特应性皮炎的局部治疗加拿大共识指南（2025）

ABSTRACT

Introduction : Atopic dermatitis (AD) is a highly prevalent disease in Canada with signifi‑ cant patient burden. Treatment guidance for topical therapy (the mainstay of AD manage‑ ment), with particular consideration of emerg‑ ing treatments, may further improve patient

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s13555-025-01386-2 .

M.J.Gooderham $(\triangleright\triangle)$ SKiN Centre forDermatology, 775 Monaghan Rd, Peterborough, ONK9J5K2, Canada e-mail: mgooderham@centrefordermatology.com

M.J.Gooderham Probity Medical Research, Peterborough, ON, Canada

M.J.Gooderham Queen’s University, Peterborough, ON, Canada

H.C.Hong· H.Lui Department ofDermatology andSkin Science, University ofBritish Columbia, Vancouver, BC, Canada

H.C.Hong Probity Medical Research, Surrey, BC, Canada

C.Lynde Lynde Institute forDermatology, Markham, ON, Canada

C.Lynde Probity Medical Research, Markham, ON, Canada

care. Here, we aim to provide healthcare pro‑ fessionals with AD treatment recommendations from the perspective of 10 Canadian dermatolo‑ gists with expertise in managing AD.

Results : The panel collectively developed six generally accepted principles, 10 consensus

Methods : The panel of dermatologists con‑ ducted a systematic literature review and lever‑ aged their clinical experience to develop gener‑ ally accepted principles, consensus statements, and a treatment algorithm using an iterative consensus process.

K.A.Papp· I.Turchin Probity Medical Research, Waterloo, ON, Canada K.A.Papp· J.Yeung· Y.Miller‑Monthrope Division ofDermatology, Temerty School ofMedicine, University ofToronto, Toronto, ON, Canada K.A.Papp Alliance Clinical Research, Waterloo, ON, Canada J.Yeung· Y.Miller‑Monthrope Women’s College Hospital, Toronto, ON, Canada J.Yeung Probity Medical Research, Toronto, ON, Canada H.Lui Vancouver Coastal Health Research Institute, Vancouver, BC, Canada J.Ringuet Centre de Recherche Dermatologique du Québec Métropolitain, QuebecCity, QC, Canada

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statements, and a treatment algorithm. The guid‑ ance notes that assessment of disease severity should encompass both physician-rated meas‑ ures and patient-reported outcomes. Disease education, lifestyle-based strategies (e.g., trig‑ ger avoidance), and supportive measures (e.g., moisturizers) can help reduce signs and symp‑ toms of AD. Choice of therapy should consider disease-, patient-, and treatment-related factors. Although topical corticosteroids (TCS) are often used as first-line treatment in AD, they should be limited to intermittent short-term use. Non‑ corticosteroid topical therapies (e.g., topical cal‑ cineurin inhibitors; topical phosphodiesterase-4

inhibitors; and topical Janus kinase inhibitors) can be used for widespread involvement of AD according to approved use. Once treatment goals are achieved, noncorticosteroid topical mainte‑ nance therapy should continue to prevent flares and reduce the need for TCS.

Conclusion : Guidance reflecting the ben‑ efits and limitations of topical AD treatments in conjunction with patient understanding of treatment goals supports robust shared decisionmaking in the management of AD.

J.Ringuet McGill University, Montreal, QC, Canada I.Turchin Brunswick Dermatology Center, Fredericton, NB, Canada I.Turchin Department ofMedicine, Dalhousie University, Halifax, NS, Canada V.H.Prajapati Division ofDermatology, Department ofMedicine, University ofCalgary, Calgary, AB, Canada V.H.Prajapati Section ofCommunity Pediatrics, Department ofPediatrics, University ofCalgary, Calgary, AB, Canada V.H.Prajapati Section ofPediatric Rheumatology, Department ofPediatrics, University ofCalgary, Calgary, AB, Canada V.H.Prajapati Dermatology Research Institute, Calgary, AB, Canada V.H.Prajapati Skin Health andWellness Centre, Calgary, AB, Canada V.H.Prajapati Probity Medical Research, Calgary, AB, Canada

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Graphical Abstract:

Melinda. Gooderham - H. Chih-ho Hong-Charles Lynde - Kim A. Papp JensenYeung-HarveyLui-Yvettemiller-monthrope-JulienRinguetIrina Turchin- Vimal H. Prajapati

 The graphical abstract represents the opinion of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text onling $\copyright$ e authors. CC-BY-NC 2025

Keywords: Atopic dermatitis; Janus kinase inhibitor; Phosphodiesterase-4 inhibitor; Topical calcineurin inhibitor; Topical corticosteroid

|keySummaryPoints| |---| |bycarro outtbisstudy?| |atopicdermatitisisprimarilytreatedwith| |topicaltherapy,andguidanceontheuse of| |newandemergingtreatmentsmayfurther| |improvepatientcare.| |rhestudyaskedhow panel 10canadian| |dermatologistsithexpertise inmanaging| |atopic dermatitiswould proposemanaging| |the disease.| |wbatwas learned fromthe study?| | thepanelprovidedgenerallyaccepted principles, consensusrecommendations, and | |treatmentalgorithmfor the management| |of atopicdermatitisthatt reflectthee changing| |atopicdermatitis treatmentlandscape.| || | Healthcareprovidersillbebetterprepared to assessdiseaseseverityiipatients | |atopicdermatitisanduse recently| |expandedrepertoire口ftopicaltreatments立工了| |conjunctionithothersupportive:measures| |to optimizepatienttherapy.|

DIGITAL FEATURES

This article is published with digital features, including a graphical abstract to facilitate under‑ standing of the article. To view digital features for this article go to https://doi.org/10.6084/m9. figshare.28573703 .

INTRODUCTION

Atopic dermatitis (AD) is a chronic and relaps‑ ing immune-mediated inflammatory disease of the skin characterized by intense pruritus and typical eczematous morphology, including

erythema, edema, excoriation, lichenification, oozing/crusting, and/or xerosis [ 1 ]. Signs and symptoms typically begin in infancy or child‑ hood and may continue into or first appear in adulthood [ 2 – 4 ]. AD can negatively affect sleep, mental health, and quality of life (QoL) [ 5 , 6 ]. In Canada, the prevalence of AD is approximately $15\%$ for children and $4\%$ for adults, with the majority of patients having mild-to-moderate disease severity [ 7 , 8 ].

Optimal management of AD involves assess‑ ment of disease burden, education, and non‑ pharmacologic flare-mitigating measures that are most often accompanied by topical therapy and sometimes systemic therapy [ 9 – 11 ]. It has become necessary to revisit these topics given recent changes in the treatment landscape (e.g., approval of topical therapies that inhibit phos‑ phodiesterase-4 [PDE-4i] [ 12 ] and Janus kinase [JAKi] [ 13 ]) to ensure adequate guidance.

Here, we provide generally accepted princi‑ ples, consensus recommendations, and a prac‑ tical treatment algorithm for the management of AD, as developed by a panel of 10 Canadian dermatologists with expertise in managing AD.

METHODS

A panel of 10 Canadian dermatologists with sub‑ stantial clinical and research experience in AD participated in an iterative consensus process for the development of generally accepted prin‑ ciples, consensus statements, and a treatment algorithm.

At a meeting in November 2022, the full panel convened to propose themes, clinical questions, and population, intervention, control, and out‑ comes (PICO) terms that would guide a subse‑ quent literature review. A literature review was then conducted that aimed to address the ques‑ tion “What is the disease burden in patients with AD treated with topical therapies?”, includ‑ ing the characterization of disease burden before topical therapies were used (Supplementary Material Table1). It also aimed to address the question “How should treatment algorithms be modified to incorporate new topical therapies for AD?” with a focus on new treatments or

those for which fewer data were available during the development of the 2023 American Acad‑ emy of Dermatology guidelines (Supplementary Material Table2).

A subset of the full panel of dermatologists (MJG, HCH, CL, KAP, and JY) used data extracted from the literature search and expert opinion to draft, validate, and refine generally accepted clinical principles, consensus statements, and a treatment algorithm. This process occurred at a meeting in June 2023, with further refinement occurring asynchronously among the five sub‑ panel members; a survey was used to categorize statements as generally accepted principles or consensus statements.

At an in-person meeting in September 2023 consisting of the full 10-member panel, gen‑ erally accepted principles were discussed, and the final consensus statements and treatment algorithm were voted on using an iterative con‑ sensus process. Voting occurred according to a 5-point Likert scale (1, “strongly disagree”; 5, “strongly agree”), with $\geq75\%$ agreement (i.e., mean Likert score $\ge3.75$ out of 5) required to reach consensus.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

RESULTS AND DISCUSSION

Literature Search and Expert Statements

The first question (“What is the disease burden in patients with AD treated with topical thera‑ pies?”) resulted in 33 sources for data extraction. Findings helped inform the practical assessment of disease severity based on clinical and patientoriented characteristics. The second question (“How should treatment algorithms be modified to incorporate new topical therapies for AD?”) resulted in 111 sources for data extraction. Find‑ ings informed clinical practice and treatment considerations, particularly for newer topical therapies, such as topical JAKi and topical PDE4i. Following discussions and an iterative con‑ sensus process, six generally accepted principles

(Table 1 ) and 10 consensus statements (Table 2 ) were adopted. The final treatment algorithm (Fig. 1 ) had a level of agreement of $94\%$ .

Assessment of Disease Burden

Disease burden is a function of the clinical severity of AD in terms of visibly apparent skin pathology as well as patient-centric features, such as the frequency and severity of skin itch and pain, and the resulting effects on QoL (e.g., sleep; mental health burden; and school/work productivity) [ 5 , 6 ]. Quantitative AD-validated assessment tools may help healthcare provid‑ ers assess disease severity and engage in shared decision-making with the patient about treat‑ ment options. Body surface area (BSA) is a basic metric used for quantifying disease extent. The Eczema Area and Severity Index (EASI) (range, 0–72 [higher score indicates greater severity]), which has been validated in patients with AD, considers morphologic skin pathology (ery‑ thema; induration/edema/papulation; excoria‑ tions; and lichenification) and is weighted by BSA and body region [ 14 ]. The Investigator’s Global Assessment (IGA) has a 5-point scale (range, 0–5 [higher score indicates greater sever‑ ity]) based on the overall appearance of morpho‑ logic skin features (e.g., erythema; papulation; lichenification; and oozing/crusting) and has been validated in patients with AD [ 15 ].

Patient-reported outcomes validated in AD assess patient-centric perspectives on disease severity. The Dermatology Life Quality Index (DLQI) is a 10-question patient questionnaire about itch/pain, daily activities, and QoL impact (range, 0–30 [higher score indicates greater impairment]) [ 16 ]. The DLQI has been validated in patients with AD and other dermatologic dis‑ eases [ 16 ]. The Patient-Oriented Eczema Meas‑ ure (POEM) is an AD-validated assessment tool with seven questions that consider itch, sleep disturbance, and characteristics of affected skin (range, 0–28 [higher score indicates greater severity]) [ 17 ]. Numerical rating scales (NRS) have been developed to assess itch [ 18 ] and sleep disturbance [ 19 ] in AD (range, 0 [no itch or no sleep loss due to AD] to 10 [worst itch or did not sleep at all]).

Table1 Generally accepted principles for AD

|Statement|| |---|---| |Disease burden|| | Clinical disease severity in patients with AD can be assessed by BSA, EASI, and IGA. In addition, the patient perspective can be assessed by DLQI, POEM, pruritus NRS, and sleep disturbance || ||| |Treatment considerations|| | Consider patient’s preference, age, sensitive areas, disease extent, chronicity, severity, and patient-reported symptoms when evaltating treatment options for AD || ||| |It is important to involve the patient with AD in therapeutic decisions|| |Low AD disease activity may impact QoL|| | Maintenance therapy Maintenance therapy is an esenial prt fthe management ofpatient with AD || ||| |safety|| ||| |Noncorticosteroid topical therapies are generally not recommended for the treatment of AD in patients who are pregnant||

AD atopic dermatitis, BSA body surface area, DLQI Dermatology Life Quality Index, EASI Eczema Area and Severity Index, IGA Investigator’s Global Assessment, NRS numerical rating scale, POEM Patient-Oriented Eczema Measure, QoL quality of life

Scoring Atopic Dermatitis (SCORAD) is an AD-validated assessment tool that incorporates both objective physician-rated signs (extent of BSA; intensity of erythema, edema/papulation, oozing/crusting, excoriation, lichenification, and dryness [scale of 0–3]) and patient-reported symptoms (pruritus and sleep loss [scale of 0–10]) of AD; the total score ranges from 0 to 103 [ 20 ].

Although patient-centric scores can be used to serially assess changes in disease severity over time and in response to treatment, open-ended questions may be a more practical alternative in the clinic [ 21 ]. Assessment of disease severity should encompass both physician-rated meas‑ ures and patient-reported outcomes because of potential for significant QoL impact even in patients displaying milder apparent disease activity, especially among those with involve‑ ment of more visible or sensitive areas (e.g., scalp; face/neck; hands/feet; genitals) [ 21 ]. Although the above assessment tools are com‑ monly used in clinical trials, BSA, IGA, and pru‑ ritus NRS are the most practical for assessing

disease severity in routine clinical practice [Con‑ sensus Statement1 (Table 2 )] [ 22 ].

Nonpharmacologic Therapy

Education about the disease and lifestyle-based strategies, such as trigger avoidance, can help reduce signs and symptoms of AD [ 23 ]. Mois‑ turizers have been recommended for daily use (often multiple times per day and especially after bathing) to support and restore the skin’s bar‑ rier function and prevent flares [ 9 , 10 , 24 ]. Bath‑ ing practices, such as baths containing a dilute concentration of bleach, have been previously suggested as an adjunctive therapy for AD [ 9 ], but their benefits are not supported by strong evidence (Consensus Statement2). Therefore, bleach baths are not routinely recommended.

Wet wraps involve the use of wet dressings to prevent excoriation, improve skin hydration, and enhance skin penetration of topical thera‑ pies (usually lower potency topical corticos‑ teroids [TCS]) during exacerbations; they are

Table2 Consensus statements for AD

|Statement|||| |---|---|---|---| ||agreement, Likert score||| |Disease burden|Disease burden||| |1. For routine clinical practice, BSA, IGA, and pruritus asessment are the most practical|98|4.9(0.3)|| |dhisease severity meastures in patients with AD|||| |Bleach baths, wet wraps, and moisturizers|||| |2. Bleach baths have been used as an adjunctive therapy for AD, but their benefits are|94|4.7(0.6)|| |3. Although wet wraps may be helpful for extensive or recalcitrant AD, they are impractical for 96|||| |routine use||4.8(0.4)|| |Topical therapies|||| | 4. TCS in AD should ideally be limited to short-term use. If there is insufficient response after 90 4 weeks of treatment, consider alternative herapeutic options ||4.5(0.5)|| | 5. Noncorticosteroid topical therapies can be used for widespread involvement of AD according to approved use ||90 4.5(0.5)|| ||||| | 6. Topical JAKi do not have the same risk profile as TCS in AD and may be used continuously for extended periods on all sites, including sensitive areas |98||4.9(0.3)| |7. Treatment with TCS, TCI, topical PDE-4i, or topical JAKi is not advised in patients with|||| ||||4.6(0.5)| | AD who have an active skin infection unles they are receiving appropriate antimicrobial therapy |||| |8. Offlabel use of topical therapy in AD may be necessary to achieve the desired treatment|||| |outcomes|98||4.9(0.3)| ||80|4.0(1.5)|| | 9. Topical JAKi can be used concomitantly with biologic therapies in the treatment of AD 10. The thresholds for considering phototherapy and systemic therapies for AD may shift as a ||4.6(0.7)|| |wider disease spectrum may be amenable to treatment with novel noncorticosteroid topical|||| |therapies||||

AD atopic dermatitis, BSA body surface area, IGA Investigator’s Global Assessment, JAKi Janus kinase inhibitors, PDE-4i phosphodiesterase-4 inhibitors, TCI topical calcineurin inhibitors, TCS topical corticosteroids a The Likert scale ranges from 1 to 5, with higher scores indicating more agreement

generally considered safe [ 25 ]. Although wet wraps may be helpful for extensive or recalci‑ trant AD [ 26 ], they are impractical for routine use (Consensus Statement3) because substan‑ tial time and effort are required for implemen‑ tation and patients and/or their caregivers must be carefully educated on their proper use [ 10 ].

Considerations for Pharmacologic Therapy

If supportive measures do not control disease, pharmacologic interventions are advised [ 9 , 10 ]. The choice of therapy should consider disease-related factors (severity; extent; dis‑ tribution [e.g., involvement of visible and/

 Fig.1 Algorithm for the topical therapy of AD in children, adolescents, and adults. a Sensitive areas include the face (eyelids and perioral region), neck, axillary/inguinal region, and genital region. b Cochrane review has shown that QD application of TCS is as effective as BID application of TCS. c Ruxolitinib ( $1.5\%$ cream) can be resumed at the first sign of recurrence and stopped 3days after signs/symptoms have resolved. AD atopic dermatitis, BID twice daily, BSA body surface area, QD once daily, TCI topical calcineurin inhibitor, TCS topical corticosteroid, TJAKi topical Janus kinase inhibitor, TPDE-4i topical phosphodiesterase-4 inhibitor

or sensitive areas]; chronicity; symptoms), patient-related factors (age; impact on QoL; preference), and treatment-related factors (effi‑ cacy; safety; convenience; access; cost). Topical therapies are the mainstay of AD treatment, as they are generally considered safe and effective [ 10 , 27 ].

It is important to involve the patient with AD in therapeutic decisions. A mutual defini‑ tion of treatment goals should be decided by the patient and healthcare provider and periodically reevaluated.

Topical Therapies

TCS have low-, medium-, high-, and very highpotency formulations. High- and very highpotency TCS are the most efficacious of the topi‑ cal therapies, but carry a greater risk of adverse events (AEs) [ 10 , 28 , 29 ]. AEs may include local cutaneous AEs, such as atrophy, striae, and hypopigmentation (more commonly in patients with darker skin tones), as well as rare systemic AEs, such as adrenal insufficiency (due to hypo‑ thalamic–pituitary–adrenal axis suppression) if sufficient systemic absorption occurs [ 28 ]. Cor‑ ticosteroid addiction/withdrawal is a possibility but is most often associated with extended use of high-potency formulations [ 30 , 31 ]. Given these risks, TCS in AD should ideally be limited to intermittent short-term use (Consensus State‑ ment4) [ 10 ].

Noncorticosteroid topical therapies (Table 3 ) can be used for widespread involvement of AD (including on sensitive skin) according to approved use (Consensus Statement5) and do

not carry the risk of causing the corticosteroidinduced AEs listed above [ 12 , 32 , 33 ]. Topical calcineurin inhibitors (TCI) are one such non‑ corticosteroid alternative and include tacrolimus $(0.03\%$ and $0.1\%$ ointment) and pimecrolimus ( $1\%$ cream), which are approved for second-line use for moderate-to-severe and mild-to-moderate disease, respectively [ 32 , 33 ]. Tacrolimus $0.1\%$ ointment has comparable efficacy to mediumpotency TCS, and tacrolimus $0.03\%$ ointment and pimecrolimus $1\%$ cream are compara‑ ble to low-potency TCS [ 29 ]. AEs may include local stinging and/or burning (approximately $20–58\%$ of patients for tacrolimus, and $8–28\%$ of patients for pimecrolimus in some studies) [ 34 – 36 ]. Although rare cases of skin cancer and lymphoma have also been reported with TCI, a causal relationship has not been established [ 32 , 33 ], and this risk has not been substanti‑ ated by recent long-term analyses [ 37 , 38 ]. A boxed warning about these malignancies has since been removed for tacrolimus ointment and pimecrolimus cream in Canada [ 32 , 33 ].

Topical PDE-4i are another noncorticoster‑ oid alternative. Crisaborole ( $2\%$ ointment) is approved for mild-to-moderate AD [ 12 ]. Effi‑ cacy relative to vehicle was modest in phase3 studies [ 36 , 39 ]. Like TCI, AEs include stinging and/or burning (approximately $4\%$ of patients in phase3 studies [ 36 , 40 ] and $14\%$ and $32\%$ of patients in real-world studies [ 41 , 42 ]) at the application site. Roflumilast $(0.15\%$ cream) was approved in 2024 for mild-to-moderate AD in the USA [ 43 ] and approved in March 2025 in Canada [ 44 ]. It has demonstrated moderate antiinflammatory action relative to vehicle cream in phase3 studies [ 45 ].

Ruxolitinib ( $1.5\%$ cream), a topical JAKi, is another noncorticosteroid alternative for mildto-moderate AD most recently approved in Canada [ 13 ]. Efficacy was improved compared with triamcinolone acetonide ( $(0.1\%$ cream), a medium-potency TCS in a phase2 study [ 46 , 47 ]. Treatment is well tolerated, with infrequent occurrences of application site reactions [ 46 , 48 – 50 ]. The JAKi class carries a boxed warning (serious infections; malignancies; major adverse cardiovascular events [MACE]; and thrombosis [ 13 ]), which originated from data with orally administered tofacitinib when compared with

Noncorticosteroid topical therapies Table3

continued Table3

continued Table3

TCS topical calcineurin inhibitor, TCI once daily, QD phosphodiesterase-4 inhibitor, PDE-4i Janus kinase inhibitor, JAKi twice daily, BID atopic dermatitis, AD

subcutaneously administered adalimumab in adults or etanercept in adults aged $\ge50$ years with rheumatoid arthritis [ 51 – 53 ]. However, observed incidences of such events in phase3 studies of ruxolitinib ( $(0.75\%$ and $1.5\%$ cream) were not increased and were generally compa‑ rable to the overall AD population [ 48 ]; serious infections, MACE, or thromboses have not been found in the first year following its US approval [ 54 ]. Since topical JAKi do not have the same risk profile as TCS in AD, they may be suitable for continual use over extended periods on all sites including sensitive areas for this chronic disease (Consensus Statement6).

Additional considerations are necessary when using topical therapies for the treatment of patients with AD who are pregnant or breast‑ feeding. Noncorticosteroid topical therapies are generally not recommended for the treatment of patients with AD who are pregnant or breast‑ feeding, largely because of lack of data regarding potential risks [ 12 , 13 , 32 , 33 ]. However, their use may be justified in some cases [ 55 ].

Treatment with TCS [ 56 ], TCI [ 32 , 33 ], topical PDE-4i [ 36 ], or topical JAKi [ 13 ] is not advised in patients with AD who have an active skin infection unless they are receiving appropriate concomitant antimicrobial therapy (Consensus Statement7).

Initial Therapy

Initial therapy of mild-to-moderate AD should begin with low- or medium-potency TCS once daily (QD) or twice daily (BID) on affected body areas until visible skin findings have resolved. In sensitive areas, a low-potency TCS should be used QD or BID.

First-line treatment of severe AD should begin with medium- or high-potency TCS until disease severity has improved or the rec‑ ommended duration of treatment has been reached. In sensitive areas, medium- or highpotency TCS should be avoided. For TCS, QD may be equally as effective as BID dosing [ 57 ]. Liberal, as-needed use of emollients should accompany therapy [ 58 ]. Specific best practices for emollient use have been discussed previ‑ ously [ 11 ]. Other treatments may be used when

TCS are not desired because of potential risks or when AD is not adequately controlled or patients are intolerant to TCS.

TCI are often second line with the spe‑ cific drug and concentration depending on patient age, according to the label (Fig. 1 ). Tacrolimus has been approved in patients aged 2–15years $(0.03\%$ ointment BID) and patients aged≥16years $(0.1\%$ ointment BID) [ 32 ]. Pime‑ crolimus ( $1\%$ cream BID) has been approved in patients aged≥3months [ 33 ]. After TCI, other therapies may be used. Crisaborole ( $2\%$ ointment BID) is approved in patients aged $\geq3$ months [ 12 ], and ruxolitinib $(1.5\%$ cream BID) is approved in Canada for use in patients aged≥12years [ 13 ]. These therapeutic options are recommended on the basis of their effectiveness and clinical experience and are in alignment with their indicated ages for use and line of use [ 12 , 13 , 32 , 33 ].

Emergence of treatment-related AEs dur‑ ing management or the inability to achieve treatment goals by 6weeks (or 4weeks for TCS [Consensus Statement4]) may necessi‑ tate adjusting current treatment or switching to or adding another treatment (topical ther‑ apy, phototherapy, or systemic therapy) or a combination of these. In cases of inadequate response, lack of adherence, environmental triggers, infection, and competing diagnoses should first be excluded as reasons for nonre‑ sponse [ 9 ].

When modifying treatment, off-label use of topical therapy in AD may be necessary to achieve the desired treatment outcomes (Con‑ sensus Statement8). For instance, tacrolimus ( $0.1\%$ ointment) may be needed to control dis‑ ease in children aged 2–15years [ 59 ]. Clinical experience suggests that topical JAKi can be used concomitantly with systemic biologics in the treatment of AD [ 60 ] (Consensus Statement9), despite the combination being a limitation of use in the label [ 13 ].

Although treatments beyond topical therapies may be needed for refractory cases, the thresh‑ old for considering phototherapy and systemic therapies for AD may shift toward topical thera‑ pies as a wider disease spectrum may be amena‑ ble to treatment with novel noncorticosteroid topical therapies (Consensus Statement10) [ 61 ].

Maintenance Therapy

If the goal of initial therapy is achieved, main‑ tenance therapy should continue beyond com‑ plete resolution to prevent flares and reduce the need for TCS. Maintenance therapy is an essential part of the management of patients with AD; twice-weekly application of a topical anti-inflammatory agent will likely reduce the incidence of flares [ 9 , 10 , 48 , 62 , 63 ]. BID TCS should be limited to intermittent short-term use due to safety [ 10 ]. Tacrolimus $(0.03\%$ and $0.1\%$ ointment), applied QD twice per week, is indicated for maintenance therapy in patients with a high frequency of flares (e.g., at least five times per year) [ 32 ]. Ruxolitinib $(1.5\%$ cream) can be resumed at the first sign of recurrence and stopped 3days after signs/symptoms have resolved. Proactive topical therapy specifically for patients with moderate-to-severe AD has been discussed previously [ 9 , 11 ]. Patients with frequent recurrence despite maintenance ther‑ apy may be candidates for systemic therapy [ 21 ].

Limitations

The broad applicability of these guidelines may be limited in some areas since opinions origi‑ nated exclusively from experts practicing in Canada.

CONCLUSIONS

The management of AD continues to evolve. Assessment of disease severity should consider both physician-rated measures and patientreported outcomes. Emerging topical therapies focus on new targets underlying inflammation and the itch–scratch cycle. Improved clarity around the benefits, risks, and limitations of available therapies supports the development of robust treatment algorithms. Further, there is an understanding that maintenance therapy provides an opportunity to avoid disease flares and maintain patient QoL. It is important that treatment decisions for AD consider disease-,

patient-, and treatment-related factors and are based on a mutual understanding of therapeutic goals in conjunction with the patient.

Medical Writing/Editorial Assistance. Med‑ ical writing support was provided by Andrew Barszczyk, PhD, from The Curry Rockefeller Group, LLC, a Citrus Health Group, Inc., com‑ pany (Chicago, IL), and was funded by Incyte Corporation. The authors thank Christine Jean, Kaitryn Campbell, and Jean-François Dicaire from Pinnacle Marketing & Education Inc (Hud‑ son, QC, Canada) for their contributions to this initiative.

Author Contributions. Melinda J. Gooder‑ ham, H. Chih-ho Hong, Charles Lynde, Kim A. Papp, Jensen Yeung, Harvey Lui, Yvette MillerMonthrope, Julien Ringuet, Irina Turchin, and Vimal H. Prajapati contributed to the discus‑ sions, research, and validation of the gener‑ ally accepted principles and consensus state‑ ments reported in this manuscript. Melinda J. Gooderham, H. Chih-ho Hong, Charles Lynde, Kim A. Papp, Jensen Yeung, Harvey Lui, Yvette Miller-Monthrope, Julien Ringuet, Irina Turchin, and Vimal H. Prajapati critically reviewed and revised the draft manuscript for important intel‑ lectual content and approved the final version for submission.

Funding. This study and the Rapid Service Fee for this journal were funded by Incyte Cor‑ poration (Wilmington, DE, USA). Incyte had no editorial control or influence on the content of the manuscript or output from the expert panel.

Data Availability. Data sharing is not applicable to this article as no new datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest. Melinda J. Gooder‑ ham has served as a principal investigator for AbbVie, Alumis, Amgen, AnaptysBio, Apo‑ gee, Arcutis, Aristea, Aslan, Bausch Health, Boehringer Ingelheim International GmbH, Bris‑ tol Myers Squibb, Cara Therapeutics, Coherus

Biosciences, Dermira, Eli Lilly, Galderma SA, GlaxoSmithKline, Incyte Corporation, InMa‑ gene, JAMP, Janssen, LEO Pharma, MedIm‑ mune, Meiji, MoonLake, Nektar Therapeutics, Nimbus, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda Pharmaceuti‑ cal Company, Tarsus, UCB, Ventyx, and Vyne; a consultant for AbbVie, Amgen, Apogee, Aslan, Bausch Health, Boehringer Ingelheim Interna‑ tional GmbH, Eli Lilly, Janssen, Novartis Phar‑ maceuticals, Sanofi Genzyme, Sun Pharma, and UCB; an advisory board member for AbbVie, Amgen, Apogee, Arena Pharmaceuticals, Asana BioSciences, Aslan, Bausch Health, Boehringer Ingelheim International GmbH, Eli Lilly, Gal‑ derma SA, Incyte Corporation, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Union; and a paid speaker for AbbVie, Amgen, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim International GmbH, Eli Lilly, Galderma SA, Janssen, JAMP, LEO Pharma, L’Oréal, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB. H. Chih-ho Hong has served as a speaker, advisor, consultant, and/or investiga‑ tor for AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GlaxoSmith‑ Kline, Incyte Corporation, Janssen, LEO Pharma, Medimmune, Merck, Mirimar, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, Roche, and UCB. Charles Lynde has served as a speaker and/or consultant for AbbVie, Amgen, Aralez, Arcu‑ tis, Bausch Health, Bayer, Boehringer Ingel‑ heim, Bristol Myers Squibb, Celgene, Cipher, Dermavant, Eli Lilly, Fresnius Kabi, Galderma, GlaxoSmithKline, Incyte Corporation, Inno‑ vaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma, L’Oréal, Medexus, MedX, Merck, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharma, TEVA, Tribute, UCB, Valeant, Viatris, and Volo Health and has served as a principal investigator for AbbVie, Acelyrin, Akros, Altius, Amgen, Aralez, Arcu‑ tis, Avillion, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cell‑ trion, Cipher, Concert, Dermavant, Devonian, Eli Lilly, Evelo, Galderma, GlaxoSmithKline,

Incyte Corporation, Innovaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma, L’Oréal, Medexus, MedX, Merck, MoonLake, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharma, TEVA, Tribute, UCB, Valeant, Viatris, and Volo Health. Kim A. Papp has received honoraria and/or grants as a con‑ sultant, speaker, investigator, or scientific officer from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biop‑ harma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DICE Pharmaceuticals, DICE Therapeutics, Eli Lilly and Company, Evelo Biosciences, Forbion, Galderma, Hori‑ zon Therapeutics, Incyte Corporation, Jans‑ sen, Kymab, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, SanofiAventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab. Jensen Yeung has served as a consultant, investigator, or speaker or received honoraria from AbbVie, Amgen, Arcutis, Apogee, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galderma, Incyte Corporation, JAMP Pharma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, and UCB. Harvey Lui has served as an advisor, consultant, investigator, and/or speaker for AbbVie, Incyte Corporation, L’Oréal, Novartis, and Vita Imag‑ ing. Yvette Miller-Monthrope has served as an advisor, consultant, and/or speaker for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Fresenius Kabi, Galderma, Incyte Corporation, Janssen, Sanofi, Sun Pharma, Novartis, and UCB. Julien Ringuet has served as an advisor, consult‑ ant, and/or speaker for AbbVie, Amgen, Apogee, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte Corporation, Janssen, LEO Pharma, L’Oréal, NKS Health, Novartis, Organon, Pfizer, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB and served as an investigator for AbbVie, Alumis, Amgen, Ari‑ stea, Aslan, Bristol Myers Squibb, Celgene, Con‑ cert Pharmaceuticals, CorEvitas, DICE Therapeu‑ tics, Incyte Corporation, Innovaderm, Janssen, LEO Pharma, Merck, Pfizer, Sanofi-Genzyme,

Sun Pharma, and UCB. Irina Turchin has served as a speaker, advisor, consultant, or investiga‑ tor for AbbVie, Amgen, Arcutis, Aristea, Bausch Health, Bristol Myers Squibb, Boehringer Ingel‑ heim, Eli Lilly, Galderma, Horizon Therapeu‑ tics, Incyte Corporation, Janssen, Kiniksa, LEO Pharma, Mallinckrodt, MoonLake, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and Ventyx Biosciences. Vimal H. Prajapati has served as an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, BioScript Solu‑ tions, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Celltrion, Cipher, Concert, CorEvitas, Eczema Society of Canada, Eli Lilly, Galderma, Glaxo‑ SmithKline, Homeocan, Incyte Corporation, JAMP Pharma, Janssen, Johnson & Johnson, LEO Pharma, Medexus, Novartis, Organon, Pedi‑ apharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant; served as an inves‑ tigator for AbbVie, AnaptysBio, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvi‑ tas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte Corporation, Janssen, LEO Pharma, Meiji Pharma, Nektar Therapeutics, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, and UCB; and received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme.

Ethical Approval. This article is based on previously conducted studies and does not con‑ tain any new studies with human participants or animals performed by any of the authors.

Open Access. This article is licensed under a Creative Commons Attribution-NonCommer‑ cial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, pro‑ vide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons

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REFERENCES

1. Kirchhof MG, Landells I, Lynde CW, Gooderham MJ, Hong CH. Approach to the assessment and management of adult patients with atopic der‑ matitis: a consensus document. Section I: patho‑ physiology of atopic dermatitis and implications for systemic therapy. J Cutan Med Surg. 2018;22(1 suppl):6S-9S. 2. Garmhausen D, Hagemann T, Bieber T, etal. Char‑ acterization of different courses of atopic derma‑ titis in adolescent and adult patients. Allergy. 2013;68(4):498–506. 3. Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a general population. J Am Acad Dermatol. 1994;30(1):35–9. 4. Lee HH, Patel KR, Singam V, Rastogi S, Silverberg JI. A systematic review and meta-analysis of the prev‑ alence and phenotype of adult-onset atopic der‑ matitis. J Am Acad Dermatol. 2019;80(6):1526–32. 5. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic der‑ matitis in US adults: a population-based crosssectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–7. 6. Kwatra SG, Gruben D, Fung S, DiBonaventura M. Psychosocial comorbidities and health status among adults with moderate-to-severe atopic der‑ matitis: a 2017 US national health and wellness survey analysis. Adv Ther. 2021;38(3):1627–37. 7. Barbarot S, Auziere S, Gadkari A, etal. Epidemiol‑ ogy of atopic dermatitis in adults: results from an international survey. Allergy. 2018;73(6):1284–93. 8. Silverberg JI, Barbarot S, Gadkari A, etal. Atopic dermatitis in the pediatric population: a crosssectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417–28. 9. Chu DK, Schneider L, Asiniwasis RN, etal. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/ American College of Allergy, Asthma and Immu‑ nology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based rec‑ ommendations. Ann Allergy Asthma Immunol. 2023;132(2):274–312. 10. Sidbury R, Alikhan A, Bercovitch L, etal. Guide‑ lines of care for the management of atopic derma‑ titis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1–20. 11. Wollenberg A, Kinberger M, Arents B, etal. Euro‑ pean guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treat‑ ment recommendations for special AE patient populations. J Eur Acad Dermatol Venereol. 2022;36(11):1904–26. 12. Pfizer Canada Inc. EUCRISA ® (crisaborole). Product Monograph. Kirkland: 2021. 13. Incyte Corporation and Innomar Strategies. Opzelura ® (ruxolitinib cream). Product Mono‑ graph. Oakville: 2024. 14. Hanifin JM, Thurston M, Omoto M, etal. The Eczema Area and Severity Index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol. 2001;10(1):11–8. 15. Simpson EL, Bissonnette R, Paller AS, etal. The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): a clinical outcome measure for the severity of atopic dermatitis. Br J Dermatol. 2022;187(4):531–8. 16. Finlay AY, Khan GK. Dermatology Life Qual‑ ity Index (DLQI)—a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–6. 17. Charman CR, Venn AJ, Williams HC. The PatientOriented Eczema Measure: development and ini‑ tial validation of a new tool for measuring atopic eczema severity from the patients’ perspective. Arch Dermatol. 2004;140(12):1513–9. 18. Yosipovitch G, Reaney M, Mastey V, etal. Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol. 2019;181(4):761–9. 19. Puelles J, Fofana F, Rodriguez D, etal. Psycho‑ metric validation and responder definition of the sleep disturbance numerical rating scale in mod‑ erate-to-severe atopic dermatitis. Br J Dermatol. 2022;186(2):285–94. 20. Severity scoring of atopic dermatitis: the SCO‑ RAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23–31. 21. Simpson EL, Bruin-Weller M, Flohr C, etal. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Derma‑ tol. 2017;77(4):623–33. 22. Gooderham MJ, Bissonnette R, Grewal P, Lansang P, Papp KA, Hong CH. Approach to the assessment and management of adult patients with atopic der‑ matitis: a consensus document. Section II: tools for assessing the severity of atopic dermatitis. J Cutan Med Surg. 2018;22(1):10S-S16. 23. Heratizadeh A, Werfel T, Wollenberg A, et al. Effects of structured patient education in adults with atopic dermatitis: multicenter rand‑ omized controlled trial. J Allergy Clin Immunol. 2017;140(3):845–53. 24. van Zuuren EJ, Fedorowicz Z, Arents BWM. Emol‑ lients and moisturizers for eczema: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2017;177(5):1256–71. 25. Schoch JJ, Davis DMR. A practical guide to outpa‑ tient wet dressings for pediatric atopic dermatitis. Curr Derm Rep. 2013;2:212–5. 26. Dabade TS, Davis DM, Wetter DA, etal. Wet dress‑ ing therapy in conjunction with topical corti‑ costeroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30years at Mayo Clinic. J Am Acad Dermatol. 2012;67(1):100–6. 27. Yang YB, Gohari A, Lam J. Brief academic review and clinical practice guidelines for pediatric atopic dermatitis. Curr Pediatr Rev. 2021;17(3):229–37. 28. Broersen LH, Pereira AM, Jorgensen JO, Dekkers OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endo‑ crinol Metab. 2015;100(6):2171–80. 29. Chu DK, Chu AWL, Rayner DG, et al. Topi‑ cal treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials. J Allergy Clin Immunol. 2023;152(6):1493–519. 30. Hajar T, Leshem YA, Hanifin JM, etal. A systematic review of topical corticosteroid withdrawal (“ster‑ oid addiction”) in patients with atopic dermati‑ tis and other dermatoses. J Am Acad Dermatol. 2015;72(3):541–9.

31. Hwang J, Lio PA. Topical corticosteroid withdrawal (’steroid addiction’): an update of a systematic review. J Dermatolog Treat. 2022;33(3):1293–8. 32. LEO Pharma Inc. PROTOPIC ® (tacrolimus). Prod‑ uct Monograph. Toronto: 2022. 33. Bausch Health Canada Inc. ELIDEL ® (pimecroli‑ mus). Product Monograph. Laval: 2020. 34. Chen SL, Yan J, Wang FS. Two topical calcineu‑ rin inhibitors for the treatment of atopic der‑ matitis in pediatric patients: a meta-analysis of randomized clinical trials. J Dermatolog Treat. 2010;21(3):144–56. 35. Amiri D, Schwarz CW, Gether L, Skov L. Safety and efficacy of topical calcineurin inhibitors in the treatment of facial and genital psoria‑ sis: a systematic review. Acta Derm Venereol. 2023;103:adv00890. 36. Paller AS, Tom WL, Lebwohl MG, etal. Efficacy and safety of crisaborole ointment, a novel, non‑ steroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494–503. 37. Devasenapathy N, Chu A, Wong M, etal. Can‑ cer risk with topical calcineurin inhibitors, pime‑ crolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis. Lancet Child Adolesc Health. 2023;7(1):13–25. 38. Asgari MM, Tsai AL, Avalos L, Sokil M, Quesen‑ berry CP Jr. Association between topical calcineu‑ rin inhibitor use and keratinocyte carcinoma risk among adults with atopic dermatitis. JAMA Der‑ matol. 2020;156(10):1066–73. 39. Ahmed A, Solman L, Williams HC. Magnitude of benefit for topical crisaborole in the treatment of atopic dermatitis in children and adults does not look promising: a critical appraisal. Br J Dermatol. 2018;178(3):659–62. 40. Eichenfield LF, Call RS, Forsha DW, etal. Longterm safety of crisaborole ointment $2\%$ in children and adults with mild to moderate atopic dermati‑ tis. J Am Acad Dermatol. 2017;77(4):641–9. 41. Pao-Ling Lin C, Gordon S, Her MJ, Rosmarin D. A retrospective study: application site pain with the use of crisaborole, a topical phosphodiesterase 4 inhibitor. J Am Acad Dermatol. 2019;80(5):1451–3. 42. Ma C, Sun J, Liu Z, Zhang C. Real-world efficacy of $2\%$ crisaborole ointment on chronic hyperplasia lesions in 49 patients with atopic dermatitis. Int J Dermatol. 2024;63(10):1375–82. 43. Arcutis Biotherapeutics. ZORYVE ® (roflumilast). Full Prescribing Information. Westlake Village: 2024. 44. Arcutis Canada. ZORYVE ® (roflumilast cream). Product Monograph. North York: 2025. 45. Simpson EL, Eichenfield LF, Alonso-Llamazares J, etal. Roflumilast cream, $0.15\%$ , for atopic derma‑ titis in adults and children: INTEGUMENT-1 and INTEGUMENT-2 randomized clinical trials. JAMA Dermatol. 2024;160(11):1161–70. 46. Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572–82. 47. Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: results from a phase2, randomized, dose-ranging, vehicle- and active-controlled study. J Am Acad Dermatol. 2020;82(6):1305–13. 48. Papp K, Szepietowski JC, Kircik L, etal. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: results from two phase3 stud‑ ies. J Am Acad Dermatol. 2023;88(5):1008–16. 49. Leung DYM, Paller AS, Zaenglein AL, et al. Safety, pharmacokinetics, and efficacy of rux‑ olitinib cream in children and adolescents with atopic dermatitis. Ann Allergy Asthma Immunol. 2023;130(4):500–7. 50. Eichenfield LF, Stein Gold LF, Simpson EL, etal. A phase 3 study of ruxolitinib cream in children aged $^{2-<12}$ years with atopic dermatitis (TRuEAD3): 8-week analysis. In: Presented at 32nd Euro‑ pean Academy of Dermatology and Venereology (EADV) Congress; 2023 October 11–14; Berlin 51. US Food and Drug Administration. FDA requires warnings about increased risk of serious heartrelated events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflam‑ matory conditions. 2021. https://www.fda.gov/ drugs/drug-safety-and-availability/fda-requireswarnings-about-increased-risk-serious-heart-relat ed-events-cancer-blood-clots-and-death . Accessed Feb 2, 2024. 52. Charles-Schoeman C, Wicker P, Gonzalez-Gay MA, etal. Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor. Semin Arthritis Rheum. 2016;46(3):261–71. 53. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316–26. 54. Hu W, Thornton M, Livingston RA. Real-world use of ruxolitinib cream: safety analysis at 1year. Am J Clin Dermatol. 2024;25(2):327–32. 55. Vestergaard C, Wollenberg A, Barbarot S, etal. European task force on atopic dermatitis posi‑ tion paper: treatment of parental atopic der‑ matitis during preconception, pregnancy and lactation period. J Eur Acad Dermatol Venereol. 2019;33(9):1644–59. 56. Merck Canada Inc. DIPROSONE ® (betamethasone dipropionate). Product Monograph. Kirkland: 2017. 57. Lax SJ, Harvey J, Axon E, et al. Strategies for using topical corticosteroids in children and adults with eczema. Cochrane Database Syst Rev. 2022;3(3):CD013356. 58. van Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BWM. Emollients and mois‑ turisers for eczema. Cochrane Database Syst Rev. 2017;2(2):CD012119. 59. Kang S, Lucky AW, Pariser D, Lawrence I, Hanifin JM. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermati‑ tis in children. J Am Acad Dermatol. 2001;44(1 Suppl):S58-64. 60. Stefanko NS, Quan VL, Chovatiya R. Efficacy, safety, and treatment patterns of ruxolitinib $1.5\%$ cream in adult atopic dermatitis: a single center retrospective study. J Am Acad Dermatol. 2023;89(2):415–7. 61. Simpson EL, Kircik L, Blauvelt A, etal. Ruxolitinib cream in adolescents/adults with atopic dermati‑ tis meeting severity thresholds for systemic ther‑ apy: exploratory analysis of pooled results from two phase 3 studies. Dermatol Ther (Heidelb). 2024;14(8):2139–51. 62. Schmitt J, von Kobyletzki L, Svensson A, Apfel‑ bacher C. Efficacy and tolerability of proactive treatment with topical corticosteroids and cal‑ cineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized con‑ trolled trials. Br J Dermatol. 2011;164(2):415–28. 63. Glazenburg EJ, Wolkerstorfer A, Gerretsen AL, Mulder PG, Oranje AP. Efficacy and safety of fluti‑ casone propionate $0.005\%$ ointment in the longterm maintenance treatment of children with atopic dermatitis: differences between boys and girls? Pediatr Allergy Immunol. 2009;20(1):59–66. 64. Luger TA, Lahfa M, Folster-Holst R, etal. Longterm safety and tolerability of pimecrolimus cream $1\%$ and topical corticosteroids in adults with mod‑ erate to severe atopic dermatitis. J Dermatolog Treat. 2004;15(3):169–78. 65. Meurer M, Fartasch M, Albrecht G, etal. Long-term efficacy and safety of pimecrolimus cream $1\%$ in adults with moderate atopic dermatitis. Dermatol‑ ogy. 2004;208(4):365–72. 66. Sigurgeirsson B, Boznanski A, Todd G, et al. Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial. Pediatrics. 2015;135(4):597–606. 67. Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12-week study of tacrolimus oint‑ ment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol. 2001;44(1 Suppl):S47-57. 68. Hanifin JM, Ling MR, Langley R, Breneman D, Rafal E. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J Am Acad Dermatol. 2001;44(1 Suppl):S28-38. 69. Soter NA, Fleischer AB Jr, Webster GF, Mon‑ roe E, Lawrence I. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. J Am Acad Dermatol. 2001;44(1 Suppl):S39-46. 70. Reitamo S, Rustin M, Ruzicka T, etal. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002;109(3):547–55. 71. Reitamo S, Van Leent EJ, Ho V, etal. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis. J Allergy Clin Immunol. 2002;109(3):539–46.