Nuevo tratamiento para alopecia a reata...

How Should Physicians Respond to the Latest Research on Treating Alopecia?

Tofacitinib for the Treatment of Severe Alopecia Areata and Variants: A Study of 90 Patients 

Liu LY, Craiglow BG, Dai F, King BA
J Am Acad Dermatol. 2017;76:22-28

Alopecia, in all its various forms, has been extremely frustrating to patients and physicians alike, who have had too few options for treatment. It is a condition that often causes significant stress because of its cosmetic manifestation, so finding an effective treatment has been a long time coming.

This recent study is promising, but should physicians start prescribing full steam ahead? What are the alternatives, and what's on the horizon for future treatments?

Let's take a look.

Background

Alopecia areata (AA) and its more severe variants—alopecia totalis (AT) and alopecia universalis (AU)—are autoimmune disorders characterized by variable degrees of hair loss, discrete or diffuse patches of nonscarring hair loss, and perifollicular lymphocytic infiltrates with tapered and broken hair shafts on histopathology. The disease presents in both children and adults, with a worse prognosis seen with early-onset, extensive alopecia (AT or AU) or an ophiasis (band-like, temporal and occipital) pattern. AA is not a rare disease, with a lifetime incidence of up to 1.7% in the general population and higher rates in individuals with autoimmune or inflammatory diseases, including Hashimoto thyroiditis, vitiligo, atopic dermatitis, and psoriasis.

Mild AA typically resolves spontaneously, with intralesional corticosteroid injections and topical minoxidil commonly used to expedite hair regrowth. In contrast, more extensive AA is notoriously challenging to treat: Although some studies have suggested that high-dose, intermittent pulsed corticosteroids may yield temporary hair regrowth, relapse rates are discouragingly high.

Janus kinase (JAK) inhibitors, such as ruxolitinib and tofacitinib, suppress cytotoxic T lymphocytes and are indicated for the treatment of rheumatoid arthritis, psoriasis vulgaris, and psoriatic arthritis. JAK inhibition reversed CD8(+)NKG2D(+) T-lymphocyte–mediated AA in a murine model, and the oral JAK 1/3 inhibitor tofacitinib dramatically reversed AA in an index patient being treated for plaque psoriasis. These intriguing observations prompted a 3-month open-label trial of 66 patients with AA, showing promising short-term results.

Study Summary

Inspired by these encouraging data, Liu and colleagues conducted an open-label, retrospective study of 90 adults (median age, 34.5 years; 55.6% female) with AA (14.4%), AU (83.3%), or AT (2.2%). Of this initial group, 65 trial-eligible patients received monotherapy with tofacitinib 5 mg twice daily for the first 2-3 months of treatment. After this induction phase, 29% of patients received a higher tofacitinib dose (up to 10 mg orally twice daily), and 28% of patients started adjuvant therapy with pulsed prednisone.

The primary endpoint was the percentage change in the Severity of Alopecia Tool (SALT) score between the first and last visits. Treatment safety was assessed with laboratory studies, examination, and review of systems.

Results

1. After 4-18 months of tofacitinib therapy, 77% of patients achieved a clinical response.

2. 58% of patients achieved at least a 50% improvement in SALT scores, and 20% showed a complete response (full hair regrowth) after a median of 15 months of treatment.

3. Patients with AA (n = 13) were better responders than those with AT or AU (n = 52) (81.9% improvement in SALT scores vs 59.0% improvement, respectively).

4. No serious adverse events or laboratory abnormalities were observed after a mean of 1 year of treatment. The most common adverse events were upper respiratory infections (28.9%), headache (14.4%), and acne (7.8%).

Discussion

In this small but statistically significant study, the oral JAK 1/3 inhibitor tofacitinib showed impressive efficacy in the treatment of AA, AT, and AU. Of note, this trial excluded patients with AA, AU, or AT of greater than 10 years' duration, because prior studies had showed poor tofacitinib efficacy in this group with chronic disease.

As Liu and colleagues point out, their trial lacked a control group, and roughly 28% of patients went on to receive adjuvant therapy with pulsed corticosteroids during the trial period. They noted a low spontaneous relapse rate of 7.7%; however, the duration of treatment ranged from 4 to 18 months (median, 12 months). Hence, we do not know whether tofacitinib therapy can induce long-term disease remission, or whether the disease process will resume after drug cessation.

This study showed tofacitinib efficacy in adult patients, but oral JAK 1/3 inhibitors also shows promise in adolescents with AA, AU, and AT. A small study (13 patients) showed a median change in SALT score of 93% after a mean of 6.5 months of tofacitinib therapy, and topical JAK inhibitors can induce significant hair regrowth in localized AA.

Viewpoint

Although tofacitinib therapy was not associated with significant adverse events in this study group, oral JAK inhibitors used to treat rheumatoid arthritis have been associated with significant adverse events, including rare cancers (soft tissue and lymphoma) and serious infections. Whether these risks are unique to patients with rheumatoid arthritis because of comorbidities and concurrent medications, remains to be determined. This is something that many clinicians may not want to gloss over. Some might find it prudent to discuss risks and benefits with patients so that they can make a truly informed decision.

JAK 1/3 inhibitors, such as tofacitinib, are a promising new treatment for AA, AU, and AT. Although response rates were not as dramatic for AU and AT, the efficacy in these more severe forms of autoimmune alopecia is especially impressive, given the lack of therapeutic alternatives. Future studies should adopt a randomized, prospective, placebo-controlled design and include long-term follow-up, both with and without maintenance tofacitinib therapy.

According to the National Alopecia Areata Foundation, clinical studies of topical treatments, psychological interventions, and additional JAK inhibitor strategies are under way. Until then, we watch and wait.

Emoliente con glicerol y parfina utilen dermatitis atopica.

Published in Dermatology

Journal Scan / Research · March 21, 2017

Regular Use of an Emollient Containing Glycerol and Paraffin Reduces Flares in Children With Atopic Dermatitis

TAKE-HOME MESSAGE

• Children from ages 2 to 6 with mild to moderate atopic dermatitis (AD; N = 335) were randomized to receive emollients (15% glycerol, 10% soft paraffin) twice daily vs no emollient. The children treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, and lower IGA and SCORAD scores than those who were not. At 12 weeks, significantly fewer children treated with emollients required corticosteroids or immunosuppressants (23.6%) than patients not treated with emollients (43.3%). 

• Although emollients are part of standard treatment for AD, there has been limited evidence that they prevent flares. This study suggests that regular emollient use in children with mild to moderate AD can reduce flares and use of corticosteroids.

  – InYoung Kim, MD, PhD

Pediatric Dermatology

Prevention of Flares in Children With Atopic Dermatitis With Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study

Pediatr Dermatol 2017 Mar 07;[EPub Ahead of Print], GS Tiplica, A Kaszuba, L Malinauskienė, P Konno, F Boralevi, E Garrigue, M Saint-Aroman, A Delarue 

Benjamin Hidalgo-Matlock

Skin Care Physicians of Costa Rica

4000-1054

2208-8206

Please excuse the shortness of this message, as it has been sent from a mobile device.

Otro sistema para preservar el cabello en pacientes con quimio para cancer de mama.

FDA Gives Marketing Clearance For Scalp Cooling System For Reducing Hair Loss In Breast Cancer Patients Undergoing Chemotherapy.

Medscape (4/19, Mulcahy) reports that the FDA "has given marketing clearance for the Paxman Scalp Cooling System for reducing hair loss in breast cancer patients undergoing chemotherapy." This "device becomes the second hair loss prevention system okayed by the FDA following the 2015 clearance of the DigniCap Cooling System."

        Healio (4/19) reports that the new "device is intended to reduce the amount of chemotherapy that reaches the hair follicles, reduce drug diffusion through the cell membrane, decrease cell division, reduce active transport mechanisms and generally reduce metabolic activity."

Benjamin Hidalgo-Matlock

Skin Care Physicians of Costa Rica

4000-1054

2208-8206

Please excuse the shortness of this message, as it has been sent from a mobile device.

Cambios genéticos y moleculares en Alopecia Androgenética Masculina...

Original Article

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways

Authors

• Accepted manuscript online: 12 April 2017Full publication history
• DOI: 10.1111/bjd.15577  View/save citation
• Cited by (CrossRef): 0 articlesCheck for updates 
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• This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.15577

Abstract

Background

Male androgenetic alopecia (AGA) is the most common form of hair loss in men and is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined.

Objectives

Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless/bald men with premature AGA and healthy volunteers.

Results

This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, lower expression of CYP27B1 in AGA subjects supports the notion that changes in vitamin D metabolism contributes to hair loss.

Conclusion

This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave way for new therapeutic approaches.

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