INTRODUCTION
Alopecia areata (AA) is a chronic autoimmune disorder resulting in patchy, non-scarring hair loss on the face, body, and/or scalp.1 It is postulated to result from the collapse of hair follicle immune privilege, which, under normal conditions, is maintained by suppressing MHC class I expression and producing immunosuppressive factors.2 In AA, loss of this immune privilege leads to upregulation of MHC class I and II molecules, infiltration of immune cells, and the release of Th1-mediated pro-inflammatory cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-12, IL-15, and IL-18. This process disrupts the normal hair cycle by inducing premature catagen or telogen and ultimately resulting in hair loss.2 The driving role of Th2-mediated cytokines in AA has also been suggested, as studies have reported elevated serum levels of IL-4, IL-13, and CC chemokine ligand (CCL)17 in patients with AA.3 AA has also been associated with other autoimmune diseases, such as asthma, atopic dermatitis (AD), psoriasis, systemic lupus erythematosus, thyroiditis, vitiligo, and allergic rhinitis.4-6
Common AA treatments include topical, intralesional, or oral corticosteroids, minoxidil, cyclosporine, methotrexate, diphenylcyclopropenone, light-based therapies, and small-molecule drugs such as Janus kinase (JAK) inhibitors.2,4 Recent case reports and case series have proposed off-label biologic therapies, such as dupilumab and secukinumab, as novel treatments for AA.1,5,7-10 Conversely, multiple studies have reported the development of AA in patients treated with dupilumab and secukinumab.6,8,11-15 Given this mixed evidence, this review evaluates the current literature on dupilumab and secukinumab as treatments and triggers of AA.
Biologics as Treatment
Emerging literature has reported dupilumab, an IL-4 and IL-13 receptor antagonist, as an AA treatment.7 Currently approved in pediatric and adult patients for moderate to severe atopic dermatitis (AD), dupilumab has a well-established safety profile, with conventional adult dosing of 300 mg injected subcutaneously biweekly.16 Dupilumab has gained increasing attention as an offlabel AA treatment, particularly in patients with comorbid AD, given the potential overlapping Th2-mediated mechanisms.5 Dupilumab may be especially useful in AA patients with elevated serum IgE, a potentially predictive biomarker for treatment response.5 Evidence has also demonstrated reductions in Th2-related markers and increases in hair keratins in AA patients treated with dupilumab.5
A retrospective study of nine patients with AA and concurrent AD demonstrated significant improvement in AA on dupilumab therapy at conventional dosing, with 89% achieving a 50% improvement in their Severity of Alopecia Tool (SALT) score after 24 months.5 Further studies have demonstrated the utility of dupilumab, with one report of complete hair regrowth after 17 months of treatment in an alopecia totalis patient refractory to typical therapies, and a case series demonstrating that seven out of ten AA patients achieved ≥50% hair regrowth after a median of eight months of treatment with conventionally dosed dupilumab.1,7 Additionally, a recent systematic review reported that 77.5% of AA patients (n=89) experienced hair regrowth with dupilumab.8 Overall, there is substantial evidence of successful, well-tolerated AA treatment with dupilumab, particularly in patients with comorbid AD, and additional evidence of efficacy even in patients without AD. However, the studies are largely limited to case reports, reviews with small sample sizes, and retrospective designs. Further research is needed to clarify the mechanistic details of dupilumab in AA treatment and to assess its utility in AA without concurrent AD.
Secukinumab, an IL-17 antagonist, is another biologic therapy proposed as an off-label treatment for AA. Approved for psoriasis, psoriatic arthritis, and hidradenitis suppurativa, secukinumab has also been used for AA, with one report demonstrating significant hair regrowth in a patient with a 25-year history of alopecia universalis and a 2-year history of psoriasis, three months after initiating secukinumab 300 mg monthly.9,17 The patient subsequently experienced alopecia recurrence after discontinuing therapy six months later.9
IL-17 inhibition in AA management remains poorly understood. While AA is predominantly driven by Th1-mediated processes, elevated serum and lesional scalp levels of IL-17 have been reported, prompting the hypothesis for IL-17 inhibition in alopecia management.10 However, evidence remains inconsistent and has not been clearly linked to disease severity or duration.10 Nonetheless, the presence of elevated serum IL-17 in a subset of patients, coupled with reports of successful treatment, supports continued exploration of secukinumab in individuals with AA.
While further studies are warranted, both dupilumab and secukinumab have emerged as potential treatment options for AA in patients with comorbid conditions for which these biologics are indicated. This supports the possibility that reducing systemic inflammation from the underlying disease may also benefit AA, especially in individuals refractory to conventional treatment.
Biologics as Trigger
Although several studies have suggested dupilumab and secukinumab as potential treatments for AA, there is also growing evidence demonstrating opposing findings. A recent retrospective
