• Alopecia areata: drug therapy

Which method achieves the best hair growth rates?

Alopecia areata (AA) manifests as acute or chronic non-scarring hair loss. Diphenylcyclopropenone and Janus kinase inhibitors have a significantly higher remission rate compared with the spontaneous course, especially in severe AA. For less severe infestations, steroids in various forms of application are considered first-line treatment, and minoxidil solution is occasionally used. In addition, there are many other therapeutic options in the off-label area.

According to current knowledge, alopecia areata (AA) is a chronic autoimmune disease that leads to circumscribed or disseminated hair loss by breaking the immune privilege of the hair follicle [1]. The flare-up of AA is associated with a significantly shortened anagen phase of the hair growth cycle (Fig. 1) [3,11]. The inflammatory infiltrate and disruption of hair follicle (HF) activity in AA occurs mainly around and in the bulb area, whereas the HF stem cell niche in the bulge area of the permanent part of the hair follicle is spared [2,3]. Often, in the case of spontaneous or drug-induced remission, the hair grows back unpigmented [4]. At this year’s Swiss Derma Day, Stephanie Marie Huber, MD, Dermatology, University Hospital Basel, provided an update on treatment options for AA [5].

Severity and age as important selection criteria for therapy

The Severity of Alopecia Tool (SALT score) was developed to evaluate the extent and progression of AA [6]. The SALT score can be used not only for research purposes but also in clinical practice as a good measure for assessing the extent of AA in the scalp [7]. Based on the estimated SALT score, different degrees of hair loss severity can be distinguished, ranging from 0 (no hair loss) to 100 (100% hair loss) [3].

Currently used treatment methods for AA depend on age and initial extent of alopecia (Table 1) [3,5]. Topical corticosteroids are first-line therapy for children <10 years (regardless of severity). Intralesional injection of corticosteroids is a first-line recommendation in >10-year-old individuals with SALT<30, with monotherapy or combination with topical corticosteroids. Long-term use of systemic corticosteroids is not recommended because of the risk of side effects. In >10-year-old individuals with extensive AA (SALT>30), in addition to minoxidil solution and systemic corticosteroids, topical sensitization with DPCP or the use of Janus kinase inhibitors (JAK-i) is further recommended. Topical corticosteroids may be used as adjunctive therapy in severe AA. Treatment with each of the aforementioned therapeutic options should be administered consistently for at least 12 weeks to assess response [5]. JAK-i have been shown in clinical trials for distinct forms of AA to be an effective therapeutic option with rapid onset of action. AA promotes JAK-mediated IFN-γ and IL-15 production and an inflammatory feedback loop that maintains the local inflammatory response. JAK-i interfere with the JAK-STAT pathway and block downstream signaling of various pro-inflammatory cytokines.

DPCP – for over 10 year olds with severe infestation.

In patients over the age of 10 with hair loss greater than 30%, topical immunotherapy with diphenylcyclopropenone (DPCP) has been considered the gold standard to date. “DPCP represents the only treatment modality other than JAK-i that has a higher remission rate compared with the spontaneous course,” said Dr. Huber [5]. The remission rate depends on the initial extent of alopecia. DPCP is contraindicated in pregnant and lactating women, and special caution should be exercised in patients with darker skin types, as there is a risk of depigmentation. Initial sensitization at 2% is followed by a weekly increase in dose until the desired therapeutic contact dermatitis is achieved. “If there is no hair growth after about 6-12 months of therapy, the therapy should be discontinued,” said the speaker [5]. Adverse side effects include pigmentary shifts, eczema scattering, reactive nuchal lymphadenopathy, and local vesiculobullous reactions.

Baricitinib – adults with SALT score ≥50 may benefit

Especially in severe alopecia areata, JAK inhibitors represent an interesting new therapeutic option, Dr. Huber reported [5]. JAK-i have been successfully used for a long time in chronic inflammatory diseases. Baricitinib is the first JAK inhibitor approved in the EU for the treatment of severe AA (SALT score ≥50) since 06/2022.

In the two identically designed phase III trials BRAVE-AA1 and BRAVE-AA2, 654 and 546 patients with hair loss of ≥50% (SALT score ≥50), respectively, were randomized in a 3:2:2 ratio to the baricitinib 4 mg/d vs. barictinib 2 mg/d vs. placebo study arms [8]. The primary endpoint was hair loss ≤20% (SALT score ≤20). The results were published in the New England Journal of Medicine . In BRAVE-AA1, after 36 weeks, approximately 39% on baricitinib 4 mg, approximately 23% of patients on baricitinib 2 mg, and approximately 6% of patients on placebo demonstrated a SALT score of 20.

In BRAVE-AA2, the corresponding figures were 36% and 19%, respectively, in the two treatment arms and 3% under placebo. Thus, orally administered baricitinib was clearly superior to placebo in terms of hair regrowth after 36 weeks. The most common side effects were acne, increase in creatinine kinase, and increase in HDL/LDL cholesterol levels. To assess the longer-term efficacy and safety of baricitinib in alopecia areata, longer-designed studies are desirable because alopecia per se has a very variable course between regrowth and reappearance of hair, the speaker explained.

Ritlecitinib and brepocitinib – informative trial data.

A phase II extension study published in 2022 examined the longer-term effects of two other JAK-i for the treatment of AA [9]: Ritlecitinib (JAK3/TEC inhibitor) and Brepocitinib (Tyk2/JAK1 inhibitor). The study was double-blinded in the first phase (24 weeks), after which subjects were assigned to the following study arms in a single-blinded fashion depending on treatment response:

  • Placebo non-response: Switch to active treatment with ritlecitinib/brepocitinib.
  • Active non-responders (no improvement of ≥30% by week 24 despite active treatment): Continuation of active treatment with ritlecitinib/brepocitinib.
  • Active responders (under active treatment an improvement of ≥30% after 24 weeks): Switch to placebo until reaching the retreatment criterion (loss of ≥30% of hair regrown in the double-blind phase).

It was found that about 64% of active responders to ritlecinib and about 61% to brepocitinib, respectively, required retreatment with the JAK-i after an average of 16.1 weeks (n=22) and 24.1 weeks (n=24). Thus, the data suggest that longer-term treatment with the JAK-i is needed, Dr. Huber explained.

The possible side effects of JAK-i are well known from rheumatology and can be found in the drug information of the respective preparation. In acute infections, JAK-i should be paused, which is readily achievable due to oral administration and the short half-life of the drugs [12]. In addition to ruling out chronic infectious diseases before starting therapy (e.g., hepatitis, TB), special attention should be paid to herpes virus-associated infections. The use of live vaccines immediately before or during treatment with JAK-i is not recommended. Vaccinations with inactivated vaccines are possible during treatment with JAK-i. To prevent varicella-zoster reactivation, vaccination with Shingrix® varicella-tot vaccine is recommended.

Congress: Swiss Derma Day

Literature:

  1. Busch D, Sticherling M: Die Alopecia areata – klinisches Bild und Therapieansprechen einer heterogenen Erkrankung. P091, https://onlinelibrary.wiley.com/doi/full/10.1111/ddg.13796, (letzter Abruf 13.01.2023)
  2. Lee YB, Jun M, Lee WS: Alopecia areata and poliosis: A retrospective analysis of 258 cases. JAAD 2019; 80: 1776-1778.
  3. Lintzeri DA, et al.: Alopecia areata – Aktuelles Verständnis und Management. JDDG 2022; 20(1): 59–93.
  4. Bruhn I, Frenzel U-R, Landeck L: Pigmented hair growth after combined systemic corticosteroid therapy with intralesional triamcinolone injection for alopecia areata. P090, https://onlinelibrary.wiley.com/doi/full/10.1111/ddg.13796,(last accessed Jan. 13, 2023)
  5. «Alopecia areata – neue Evidenz», Dr. med. Stephanie Marie Huber, Swiss Derma Day and STI reviews and updates, 12.01.2023
  6. Olsen EA, et al: Alopecia areata investigational assessment guidelines – Part II. National Alopecia Areata Foundation. JAAD 2004; 51: 440-447.
  7. Meah N, et al.: The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata. JAAD 2021; 84: 1594–1601.
  8. King B, et al.: BRAVE-AA Investigators. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med 2022; 386(18): 1687–1699.
  9. Peeva E, et al.: Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial. JAAD 2022; 87(2): 390–393.
  10. Messenger AG, et al: British Association of Dermatologists’ guidelines for the management of alopecia areata 2012. Br J Dermatol 2012; 166(5): 916-926.
  11. Carrasco E, Soto-Heredero G, Mittelbrunn M: The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics. Int J Mol Sci 2019; 20(11): 2758.
  12. Klein B, Treudler R, Simon JC: JAK-Inhibitoren in der Dermatologie – kleine Moleküle, grosse Wirkung? Übersicht über Wirkmechanismus, Studienergebnisse und mögliche unerwünschte Wirkungen. JDDG 2022; 20(1): 19-25.
  13. Swissmedic: Medicinal Product Information, www.swissmedicinfo.ch,(last accessed 16.01.2023).

DERMATOLOGIE PRAXIS 2023; 33(1): 30–31

Autoren
  • Mirjam Peter, M.Sc.
Publikation
  • DERMATOLOGIE PRAXIS
Related Topics
You May Also Like