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Alopecia areata

New drugs for alopecia areata

Presented by: Prof. Spyridon Gkalpakiotis Department of Dermatovenereology, Third Faculty of Medicine and University Hospital of Kralovske Vinohrady, Prague, Czech Republic.
  • Based on better understanding of the pathophysiology of alopecia areata, a large number of targeted therapies are currently being investigated for alopecia areata.
  • Among these, JAK inhibitors appear to be highly promising agents for treatment of alopecia areata.

Alopecia areata affects both children and adults and hair of all colours. [1] Up to 66% of patients are younger than 30 years of age, and only 20% are older than 40 years, with no sex predilection. Alopecia areata is further associated with an increased overall risk of other autoimmune disorders: lupus erythematosus in 0.6% of patients, vitiligo in 4% and autoimmune thyroid disease in up to 28% of cases.

  • There are two primary option for management: [1]
    • use of an immunosuppressive regimen (preferable for patients with acute and rapidly progressing alopecia areata), or
    • an immune-deviation strategy that manipulates the intracutaneous inflammatory milieu (preferred for patients with the chronic, relapsing form).
  • At present, only two approaches reach the level of evidence-based medicine: intralesional injections of glucocorticoids and the induction of contact allergy.
  • The possibility to use JAK inhibitors for alopecia areata arose from an unusual case report in which a patient with plaque psoriasis being treated with tofacitinib experienced a reversal in alopecia universalis. [2]
  • We now know that Janus kinase-signal transducer and activator of transcription (JAK-STAT) is a signalling pathway that is crucial in maintaining the CD8+ NKG2D+ T cell inflammatory infiltrate which is typical of alopecia areata. [3]
  • At present, at least 3 JAK inhibitors are under investigation in alopecia areata: tofacitinib, baricitinib and ruxolitinib. [4]
  • In a study with tofacitinib in 66 patients (>50% scalp hair loss, alopecia totalis and universalis) treated with tofacitinib 5 mg twice daily, 32% of patients were intermediate responders (improvement in S ALT score ≥5% and ≤50%) and 32% were strong responders (changes in SALT score ≥50%).[4]
  • Patients with chronic alopecia areata were less likely to be good responders; drug cessation resulted in disease relapse in a mean of 8.5 weeks. [4]
  • A small study in 12 patients with moderate-to-severe alopecia areata on oral ruxolitinib, 20 mg twice per day, for 3–6 months, followed by 3 months follow-up off drug reported that after 6 months 75% of patients (9 of 12) had a strong response to treatment (defined as >50% hair regrowth). [4]
  • At the end of the treatment, shedding started 3 weeks after cessation of ruxolitinib. [4]
  • Most recently, the efficacy, side effects and durability of ruxolitinib was compared to tofacitinib in the treatment of severe alopecia areata. [5]
  • 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.
  • Baricitinib is an oral selective inhibitor of JAK1 and JAK2, approved for the treatment of rheumatoid arthritis.
  • To date only isolated case reports have been published on baricitinib in alopecia areata, although a placebo-controlled trial involving 725 subjects comparing baricitinib to placebo in moderate to severe alopecia areata is currently recruiting (NCT03570749).
  • Apremilast is a disease modifying antirheumatic drugs (DMARD) used in psoriasis; a small retrospective analysis on 15 patients showed that apremilast could be a potential treatment for refractory alopecia areata at doses lower than that approved for psoriasis; however, further study is needed. [6]
  • Fumaric acids inhibit T-suppressor cells and T-helper cells by the inhibition of the cytokines INF-γ, IL-2, IL-12 and TNF-α, and block ICAM and the proliferation of keratinocytes.
  • A retrospective analysis of 13 patients with various types of alopecia showed that those with alopecia totalis showed no response, while 67% those with alopecia universalis partially responded; 50% of alopecia areata patients had full regrowth of hair after a mean period of treatment of 5.2 months. [7]
  • However, relapse was seen after a mean of 3.3 months following cessation of therapy.
  • A number of other agents are in the early stages of investigation.
  • These include BNZ-1 (a selective and simultaneous inhibitor of cytokines IL-2, IL-9 and IL-15), tralokinumab (an IgG4 humanised monoclonal antibody that specifically binds IL-13) and dupilumab (a Th2 antagonist that blocks IL-4 receptor α, inhibiting IL-4 and IL-13). [4]
  • A large number of targeted therapies are currently under investigation for alopecia areata.

Key messages/Clinical perspectives

  • JAK inhibitors show particular promise for treatment of alopecia areata.


References

References


  1. Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med. 2012 Apr 19;366(16):1515-25.
  2. Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol. 2014 Dec;134(12):2988-90.
  3. Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019 May;33(5):850-6.
  4. Ocampo-Garza J, Griggs J, Tosti A. New drugs under investigation for the treatment of alopecias. Expert Opin Investig Drugs. 2019 Mar;28(3):275-284.
  5. Almutairi N, Nour TM, Hussain NH. Janus kinase inhibitors for the treatment of severe alopecia areata: An open-label comparative study. Dermatology. 2019;235(2):130-6.
  6. Taneja N, Gupta S. Apremilast is efficacious in refractory alopecia areata. J Dermatolog Treat. 2019 May 6:1-3.
  7. Niculescu L, Heppt MV, Varga R, et al. Retrospective analysis of the application of fumaric acid esters in 13 patients with alopecia areata. Eur J Dermatol. 2018 Jun 1;28(3):376-7.

Presenter disclosure information: S Gkalpakiotis: None disclosed.

Medical writer: Patrick Moore, PhD

Reviewer: Martina Lambertini, MD

Local reviewers: Martina Lambertini, MD (Italian); Alain Brassard, MD (French); Jorge Moreno González, MD (Spanish); Swen Malte John, MD, PhD (German); Marcelo Arnone, MD (Portuguese)

Scientific Editor: Prof. Brigitte Dréno, MD


CLINICAL TRIALS

PSORIASIS

Efficacy and safety of ixekizumab in a phase 3, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis

Presented by: Prof. Kim A. Papp, Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Canada

ATOPIC DERMATITIS

Efficacy and safety of baricitinib in combination with topical corticosteroids in moderate to severe atopic dermatitis: results of a phase 3 randomized, double-blind, placebo-controlled 16-week trial (BREEZE-AD7)

Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany

PRURIGO NODULARIS

Phase 2b study of nemolizumab in patients with moderate to severe prurigo nodularis and associated severe pruritus

Presented by: Prof. Sonja Ständer, Department of Dermatology and Center for Chronic Pruritus (KCP), University Hospital Münster, Germany

VITILIGO

Efficacy and safety of a 52-week, randomized, double-blind trial of ruxolitinib cream for the treatment of vitiligo

Presented by: Dr. Amit G. Pandya, University of Texas Southwestern Medical Center, Dallas, TX, USA
 

EMERGING TERAPIES

PSORIASIS

Emerging therapies for psoriasis

Presented by: Prof. Michel Gilliet, Department of Dermatology, Lausanne CHUV, Switzerland

ATOPIC DERMATITIS

New and emerging therapies in atopic dermatitis

Presented by: Prof. Dagmar Simon, Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland

ONYCHOMYCOSIS

Emerging treatments for onychomycosis

Presented by: Dr. Ditte Marie L. Saunte, Department of Dermatology, Institute for Clinical Medicine, Zealand University Hospital, Roskilde, Denmark
 

REVIEW & UPDATES

ACNE & ROSACEA

Isotretinoin for acne and rosacea

Presented by: Dr. Pedro Mendes-Bastos, Dermatology Centre, Hospital CUF Descobertas, Lisbon, Portugal

ALOPECIA AREATA

New drugs for alopecia areata

Presented by: Prof. Spyridon Gkalpakiotis, Department of Dermatovenereology, Third Faculty of Medicine and University Hospital of Kralovske Vinohrady, Prague, Czech Republic.

DERMATOSURGERY

Update in dermatosurgery

Presented by: Prof. Eduardo Nagore, Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain

EPIDERMOLYSIS BULLOSA

New start of gene therapy in epidermolysis bullosa

Presented by: Prof. Leena K. Bruckner-Tuderman, University Medical Center, Albert-Ludwigs-University of Freiburg, Germany

MELANOMA

Treatment resistance in metastatic melanoma

Presented by: Prof. Martin Röcken, Department of Dermatology, Eberhard-Karls-University Tübingen, Germany

SCAR TREATMENT

Future of medical scar treatment

Presented by: Prof. Gabriella Fabbrocini, Department of Dermatology, University of Naples Federico II, Naples, Italy
 

EDUCATION FORUM

NON-MELANOMA SKIN CANCER

Systemic treatments of non-melanoma skin cancer

Presented by: Prof. Henrik F. Lorentzen, Department of Dermatology, Aarhus University Hospital, Denmark
 

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