response will be better defined by randomized controlled trials.

Topics: Adolescent; Adult; Aged; Alopecia; Alopecia Areata; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Adult; Alopecia Areata; Biomarkers; Female; Humans; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Skin

Alopecia areata (AA) is an autoimmune disease characterized by hair loss mediated by CD8. This was a 2-center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome.. Of 66 subjects treated, 32% experienced 50% or greater improvement in SALT score. AA and ophiasis subtypes were more responsive than AT and AU subtypes. Shorter duration of disease and histological peribulbar inflammation on pretreatment scalp biopsies were associated with improvement in SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse events were limited to grade I and II infections. An AA responsiveness to JAK/STAT inhibitors score was developed to segregate responders and nonresponders, and the previously developed AA disease activity index score tracked response to treatment.. At the dose and duration studied, tofacitinib is a safe and effective treatment for severe AA, though it does not result in a durable response. Transcriptome changes reveal unexpected molecular complexity within the disease.. ClinicalTrials.gov NCT02197455 and NCT02312882.. This work was supported by the US Department of Veterans Affairs Office of Research and Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish Society of Medicine, the Fernström Foundation, the Locks of Love Foundation, the National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

Topics: Adult; Aged; Alopecia Areata; Female; Humans; Janus Kinase Inhibitors; Male; Middle Aged; Piperidines; Pyrimidines; Pyrroles; United States; Young Adult

Topics: Adult; Alopecia Areata; Carcinoma, Neuroendocrine; Humans; Male; Piperidines; Quinazolines; Thyroid Neoplasms

Topics: Adult; Alopecia Areata; Animals; Butyrophenones; Disease Models, Animal; Female; Histamine Antagonists; Humans; Immunotherapy; Mice; Mice, Inbred C3H; Piperidines; Remission Induction; Treatment Outcome