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by Rod Tucker BPharm PhD
Published on 7 January 2020

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What next for dupilumab?

Biological therapy with monoclonal antibodies (biologics) has revolutionised the treatment landscape of several therapeutic areas including gastroenterology, rheumatology, immunology and chemotherapy.

Biologics have also had a significant impact in the treatment of patients with skin disorders and in particular psoriasis, which affects up to 3% of the population in the UK.

Since 2017, a biologic, dupilumab, has been introduced for the treatment of patients with moderate to severe atopic eczema (AE), a long-term and pruritic, inflammatory skin disorder that affects up to 20% of children and roughly 3% of adults. Prior to the introduction of dupilumab, treatment options for those with moderate to severe AE involved the use of systemic agents and while these are generally effective, all caused side-effects that limited their use. Dupilumab has been approved by NICE for the management of patients with moderate to severe atopic eczema who failed to respond to at least one systemic therapy or if such treatments cannot be used because of either patient intolerance or contra-indications. The drug blocks the interleukin (IL)-4 receptor subunit, which is the site of action for the cytokines IL-4 and IL-13, produced by T-helper 2 cells, both of which appear to have an important role in the initiation of the symptoms of atopic eczema. The efficacy of dupilumab has sparked much interest in the potential of other biologics for the management of moderate to severe AE and both nemolizumab (Galderma) and lebrikizumab (Dermira) are showing great promise as additional therapies and fast approaching FDA approval.1

It has also clear that IL-4 and IL-13 signalling is an important inflammatory pathway in asthma and based on the results of several studies, dupilumab has recently been granted approval by the EMA as an add-on therapy for patients with severe asthma.2

But is it possible that blockage of the IL-4,13 pathway is important in other inflammatory dermatological conditions? A recent retrospective analysis observed that dupilumab produced improvements in hand dermatitis3 and alopecia areata.4 Additionally, a case report suggested that the drug may be of value in chronic urticaria,5 as witnessed by a patient whose condition was recalcitrant to treatment with omalizumab but successfully resolved with dupilumab.

The potential role for dupilumab in the management of skin problems other than atopic eczema was the subject of a recent systematic review.6 It identified several case studies where dupilumab had been successfully used off-license, to manage a wide range of skin problems including chronic pruritus, prurigo nodularis, allergic contact dermatitis and bullous pemphigoid. The authors concluded that dupilumab appeared to be an effective treatment for these other conditions. It was also apparent from a review of the case studies, that dupilumab had been used as a last resort following the failure of multiple conventional treatments for the condition in question. Furthermore and somewhat interestingly, all of the case reports had used the dosing schedule of dupilumab that was approved for atopic eczema.

These case reports have provided the impetus for several Phase II trials examining the effectiveness of dupilumab in hand eczema, alopecia areata and chronic urticaria, all of which can be difficult to manage.

The favourable results from the diverse case studies make it increasingly apparent that the IL-4 and IL-13 inflammatory pathways are likely to predominate in a much wider range of skin conditions it is also clear that we still have some distance to travel on our journey of understanding with regard to the significance of IL-4 and IL-13 signalling. Publication of the Phase II trials will serve to offer greater clarity into the importance of these pathways in a variety of inflammatory dermatoses. But perhaps most importantly, if the results of the trials can substantiate the observations in case studies, it will offer clinicians an effective therapy to manage a broader range of skin conditions and ultimately improve disease outcomes for a larger number of patients.

References

  1. National Eczema association. Two new atopic dermatitis biologics show promising results in phase IIb clinical trials. https://nationaleczema.org/nemolizumab-lebrikizumab/ (accessed December 2019).
  2. European Medicines Agency. New add-on treatment for patients with severe asthma. www.ema.europa.eu/en/news/new-add-treatment-patients-severe-asthma (accessed December 2019).
  3. Lee N et al. A retrospective review of Dupilumab for hand eczema. [Letter]. Dermatology 2019;235:187–8.
  4. Darrigada AS et al. Dual efficacy of Dupilumab in a patient with concomitant atopic dermatitis and alopecia areata. Br J Dermatol 2018;179(2):534–6.
  5. Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria. J Allergy Clin Immunol Pract 2019;7(5):1659–61.
  6. Hendricks AJ, Yosipovitch G, Shi VY. Dupilumab use in dermatologic conditions beyond atopic dermatitis – a systematic review. J Dermatolog Treat 2019;12:1–10.


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