Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers.
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ABSTRACT:
SUBMITTER: Jabbari A
PROVIDER: S-EPMC4963264 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
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Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers.
Jabbari Ali A Nguyen Nhan N Cerise Jane E JE Ulerio Grace G de Jong Annemieke A Clynes Raphael R Christiano Angela M AM Mackay-Wiggan Julian J
Experimental dermatology 20160801 8
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Project description:IntroductionPatients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients' experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction.MethodsIn the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients' satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The prespecified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at weeks 24 and 48.ResultsAt week 24, the proportion of patients (N = 718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group versus 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at week 48 than at week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at weeks 24 (range 0.73-0.76; p < 0.05) and 48 (0.74-0.77; p < 0.05).ConclusionsPatients receiving active ritlecitinib doses reported favorable results versus placebo in satisfaction with hair growth up to week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction.
| S-EPMC11651339 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.MethodsWe have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years).ResultsClinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs.ConclusionsCurrent clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA.Trial registrationClinicalTrials.gov, NCT01673789, 21 August 2012.
| S-EPMC4417286 | biostudies-literature
Project description:BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3-6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment. RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers. CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA. TRIAL REGISTRATION. Clinicaltrials.gov NCT01950780. FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).
| S-EPMC5033756 | biostudies-literature
Project description: Not available
| S-EPMC10733080 | biostudies-literature
Project description:Alopecia areata (AA) is a chronic inflammatory disease mainly involving Th1 immunoreaction, but Th2 is also involved. A 9-year-old girl presented to our clinic with severe alopecia for 2 months and pruritus-related rashes for 8 years. She was diagnosed with AA and atopic dermatitis (AD), and the Severity of Alopecia Tool (SALT) score was 98. She used a 0.05% halometasone cream (occlusive dressing) topically applied overnight (6 days weekly) for 10 months. After 2 months of treatment, she had regrowth of both black and white hair. However, relapse occurred and she gradually lost all black terminal hair, but white terminal hair remained, with a SALT score of 70. Continuous topical occlusion resulted in white hair regrowth with a SALT score of 20 at the end of month 10. Dupilumab was initially prescribed as a 600-mg subcutaneous injection and maintained at 300 mg every 4 weeks thereafter. Hair repigmentation (10% of whole hair density) started, with black hair shaft appearing at the proximal end in parietal-occipital and occipital areas after three injections at week 12 of dupilumab therapy, with a SALT score of 10. After seven injections at week 28, the percentage of black hair shaft reached up to 90, and she regained her black hair and the pigmented section of hair shaft continued to grow longer at the rate of normal hair growth. Nevertheless, 4 months after termination of dupilumab therapy, the black terminal hair began to fall off, and white vellus hair gradually regrew on the scalp, with a SALT score of 80. Dupilumab induces hair regrowth and repigmentation of white terminal hair without disturbing the anagen phase of hair follicles. Therefore, melanocytes in AA may be a potential target of Th2-related factors. Persistent regrowth of white hair may be used as a signal of Th2 dominance in AA management.
| S-EPMC10403978 | biostudies-literature
Project description:Alopecia areata (AA) is nonscarring hair loss characterized by Th1 and concomitant Th2 skewing, particularly in atopic patients. Despite novel developments for adult AA, safe and effective treatments for pediatric patients remain limited. Dupilumab, with a well-studied safety profile, may have therapeutic potential for atopic pediatric AA. To evaluate the ability of dupilumab to regrow hair in pediatric AA patients. We conducted a single-center, retrospective, observational study to evaluate hair regrowth [using Severity of Alopecia Tool (SALT)] with dupilumab in 20 children with both AD and AA (age range 5-16 years, mean 10.8 years; baseline SALT range 3-100, mean 54.4). Patient demographics, atopic history, IgE and SALT scores were collected at 12wk follow-up visits, up to > 72wks, to evaluate hair regrowth. Spearman correlations with clinical data were performed. Patients showed clinical improvement over the follow-up period (range 24 to > 72wks, mean 67.6wks) with significant mean(± SD) reduction in SALT at 48wks versus baseline [20.4(± 35.1) vs 54.4(± 37.6), respectively; p < 0.01] and continued improvement up to > 72wks [2.2(± 4.9), p < 0.01]. Baseline SALT positively correlated with disease duration (r = 0.54, p < 0.01), and negatively correlated with improvement in SALT at weeks 24, 36, and 48 (|r|≥ 0.65, p < 0.01 for all comparisons). Baseline IgE positively correlated with improvement in SALT at week 36 (r > 0.60, p < 0.05). Dupilumab was well-tolerated, with no new safety concerns. These real-world data support the utility of dupilumab to safely treat pediatric AA patients, corroborating the role of Th2 skewing in children with AA and associated atopy, warranting larger clinical trials.
| S-EPMC11266226 | biostudies-literature
Project description:ObjectivesThe present analyses report integrated results from BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) on the clinical benefits of baricitinib treatment on the basis of the amount of scalp hair regrowth through 52 weeks of treatment.MethodsThis post hoc analysis was conducted with data from patients who were treated continuously for 52 weeks with baricitinib 4 mg or 2 mg. Clinical outcomes were assessed using the Severity of Alopecia Tool (SALT) and Clinician-Reported Outcome (ClinRO) for Eyebrow (EB) and Eyelash (EL) hair. Secondary measures included the Hospital Anxiety and Depression Scale and Skindex-16 adapted for alopecia areata. At week 52, patients were classified into three subgroups: SALT ≤ 20 response, intermediate response (achieved a 30% improvement from baseline (SALT30) without a SALT score ≤ 20), or nonresponse (never achieved SALT30). The criterion of SALT30 approximates a minimal clinical meaningful response to therapy.ResultsAt week 52, with baricitinib 4 mg treatment, the greatest (70%) improvement in EB and EL was observed in responders, but approximately 50% of patients with intermediate response and 20% of nonresponders experienced complete/nearly complete EB and EL regrowth. Improvement in emotional distress was directionally related to improvements in scalp hair regrowth, while impact on quality of life was proportionately greater for the responder subgroup.ConclusionsClinically meaningful regrowth in eyebrow and eyelash hair can occur in the absence of complete scalp hair regrowth after treatment with baricitinib. Emotional distress and quality of life improvement is most associated with obtaining a clinical meaningful improvement in scalp hair.Trial registration numberBRAVE-AA1, ClinicalTrials.gov number, NCT03570749, start date, 24 September 2018; BRAVE-AA2, ClinicalTrials.gov number, NCT03899259, start date, 8 July 2019.
| S-EPMC10689319 | biostudies-literature
Project description:ImportanceContact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies.ObjectiveTo summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors.Data sourceA database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric.Study selectionClinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded.Data extraction and synthesisThe following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies.Main outcomes and measuresThe main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate.ResultsForty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.Conclusions and relevanceVarious factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.
| S-EPMC6233743 | biostudies-literature
Project description:Alopecia universalis is a severe, difficult to treat variant of alopecia areata that results in loss of hair on the scalp, eyebrows, eyelashes, and extremities. Deucravacitinib, a selective TYK2 inhibitor, has been recently approved in Canada, opening the door to novel uses of the drug. We present the case of a patient known for psoriasis who developed alopecia universalis resistant to many interventions (topical minoxidil and topical, intralesional, and systemic corticosteroids). We report the first case of successful rapid hair regrowth after starting deucravacitinib, which should prompt further inquiry into the use of TYK2 inhibitors in the management of alopecia areata.
| S-EPMC10687936 | biostudies-literature
Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata. 5 biological replicates of skin samples from 5 separate AA patients compared with 5 similar scalp samples from healthy control patients
2014-08-17 | E-GEOD-45512 | biostudies-arrayexpress