Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase‐4 inhibitors

Abstract

Management options for moderate‐to‐severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long‐term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side‐effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase‐4 (PDE‐4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE‐4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long‐term studies could shed light on the utility of the newer agents in altering the progression of AA.

Alopecia areata: What's new in the diagnosis and treatment with JAK inhibitors?

“…JAK inhibitors provide a clear example of the treatment development process for patients with AA. [61][62][63] Evidence from animal models and humans suggests two major potential targets in AA: the IFNγ pathway (dependent on JAK1/2) and the IL-15 pathway (dependent on JAK1/3). 61,64 Consequently, all the peroral JAK inhibitors effective for AA are selective to either JAK1, or JAK3.…”

“…61,64 Consequently, all the peroral JAK inhibitors effective for AA are selective to either JAK1, or JAK3. 61,63 The feedback loop of IFNγ and IL-15 between CD8 + T cells and HF epithelial cells is thought to be the driving force of the disease state. open-label studies of various JAK inhibitors: i.e., some patients experience a dramatic hair regrowth.…”

Comparative efficacy of oral Janus kinase inhibitors and biologics in adult alopecia areata: A systematic review and Bayesian network meta‐analysis

“…2 Recent advancements in understanding the pathogenesis of AA have identified new agents with the potential to reverse alopecia and maintain hair regrowth, such as the cytokine-targeting biologics, and small molecules that inhibit the Janus kinase (JAK) family of tyrosine kinases or phosphodiesterase-4 (PDE-4). 3 The JAK family comprises four intracellular enzymes: JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). These enzymes interact with type 1 and 2 cytokine receptors and mediate the intracellular signal transduction that affects on cells' migration, proliferation, differentiation and apoptosis.…”

Interleukin‐13 as a promising therapeutic target for alopecia areata associated with atopic dermatitis

“…Current alternative therapeutic options in the management of AA represent JAK inhibitors (ruxolitinib and tofacitinib), a phosphodiesterase-4 inhibitor (apremilast), and biologics (aldesleukin, dupilumab and secukinumab). 5 Tralokinumab and dupilumab probably have particular potency to induce hair regrowth and to improve QoL impairment for atopic AA with high total serum IgE levels.…”

“…Currently, baricitinib, Janus kinase (JAK) 1/2 inhibitor, and ritlecitinib, JAK3/ tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, are appliable for moderate‐to‐severe refractory AA. Current alternative therapeutic options in the management of AA represent JAK inhibitors (ruxolitinib and tofacitinib), a phosphodiesterase‐4 inhibitor (apremilast), and biologics (aldesleukin, dupilumab and secukinumab) 5 . Tralokinumab and dupilumab probably have particular potency to induce hair regrowth and to improve QoL impairment for atopic AA with high total serum IgE levels.…”