top of page
Search

Dupilumab: A Revolutionary Biologic Therapy for Atopic Dermatitis



ree

Skin plays an important role for host defence system by providing tangible barrier, innate and acquired immunity. These three levels safeguard the human body of various infectious agents and other external threats. However, breach of any level can induce an inflammatory skin disease, which partly simulates the actual protective response against infections and dangers. Clinically, it is often portrayed by itching red rashes. Skin inflammation can be the consequence of exposure to UV and ionizing radiation, allergens, pathogens or contact with chemical irritants. Chronic skin inflammation is often caused by autoimmunity disorder such as in case of alopecia areata and vitiligo  or by multifaceted interaction between genetic and environmental factors that trigger disease such as atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa (1,2).


Atopic Dermatitis: Prevalence and Mechanism of Trigger


Inflammatory skin diseases like Atopic dermatitis (AD) can be considered as one of the most common chronic skin diseases which affect children and adults worldwide. There is almost 2 to 3 fold of increase in prevalence of AD in industrialized nations that has affected approximately 15% to 20% of children and 1% to 3% of adults in the world (3).


There is an interaction of genetic and environmental factors for the manifestation and onset of AD that includes disruption of skin barrier, immune dysregulation and microbial imbalance of skin. These factors contribute to the activation of type 2 immune response with elevated levels of IL-4 and IL-13 cytokines that predominate in the acute phase of the disease.The severe urge to itch and scratch cause build up of rashes which at times can be incapacitating and detrimental to the quality of patients life and sleep (4,5).


Treatment Options for AD and their effects


Many treatment options are available for AD which are mainly designed for reinstating the disrupted skin barrier and modulating the abnormal immune response. Various alternatives such as the use of emollients, topical moisturizing agents act as a first-line therapy. Though these kinds of treatments along with sedating antihistamines reduce the frequency and severity of the itching flares helping a patient sleep better, there is not much evidence for the use of these antihistamines for extended period of time.


Management of the disease with oral corticosteroids as immunosuppressant is also widely used which contribute to the cumulative side effects for a long term use especially in children. There are many patients with moderate-to severe AD who have an inadequate response to topical treatments and immunosuppressants owing to variable efficacy and are associated with multiple adverse effects on long-term use. It is often observed patients fail to adhere to the treatment as they struggle with medication compliance or increase in their burden by routine monitoring (6).


Therefore there has been a large unmet need for safe and effective treatment for this patient population and to answer this an effective targeted biological agent Dupilumab has proved a step forward (7).


Dupilumab: Revolutionizing The Treatment For AD


Dupilumab is a fully human monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, inhibiting the signalling of both the cytokines. This causes the down-regulation type 2 inflammation in atopic dermatitis and a variety of allergic disorders including asthma (8). It helps to improve skin barrier function and healing of lesions in the skin. The patient also gets respite from unbearable itch-scratch cycle (9).


Clinical Trials and Safety


In multiple phase 3 trials, Dupilumab treated patients drastically experienced enhanced clinical signs, symptoms, and quality of life. It has an acceptable safety profile in adults and adolescents with moderate-to-severe AD. It has shown the sustained efficacy and safety up to 3 years in adults with moderate-to-severe AD enrolled in an open-label extension study. There are no clinically meaningful changes in the mean laboratory parameters ascribed to Dupilumab when adults with moderate-to-severe AD are treated up to 52 weeks and adolescents and children aged 6 months–11 years old treated up to 16 weeks (10,11). 

Achieving a clinically meaningful response within the first weeks of treatment of atopic dermatitis with Dupilumab may result in better adherence and strengthen the relationship between the health care provider and patient. Dupilumab has recently received the marketing authorization in India and is perceived as a significant milestone for treating the patients of Atopic Dermatitis. 

Indications and Dosage


Dupilumab injection is used to treat the symptoms of eczema in adults and children 6 months of age. It is available as a subcutaneous injection in the form of a pre-filled pen at doses of 200 mg and 300 mg for patients of 2+ years of age or in the form of pre-filled syringe for infants of 6+ months of age. For patients aged 6+ years, two initial loading doses are injected subcutaneously, after which, one dose every 2 or 4 weeks based on age and weight is administered. However, for patients aged 6 months to 5 years, no initial loading dose is required, and only one dose every 4 weeks based on weight is injected (12).

About the Author


Shakini Kaul Bamzai has a Master’s Degree in Biotechnology from University of Hyderabad. She has over 17 years of experience working in reputed Biotech Companies. Her first love is writing anecdotes and poems. She calls herself the SERENADE and loves hanging out with nature. She attributes her second love to amazing world of mammalian cells.  A Best Read, An Excellent Writeup and Good Food are her ingredients for the Chicken Soup for the Soul.


References


  1. Dainichi T, Hanakawa S, Kabashima K. Classification of inflammatory skin diseases: a proposal based on the disorders of the three-layered defense systems, barrier, innate immunity and acquired immunity. J Dermatol Sci. 2014;76(2):81-89.

  2. Bäsler K, Brandner JM. Tight junctions in skin inflammation. Pflugers Arch. 2017;469(1):3-14.

  3. Avena-Woods C. Overview of atopic dermatitis. Am J Manag Care. 2017;23(8 Suppl):S115-S123.

  4. Ujiie H, Rosmarin D, Schön MP, et al. Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases. Front Med (Lausanne). 2022;9:875492.

  5. Lobefaro F, Gualdi G, Di Nuzzo S, et al. Atopic Dermatitis: Clinical Aspects and Unmet Needs. Biomedicines. 2022; 10(11):2927. 

  6. Fishbein AB, Silverberg JI, Wilson EJ, et al. Update on Atopic Dermatitis: Diagnosis, Severity Assessment, and Treatment Selection. J Allergy Clin Immunol Pract. 2020;8(1):91-101.

  7. Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139.

  8. Canonica GW, Bourdin A, Peters AT, et al. Dupilumab Demonstrates Rapid Onset of Response Across Three Type 2 Inflammatory Diseases. J Allergy Clin Immunol Pract. 2022;10(6):1515-1526.

  9. Guttman-Yassky E, Bissonnette R, Ungar B, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):155-172.

  10. Lisa A. Beck, Diamant Thaçi, Mette Deleuran, Marjolein de Bruin-Weller, Zhen Chen, Faisal A. Khokhar, Meng Zhang, Zafer E. Ozturk & Brad Shumel (2022) Laboratory safety of dupilumab for up to 3 years in adults with moderate-to-severe atopic dermatitis: results from an open-label extension study, Journal of Dermatological Treatment, 33:3, 1608-1616.

  11. Paller AS, Siegfried EC, Cork MJ, et al. Laboratory Safety from a Randomized 16-Week Phase III Study of Dupilumab in Children Aged 6 Months to 5 Years with Moderate-to-Severe Atopic Dermatitis. Paediatr Drugs. 2023;25(1):67-77

  12. Dupixent. Available at: https://www.dupixent.com/atopicdermatitis/ Accessed on 12 July 2023.

Disclaimer


The matter published on this platform has been developed by independent medical writers from various healthcare backgrounds including members of MedWriters Alumni Network. Although great care has been taken in compiling and checking the information, the authors, Rxnews team and its partners or agents, and sponsors shall not be responsible or in any way liable for any errors, omissions, or inaccuracies in this blog article whether arising from negligence or otherwise, however or for any consequences arising therefrom. The inclusion and exclusion of any product do not mention that the publisher advocates or rejects its use generally or in any particular field or field. For any complaints or feedback please write to content@rxnews.in

 

Comments

bottom of page