Expert opinion on management of moderate-to-severe atopic dermatitis in Qatar

Figures & data

Figure 1. Flowchart representation of consensus on opinion development by modified Delphi approach.

Table 1. Overview of the responses of the expert panel to the survey questionnaire.

Survey questions	Number of responses (N = 9)	Expert panel’s responses
Q1. Based on your clinical experience, which guidelines do you prefer to follow for AD definition? American guidelines European guidelines British guidelines Others	9/9 (100%)	European guidelines
Q2. In your clinical practice, how often do you encounter adult patients with moderate-to-severe AD? 1–5% 5–10% >10% Others	7/9 (75%): AD prevalence rate in adults ranges from 1 to 5%. 8/9 (88.88%): AD prevalence rate in adolescents and children ranges from 5 to 10 and >10%, respectively.	According to the experts, the AD prevalence rate in adults ranges from 1 to 5% (75%), and in adolescents and children, it ranges from 5 to 10 and >10%, respectively (8.88%).
Q3. What signs and symptoms are essential for defining controlled AD vs. uncontrolled AD in patients? Pruritus Disturbed quality of life Eczema Recurrent flares	9/9 (100%)	Pruritus
Q4. What are the main cytokines that play a predominant role in the etiology of AD? Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-25 IL-31, IL-4, IL-5, and IL-13 IL-22 and IL-17 All of the above	9/9 (100%)	IL-31, IL-4, IL-5, and IL-13
Q5. Do you routinely use objective clinical tools to assess the severity of AD in clinical practice? Yes No If yes, which tool do you use most? EASI SCORAD IGA/PGA If no, which tool do you recommend most to be used nationally? EASI SCORAD IGA/PGA	9/9 (100%)	Yes SCORAD
Q6. Do you routinely use subjective patient-reported assessment tools to assess the severity of AD in clinical practice? Yes No If yes, which tool do you mostly use from DLQI, POEM, and pruritus NRS score? If no, which single tool do you recommend being used nationally from DLQI, POEM, and pruritus NRS score?	9/9 (100%)	Yes DLQI
Q7. Do you recommend the Atopic Dermatitis Control Tool for defining long-term disease control in AD patients? Yes No If not, why? ________________________	9/9 (100%)	Yes, for practical reasons.
Q8. Based on your clinical experience, how do you prefer to describe AD cases? Controlled vs. uncontrolled Mild/moderate/severe based on severity assessment None Other____________________________	9/9 (100%)	Other: In the first visit, the AD case is classified into mild/moderate/severe type, and in the follow-up visit, it is classified into controlled or uncontrolled type.
Q9. Based on your current practice, what is your preferred ranking sequence for systemic therapy after topical therapy or in combination with topical treatment for AD management? Cyclosporine Corticosteroids Azathioprine Mycophenolate mofetil Methotrexate Dupilumab Baricitinib Phototherapy	Rank 1 Dupilumab*—8/9 (88.9%) Cyclosporine A*—3/9 (33.3%) Azathioprine*—1/9 (11.1%) Phototherapy—2/9 (22.2%) Rank 2 sequence given to baricitinib and mycophenolate mofetil*
Q10. Based on your clinical experience, do you think education plays an important role in the diagnosis, management, and control of AD? Yes No	9/9 (100%)	Yes

AD: atopic dermatitis; DLQI: Dermatology Life Quality Index; EASI: Eczema Area and Severity Index; IGA: investigator’s global assessment; NRS: numerical rating scale; PGA: physician global assessment; POEM: patient-oriented eczema measure; SCORAD: SCORing Atopic Dermatitis.

*Disclaimer: The systemic therapy options are based on the approval/availability of medications in Qatar.

Table 2. Screening and laboratory monitoring for patients on JAK inhibitors and cyclosporine A.*

Factors to record during the initial screening	Baseline investigations	Blood pressure measurements every 2 weeks	At 4 weeks	At 3 months	At 3–6 months
Age >65 years	Complete blood count and differential blood count		Complete blood count and differential blood count	Complete blood count and differential blood count	Complete blood count and differential blood count
History of smoking	Liver and kidney function tests		Liver transaminases	Liver transaminases	Liver transaminases
History of use of oral contraceptive or hormone replacement therapy	Tuberculosis tests		Kidney function tests	Kidney function tests	Kidney function tests
Risk or history of hepatitis B or C	Hepatitis B and C panel			Lipid panel
Presence of tuberculosis, cardiovascular disease, or malignancy	Baseline lipid panel
Whether pregnant or lactating	Pregnancy test (if applicable)
Risk for or history of thromboembolism and blood clotting disorders
Vaccination status

Dose reduction/temporary cessation is to be carried out in case of hemoglobin level reducing by >2 or to <8 g/dL, absolute neutrophil count of 500–1000/mm³ on two sequential tests, or absolute lymphocyte count of 500–750/mm³ on two sequential tests, severe hepatic impairment or creatinine clearance values of 30–60 or <30 ml/min.

*JAK inhibitor and cyclosporine A monitoring and blood work must be carried out before therapy.

Table 3. Systemic therapies in children and adolescents with moderate-to-severe AD.

Systemic drugs	Children (6–11 years)	Adolescents (12–18 years)	Clinical evidence	Level of evidence
*Dupilumab (40–42)	Approved	Approved	A, D	I, expert opinion (41)
Upadacitinib (43–45)	Not approved	Approved	A, D	I, expert opinion (44)
Abrocitinib (46,47)	Not approved	Approved	A, D	I, expert opinion
Baricitinib (48–50)	Not approved	Not approved	A, D	I, expert opinion
Tralokinumab (51,52)	Not approved	Approved	A, D	I, expert opinion

A: Meta-analysis of randomized clinical trials (RCTs) and single RCTs—level of evidence I.

B: Systematic review of cohort studies, single cohort studies, RCTs of limited quality, case-control studies, single case-control study—level of evidence II.

C: Case series, case-cohort studies, or cohort studies of limited quality—level of evidence III.

D: Expert opinions.

Note: Although methotrexate, cyclosporine A, azathioprine, and mycophenolate mofetil are not approved for AD in Qatar, clinical evidence for their efficacy in treating AD in children and adolescents is available. In some countries, cyclosporin is approved for children aged 2 years and older.

*Approved by the FDA for children aged 6 months to 5 years and approved by the EMA for children aged 6–11 years.

Table 4. Approval status, availability, and strength of the recommendation of drugs used for the treatment of AD.

List of drugs	MOA of the drugs	Approved/not approved by FDA	Approved/not approved by EMA	Approved in Qatar in AD indication	Available/not available in Qatar	Strength of recommendation
Dupilumab (40–42)	IL-4 and IL-13 inhibitor	Approved	Approved	Approved	Available	Strongly recommended (↑ ↑)
Baricitinib (48–50)	JAK inhibitor	Not approved	Approved	Not approved	Available	Can be recommended (↑)
Upadacitinib (43–45)	JAK inhibitor	Approved	Approved	Approved	Available	Can be recommended (↑)
Abrocitinib (46,47)	JAK inhibitor	Approved	Approved	Not approved	Not available	Can be recommended (↑
Tralokinumab (51,52)	IL-13 inhibitor	Approved	Approved	Not approved	Not available	Can be recommended (↑)
Cyclosporin A (53,54)	Calcineurin inhibitor	Not approved	Approved	Not approved	Available	Can be considered at the physician’s discretion (○)
Methotrexate (55,56)	Inhibits DNA and RNA synthesis and suppresses JAK/STAT pathway	Not approved	Not approved	Not approved	Available	Can be considered at the physician’s discretion (○)
Azathioprine (57,58)	Inhibits purine synthesis	Not approved	Not approved	Not approved	Available	Can be considered at the physician’s discretion (○)
Mycophenolate mofetil (59,60)	Inhibits inosine-5-monophosphate dehydrogenase	Not approved	Not approved	Not approved	Available	Can be considered at the physician’s discretion (○)
Systemic glucocorticosteroids with a follow-up plan in exceptional cases	Inhibits inflammation-associated molecules	Not approved	Not approved	Not approved	Available	Can be recommended (↑)
Systemic glucocorticosteroids without follow-up plan/>7 days	Inhibits inflammation-associated molecules	Not approved	Not approved	Not approved	Available	Not recommended (↓)
Ustekinumab SC	IL-12 and IL-24 inhibitor	Not approved	Not approved	Not approved	Not available	Not recommended (↓)

Anti-IgE: anti-immunoglobulin E; IgE: immunoglobulin E; IL-12: interleukin 12; IL-24: interleukin 24; JAK: Janus-kinase; MOA: Mechanism of Action; PO: by mouth; SC: subcutaneously; STAT: signal transducer and activator of transcription.

Figure 2. Comprehensive algorithm for the treatment of AD in adults.

Table 5. Strength of recommendation, wording, symbol, and interpretation.

Strength of recommendation	Wording as per guidelines	Symbol	Interpretation
Strongly recommended	We recommend	↑ ↑	All experts are strongly in favor of the usage of the drug.
Can be recommended	We recommend with caution	↑	All experts are in favor of the usage of this drug while considering the specific baseline and monitoring requirements.
Can be considered at the physician’s discretion	We suggest	○	Most experts would decide in favor of this drug, but a substantial minority would not.
Not recommended	We recommend against	↓	All or nearly all experts would decide against the drug.

Table

Expert opinion The experts approved the European guidelines for defining AD, particularly for patients in Qatar. Pruritus should be considered an essential feature in the diagnosis of AD. The interleukins, IL-4, IL-13, and IL-31, along with some other cytokines related to innate and adaptive immunity, and genetic modification in filaggrin play a predominant role in AD pathogenesis. The SCORAD index may be recommended as an objective clinical tool for the assessment of AD severity. The favored tool to evaluate the effect of AD on patients’ QoL was the DLQI. An efficient method to measure the long-term control of AD was the use of ADCT and ADCT was also preferred for follow-up during AD management. In the first visit, a case of AD may be classified as mild/moderate/severe, and in the follow-up visit, the same case may be classified as controlled or uncontrolled. Dupilumab is endorsed as an approved, disease-modifying agent in patients with moderate-to-severe AD who do not respond to topical treatment or systemic therapies. Although other systemic immunosuppressants, such as JAK inhibitors and tralokinumab, can be recommended, it is up to the physician’s discretion to recommend other potential off-label drugs, such as CSA, methotrexate, azathioprine, or phototherapy. Topical proactive therapy with glucocorticosteroids or calcineurin inhibitors is recommended in mild AD, and also as an adjuvant in the treatment of moderate-to-severe AD. The experts agreed on the value of therapeutic patient education, relaxation methods, and stress relief for AD management.

Summary of product characteristics abrocitinib [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf

 Google Scholar

Prescribing information of abrocitinib [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213871s000lbl.pdf

 Google Scholar

Tralokinumab prescribing information [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761180Orig1s000lbl.pdf

 Google Scholar

Summary of product characteristics of tralokinumab [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/adtralza-epar-product-information_en.pdf

 Google Scholar

Prescribing information of cyclosporin [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050715s027,050716s028lbl.pdf

 Google Scholar

Summary of product characteristics of cyclosporin [Internet]. Available from: https://www.ema.europa.eu/en/documents/referral/sandimmun-neoral-article-30-referral-annex-iii_en.pdf

 Google Scholar

Methotrexate tablet [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/008085s066lbl.pdf

 Google Scholar

Summary of product characteristics of methotrexate [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/jylamvo-epar-product-information_en.pdf

 Google Scholar

Product monograph of azathioprine [Internet]. Available from: https://pdf.hres.ca/dpd_pm/00059993.PDF

 Google Scholar

Summary of product characteristics of azathioprine [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/jayempi-epar-product-information_en.pdf

 Google Scholar

Mycophenolate mofetil capsules [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050722s021,050723s019,050758s019,050759s024lbl.pdf

 Google Scholar

Summary of product characteristics of mycophenolate mofetil [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/mycophenolate-mofetil-teva-epar-product-information_en.pdf

 Google Scholar

Data availability statement

No underlying data were collected or produced for this manuscript.