Therapeutic: abrocitinib for atopic dermatitis

4-Feb-2022

Atopic dermatitis (AD) is a chronic skin condition; patients experience inflammation of the skin and defects in the skin barrier

A dysregulated immune response contributes to the inflammation, with lesions characterised by erythema and itching; in more severe cases, the skin can become thick and leathery, papules can form and the skin might ooze and crust.

One of the most common inflammatory skin diseases, up to one in 10 adults are thought to be affected and about a third of those experience moderate to severe disease.

Historically, treatment relied on topical steroids; but, more recently, drug therapies have been introduced. Abrocitinib, developed by Pfizer, is a selective inhibitor of Janus kinase 1 (JAK1). This is believed to modulate several of the cytokines involved in the pathophysiology of atopic dermatitis, including interleukins 4, 13, 22 and 31, and thymic stromal lymphopoietin.

Several clinical trials have shown its ability to control the symptoms of atopic dermatitis. In a randomised, double-blind, placebo-controlled Phase III trial, patients with moderate to severe AD were given 100 or 200 mg of abrocitinib once a day, a 300 mg subcutaneous injection of dupilimab every 2 weeks or a placebo with background topical therapy.1

After 16 weeks, the respective proportions of subjects achieving patient-oriented eczema measure (Poem) scores of less than 3 was 11.7%, 21.3%, 12.4% and 4.8%. Improvements in night-time itching severity were similar, with the best results achieved with the higher dose of abrocitinib; the results for the lower dose and dupilimab were less good by comparison, as were the placebo scores.

Improvements were also seen in an analysis of three Phase III trial results in adolescent patients.2 Subjects were given 100 or 200 mg of abrocitinib or a placebo, either with or without supplementary topical therapies.

After 12 weeks, more adolescents given the drug at either level had a significant improvement in patient-reported results from baseline across several different measures. This included less sleep loss and improvements in quality of life.

Because symptoms can come and go, treatment flexibility is required and so the maintenance of response to the drug was assessed with continuous treatment, dose reduction or withdrawal, along with the response to returning to treatment after a flare.

Patients with moderate to severe disease who had responded to abrocitinib treatment (200 mg) were given 100 mg, 200 mg or a placebo in a blinded fashion for 40 weeks; those with disease flares were given rescue treatment in the form of 200 mg of abrocitinib plus topical therapy.3 Overall, most who continued with the drug had no disease flares and rescue treatment was effective at recapturing the response for those who did have them.

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References

  1. J.P. Thyssen, et al., J. Eur. Acad. Dermatol. Venereol. (2021): epub ahead of print (doi: 10.1111/jdv.17813).
  2. M.J. Cork, et al., J. Eur. Acad. Dermatol. Venereol. (2021): epub ahead of print (doi: 10.1111/jdv.17792).
  3. A. Blauvelt, et al., J. Am. Acad. Dermatol. 86, 104 (2022).

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