Apremilast in Refractory Alopecia Areata

Abstract

Alopecia areata (AA) is a common disease characterized by nonscarring hair loss. There are no satisfactory therapies for extensive cases. Systemic immune suppressants are usually used despite their nonspecific actions and often associated side effects. Apremilast is an oral, small-molecule, inhibitor of phosphodiesterase 4 approved for the treatment of psoriasis and psoriatic arthritis. Its use in AA has shown variable results. Whereas a recent reduced clinical trial concluded a lack of efficacity, several case reports demonstrate a significant improvement. We report four cases of extensive AA successfully treated with apremilast.

INTRODUCTION

Alopecia areata (AA) is a common and complex T-cell-mediated disease, characterized by nonscarring hair loss. Its lifetime risk is 2%, with a peak incidence in young adults.[1] AA, the most common clinical presentation, is one or more bald circumscribed patches on the scalp. In up to 25% of cases, hair loss can progress to a total loss of scalp hair (alopecia totalis [AT]) or a complete body hair loss (alopecia universalis [AU]).[1] In patients with extensive hair loss, spontaneous hair growth is rare. There is a lack of effective treatments for extensive AA, AT, and AU, with no universally proven therapy that induces remission.[2] Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate. In March 2014, the US Food and Drug Administration (FDA) approved apremilast for the treatment of adult patients with active psoriatic arthritis. Subsequently, it received FDA approval in September 2014 for the treatment of moderate-to-severe plaque psoriasis in patients for whom phototherapy or systemic therapy is appropriate.[3] Apremilast is currently being tested in trials for atopic dermatitis (NCT02087943) and other inflammatory dermatological conditions (such as Behçet disease NCT00866359). We report four cases of severe AA successfully treated with apremilast at a dose of 30 mg twice daily after 5-day-initial titration (dosing recommendations for psoriasis).

CASE REPORTS

Case 1

A 44-year-old female patient, with a 2 year history of AU, was referred to our dermatological department. She had no other medical history apart from AU previously treated with topical 5% minoxidil twice a day, oral finasteride (2.5 mg/day), oral corticosteroids, and methotrexate (15 mg/week) with no significant response. Physical examination revealed an AU with a complete loss of body hair [Figure 1a]. Laboratory findings showed no abnormalities. Three months after having finished methotrexate, we started apremilast off-label with the patient's agreement. After 5 weeks of treatment, very discrete hair regrowth was observed [Figure 1b]; however, a significant response was seen after 12 weeks of treatment with some discrete patches of hair loss (severity of alopecia tool [SALT] 40) [Figure 1c].

Figure 1.

Patient 1 (a) alopecia universalis showing a complete loss of scalp hair, (b) very discrete hair regrowth after 5 weeks of treatment with apremilast, and (c) significant hair regrowth after 12 weeks of treatment showing discrete patches of hair loss (severity of alopecia tool 40)

Case 2

A 28-year-old female presented to our consultation with a 6-month history of severe AA [Figure 2a and b]. She had no other medical history, and no abnormalities were found in laboratory test results. We tried oral corticosteroids with no response and important side effects. Methotrexate at a dose of 15 mg/week was also introduced without effect. Physical examination revealed severe AA multilocularis (SALT 67). Treatment with oral apremilast was started as label dosing after a 2-month washout period. After 8 weeks of treatment, the patient showed a significant improvement (SALT 16,2) [Figure 2c and d] with no side effects apart from mild diarrhea.

Figure 2.

Patient 2 (a and b) alopecia areata multilocularis (severity of alopecia tool 67) showing an extensive loss of scalp hair and eyebrows, (c and d) significant hair regrowth after 8 weeks with apremilast (severity of alopecia tool 16,2)

Case 3

A 25-year-old male with a 7-year history of atopic dermatitis was referred to our dermatological service because he had developed a big size bald circumscribed patch on the scalp for the past 10 months. Atopic dermatitis was treated with topical steroids, narrow-band ultraviolet B, and oral corticosteroids, without lasting response. Dermatological examination revealed atopic dermatitis (eczema area and severity index [EASI] 7) and bald patches with yellow dots in the dermoscopy in the parieto-occipital area that made us consider the diagnosis of AA monolocularis (SALT 7,6). Treatment with oral apremilast off-label was started. After 8 weeks of treatment, complete hair regrowth was observed with a significant improvement in atopic dermatitis (EASI 3,5).

Case 4

A 41-year-old male with a 2-year history of psoriasis, treated in the past 2 years with methotrexate, was referred to our department with AA mutilocularis. Dermatological examination revealed several typical psoriasis plaques (psoriasis area severity index [PASI] 12) with extensive patches of hair loss affecting the eyebrows, the temporal and the parietal regions of the scalp (SALT 13,6). He was prescribed topical 5% minoxidil twice a day, topical diphencyprone, intralesional corticosteroids, and oral methotrexate at a dose of 15 mg/week with no lasting effect. We started oral apremilast, and after 6 weeks, the patient showed a significant improvement in psoriasis (PASI 4) lesions with an important hair regrowth on the scalp (SALT 7,6).

DISCUSSION

The limited treatment options for AA are derived from the incomplete understanding of its immune pathophysiology, spurring investigation into the cytokine pathways of the disease. PDE4 is increased in human AA lesions;[4] thus, it can be speculated that apremilast may be a treatment option for AA as it was shown in a humanized AA mouse model using scalp grafts.[5] Current clinical trials for the use of Janus kinase inhibitors, abatacept, aldesleukin, secukinumab, and tralokinumab in AA, are taking place.[6] The major advantages of apremilast are the high-safety profile and the minimal monitoring requirements, despite its broad action.

The association between AA and psoriasis, as well as AA and atopic dermatitis, is not frequent. Patients with both conditions can get benefit from apremilast treatment, as presented in our last two cases. Some recent studies and clinical trials showed a lack of efficacy of apremilast in severe cases of AA,[7,8] whereas other case reports demonstrated considerable good responses.[9,10] Mikhaylov et al.[7] evaluated clinical response (percent change in SALT score) at weeks 24 and 48; however, we show an earlier response without enough surveillance time. Their baseline mean SALT score (88) is also higher than in our case series (two patients associated moderate psoriasis and atopic dermatitis also getting benefit from apremilast treatment). Future larger studies may be needed to conclude apremilast's role in moderate-to-severe AA trying to elucidate why some patients respond while others do not.

CONCLUSION

Apremilast, an oral molecule inhibitor of PDE4, approved for the treatment of psoriasis and psoriatic arthritis, can play a role in AA treatment prescribed off-label. Although some recent clinical trials showed no efficacy of apremilast in AA, our experience reveals a good clinical response.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.