November 10, 2021
A review of the current state of AD management in the MENA region
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itching and recurrent eczematous lesions. According to various secondary sources, the prevalence of AD in regions of the Middle East and North Africa (MENA) has generally been lower than in Europe and North America – the reported prevalence amongst the countries in the region ranges from 3 to 14%. Nevertheless, recent time trends show increasing AD prevalence in the developing world, including the MENA region. This upsurge is likely due to the combination of environmental, social, and economic factors. Dwelling in urban environments compared with rural settings has been linked to AD in the MENA. In addition to rising prevalence, the management of the condition remains a challenge. Treatment obtainability is inadequate in countries with low socioeconomic status, which highlights the need for enhanced access to the diagnosis and treatment strategies.
Current State of Atopic Dermatitis Treatment in the MENA Region
The emollients and moisturizers are the mainstay of treatment and offer improvement in skin barrier function and symptoms, reducing the need for prescription anti-inflammatory therapies. We want to highlight that although emollients and moisturizers offer affordable treatment options, they prove to be insufficient for moderate-to-severe cases. Besides, the greasiness/smell of moisturizer, frequent application, and adverse reactions may lead to poor adherence, and specialized emollients and prescription emollient devices can be costly.
Topical corticosteroids (TCSs) are recommended as the first-line anti-inflammatory therapy that is considered effective with a satisfactory safety profile. The therapy offers low-cost prescription therapy with several generic options. Like any other treatment option, the TCSs have a few drawbacks, such as long-term local side effects (skin atrophy and systemic side effects such as HPA axis suppression merits routine monitoring) and hypopigmentation in patients of color. Moreover, the treatment has limited use in children. TCIs such as hydrocortisone, desonide, mometasone furoate, fluticasone propionate, triamcinolone acetonide, betamethasone valerate, betamethasone dipropionate, and clobetasol propionate are available in some countries of the MENA region.
Topical calcineurin inhibitors (TCIs; pimecrolimus, tacrolimus) are effective for short- and long-term treatment of mild-to-severe AD in adults and children and are useful for sensitive areas (face, genitals, and skin folds). However, the therapy comes with a higher cost of treatment with local tolerability issues (stinging/burning), which may require patient counseling to prevent nonadherence. Moreover, the TCIs find limited use in combination with phototherapy as sun exposure should be avoided during TCI treatment. Further, it is a well-known fact that TCIs come with an FDA boxed warning for cancerogenesis. Thus, the agents are not approved in all the MENA regions. According to the analysis by DelveInsight, pimecrolimus is accessible in Egypt and various countries in the Middle East, namely Jordan, Lebanon, Oman, Qatar, Saudi Arabia, Turkey, and the United Arab Emirates. On the other hand, tacrolimus is also approved in South Africa, apart from the countries where pimecrolimus is approved.
With the approval of crisaborole topical ointment 2% (Eucrisa) – a PDE4 inhibitor – in Japan in January 2020 for mild-to-moderate AD, we can only hope for the researchers to fast-track investigations of the drug’s feasibility and tolerability in the MENA region.
Systemic therapies such as antihistamines are widely available with low side effect profiles associated with ADHD symptoms in children with AD. Systemic immunosuppressants (methotrexate and cyclosporine) are effective in moderate-to-severe cases with limited long-term use. Both methotrexate and cyclosporine are accessible in Egypt, Morocco, Nigeria, South Africa, Tunisia, Jordan, Lebanon, Oman, Qatar, Saudi Arabia, Turkey, and the United Arab Emirates. However, methotrexate is not available in Qatar.
Biologics are an effective treatment option for patients with moderate to severe AD. The approvals of the anti-IL-4Rα antibody dupilumab (2016, FDA; 2017, EMA) and, more recently, of the small-molecule Janus kinase (JAK) inhibitor baricitinib (2020, EMA) and the anti-IL-13 antibody tralokinumab (2021, EMA) have provided first-in-class representatives of different therapeutic strategies for the treatment of moderate-to-severe forms of AD. Dupixent (dupilumab) is a monoclonal antibody that inhibits interleukin (IL)–4 and IL-13 signaling by blocking the shared IL-4Ra. Dupixent is a very cost-intensive therapy approved only in UAE among the countries in the MENA region. In April 2021, it was approved in Egypt for adults and adolescents 12 years and older with moderate-to-severe AD and severe asthma by the Egyptian Drug Authority. We also look forward to more Dupixent approvals in other MENA countries in the future.
Updates on Emerging Drug Development in MENA region
The emerging pipeline for AD in the MENA region is dry. The pipeline poses a few key players investigating their products for this patient pool.
- An observational study of patients receiving Dupixent for AD in Saudi Arabia, Kuwait, Israel, and the UAE is ongoing.
- In Israel, Eli Lilly and Company is investigating its product baricitinib in a Phase III trial in moderate to severe AD patients.
- Shulov Innovate for Science is investigating its compound ZEP-3Na in a Phase II trial in subjects with mild to moderate AD in Israel.
- AbbVie is investigating its product upadacitinib in a Phase III trial combined with topical corticosteroids in adolescent and adult participants with moderate to severe AD.
- Pfizer is evaluating abrocitinib to determine the efficacy and safety of its drug with or without topical medications in subjects aged 12 years and older with moderate to severe AD.
Olumiant (baricitinib), Rinvoq (upadacitinib), and Abrocitinib (PF-04965842) are being developed in the US, EU-5, and Japan as well. Moreover, Olumiant is approved by the EMA. DelveInsight is buoyant about the approval of these drugs in the MENA region soon. However, the trials are not being conducted in all the regions thus, leading to scarcity of current and emerging treatment options in different areas of the MENA region. Additionally, most of the upcoming therapies are JAK inhibitors, which remains a concern as recently, the US FDA has issued a black box warning for certain JAK inhibitors. This news comes amid a delay in approval for multiple JAK inhibitors to treat inflammatory skin conditions. It will be interesting to see these drugs’ approval and market access globally, particularly in the MENA region.
Understanding the Burden of AD in the MENA Region
Growing AD prevalence and burden is a severe issue in the MENA region because these regions face unique challenges in delivering care to patients with AD. Although AD treatment guidelines are similar globally, in managing AD, the MENA region faces challenges that contribute to disease burden. A meaningful understanding of the burden and treatment of AD in this region is impeded by significant data gaps; therefore, an increase in research and awareness in the field is recommended. Furthermore, the region faces serious issues regarding the approval and market access of the drugs as the pricing is on the higher end, adding to the cost burden on the patients suffering from AD and their caregivers. Besides that, the emerging pipeline for AD in this region is dry, which leads to the lack of upcoming treatment options and management strategies for this patient pool.
Nevertheless, the current scenario of AD management in the MENA region holds a vast scope of further advancement with efforts to revitalize the promising and imminent opportunities in terms of approval of drugs, access, and cost!!
- (Al-Afif et al., 2019)Al-Afif, K. A. M., Buraik, M. A., Buddenkotte, J., Mounir, M., Gerber, R., Ahmed, H. M., Tallman, A. M., & Steinhoff, M. (2019). Understanding the Burden of Atopic Dermatitis in Africa and the Middle East. Dermatology and Therapy, 9(2), 223.
- Dupixent® (dupilumab) approved in Egypt for adults and adolescents 12 years and older with moderate-to-severe Atopic Dermatitis & severe Asthma by the Egyptian Drug Authority | ZAWYA MENA Edition. (n.d.)
- Home – ClinicalTrials.gov. (n.d.)
- Lopez Carrera, Y. I., Al Hammadi, A., Huang, Y.-H., Llamado, L. J., Mahgoub, E., & Tallman, A. M. (2019). Epidemiology, Diagnosis, and Treatment of Atopic Dermatitis in the Developing Countries of Asia, Africa, Latin America, and the Middle East: A Review. Dermatology and Therapy 2019 9:4, 9(4), 685–705.