Atopic Dermatitis (Eczema)

• Different moisturizers (either prescription or over-the-counter) have different odors and textures/consistency that may importantly influence decision-making.
• Patients with an insurance plan that covers the cost of prescription moisturizer, or those that otherwise can easily absorb the direct cost, and who place a higher value on the small potential benefits of prescription moisturizers over their costs, burdens, and lower accessibility may prefer them vs over-the-counter ones.
• Patients who have not improved sufficiently with routine use of standard over-the-counter moisturizers may prefer a trial of prescription moisturizer before adding better proven topical anti-inflammatory medications (see next recommendations).

• Resources and time to become educated, including the possibility of in-clinic demonstration, about the process and practicalities of efficiently and safely applying wet wraps.
• Location of AD lesions (sensitive areas may be more challenging or burdensome to wrap, and therefore patients may be less likely to tolerate it).
• The feasibility of wet wrap therapy fitting into the patient's schedule and daily routines.
• Those patients with more extensive disease or relapsing generalized lesions may prefer systemic therapy instead.

• Patients who value a simpler treatment routine and using less overall medication may prefer once per day application than twice per day application.
• Patients with a more severe flare or who might value resolving it more quickly may prefer twice per day application than once per day application.
• Patients who value a twice per day skin care routine, or who respond better to twice per day use, than once per day, may prefer the twice daily application.

• Adverse effects might be more prominent when applied to sensitive areas and patients might favor another therapy with larger certain benefits and less harms compared with crisaborole.
• The severity of AD - the small benefits found primarily in studies of patients with mild AD favor use only to treat mild AD flares. Conversely, its less certain and likely smaller benefits in more severe AD suggest against its use in more severe cases.
• Patients who highly value noncorticosteroid treatments might place higher value on PDE4 inhibitors over the larger and high-certainty benefits in achieving AD control and little to no harm with other treatments such as TCS or TCI.

• Patients who place a higher value on certain larger benefits and safety profile of other topical treatments (eg, TCS 2-4, tacrolimus) and certain systemic therapies are less likely to prefer topical ruxolitinib.
• Patients who are immunocompromised, immunosuppressed, or have risk factors for serious infection, cancer, thrombosis, or cardiovascular events (Table 6) may prefer other treatments compared with topical ruxolitinib.
• Patients who have not responded to other topical therapies and/or those who highly value the modest benefits of topical ruxolitinib over the more certain larger benefits of other topical treatments, and ruxolitinib's uncertain association with an increased risk of cancer, thromboembolism, serious infection, and mortality, and safety profile of systemic treatments, might favor topical ruxolitinib.

• Patients with uncontrolled AD and without serious skin infection who place a high value on avoiding polypharmacy and antimicrobial resistance will prefer to avoid adding topical antimicrobials to standard care. For severe skin infections (extent or intensity, eg, accompanied by fever or other systemic symptoms), guidance from the Infectious Disease Society of America addresses when to use systemic or topical antimicrobials.187
• Patients who are immunocompromised or immunosuppressed, have a more severe (extent or intensity) infection (particularly impetigo or ecthyma187), a history of severe infections, severe AD, or who place a high value on avoiding potential complications of bacterial skin infections may prefer adding topical antimicrobials to standard care.

• Whether the dilute bleach bath routine will fit into the patient's routine.
• The provision of clear and written instructions specific to dilute bleach baths may favor using bleach baths over not.
• The extent of a patient's open skin (cracks, fissures, excoriations) may lead to it being less tolerable by some patients, whereas other patients find it relieving.

• Patient values and preferences regarding the small magnitude of potential benefit vs the burdens and potential harms, in addition to the factors described previously.

• Young age of patient (eg, infant) and other risk factors for developing IgE-mediated food allergy would favor against pursuing an elimination diet.
• Risk for malnutrition would favor against pursuing an elimination diet.

• Allergic comorbidities that will likely be responsive to immunotherapy (eg, allergic rhinitis, or asthma with relevant sensitization) may lead to benefits for multiple diseases and therefore favor AIT.
• Values and preferences regarding SCIT vs SLIT (eg, convenience, age, travel plans).
• The plausibility of allergen sensitization to reflect allergy. For example, a patient sensitized to horse dander with no further plausible exposure to horse dander will unlikely benefit from AIT to horse. In contrast, a patient with dust mite sensitization and dust mite exposure might benefit from AIT to dust mite.

• Patients with allergic comorbidities with relevant sensitization that will likely be responsive to AIT (eg, allergic rhinitis, asthma) may be more likely to pursue this treatment even if their AD is mild if it means that multiple conditions will improve. In contrast, most individuals with mild AD and no other allergic comorbidities will likely not pursue this treatment.
• Values and preferences regarding SCIT vs SLIT (eg, convenience, age, travel plans).

Conditions to consider:

• Oral JAK inhibitors are contraindicated in pregnancy and breastfeeding: per data summarized in the drug monographs, oral JAK inhibitors increased fetal malformations (teratogenic) or fetal toxicity in drug-development animal safety studies. Baricitinib decreased male and female fertility in animals. Abrocitinib, baricitinib, and upadacitinib are excreted into milk in lactating animals (eg, upadacitinib exposure was approximately 30-fold greater in milk than in maternal plasma, of which approximately 97% of drug-related material in milk was parent drug). Direct human data addressing safety in conception, pregnancy, and breastfeeding are sparse and uncertain.
• Risk factors for adverse outcomes, including age or history of or other strong risk factors for cancer, serious infection, venous thrombosis, or cardiovascular disease, favor against JAK inhibitor use in these populations.
• Approved age differs by agent
  • Abrocitinib is FDA-approved for ages 18 years or above. Abrocitinib, however, is approved for ages 12 years or above in Canada.
  • Baricitinib is not FDA or Health Canada approved for AD. The EMA, however, approved it for AD (https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant).
  • Upadacitinib is approved for ages 12 years or above.
• Comorbidities responsive to JAK inhibitors, such as rheumatologic disease or alopecia areata, may lead to patients to favor treating multiple diseases simultaneously with one medication rather than other treatments with efficacy only for AD.
• Exceptional circumstances that clinicians and patients might consider desirable when not meeting the population criterion of another systemic treatment failing to adequately control severity of AD include the following:
  • As a brief duration bridge to one of the systemic therapies.
  • Rare and intermittent use for a severe flare (eg, erythroderma) or for social circumstances (eg, days before a major life event).

• Patients who prefer a different adverse effect profile and its required monitoring, and who can wait a longer period of time for symptom relief, may prefer azathioprine over other immunosuppressive agents. For example, although immunosuppressants are generally avoided in pregnancy, methotrexate is absolutely contraindicated and, when required, azathioprine can be used in pregnancy for treatment of systemic lupus erythematosus and inflammatory bowel disease.
• Patients with risk factors or comorbidities for harms from azathioprine (eg, liver dysfunction) or who place a high value on avoiding other harms (eg, gastrointestinal adverse effects) may place a greater value on avoiding these potential harms compared with azathioprine's possible benefits.
• The availability and value placed by patients and caregivers on other systemic treatment alternatives may influence decision making.
• Patients with comorbidities, such as rheumatologic and autoimmune diseases, may prefer to use azathioprine to address more than one condition, compared with other treatments that do not address such comorbidities.

• Cyclosporine has conventionally been administered at either low (2-3 mg/kg) or high doses (4-5 mg/kg). Whether to start at a low dose and titrate up to effect, or to start at a high dose and titrate down, depends on multiple factors, including the patient's disease severity at the time and the patient's desired rapidity of effect balanced by the increased risk of harm with higher doses. Patients should be on the lowest dose possible that achieves patient-important benefit and minimizes harms.
• The availability and/or value placed by patients/caregivers on other safer systemic treatment alternatives may influence decision-making.
• Patients with risk factors or comorbidities for harms from cyclosporine (eg, cardiovascular risk factors, difficult to control hypertension, renal dysfunction), or who place a high value on avoiding possible hypertrichosis or gum hypertrophy may place a greater value on avoiding these potential harms compared with cyclosporine's probable benefits.
• Patients should not be required to develop adverse events from cyclosporine or to first undergo a trial of it before using safer and more effective alternatives (eg, dupilumab or tralokinumab).
• Exceptional circumstances that clinicians and patients might consider desirable when not meeting the population criterion of another systemic treatment failing to adequately control severity of AD include the following:
  • As a brief duration bridge to one of the systemic therapies
  • Rare and intermittent use for a severe flare (eg, erythroderma) or for social circumstances (eg, days before a major life event).

• Patients who prefer a different adverse effect profile and its required monitoring, and who can wait a longer period of time for symptom relief, may prefer methotrexate over other immunosuppressive agents.
• Methotrexate is contraindicated in pregnancy and should not be used for patients, both male and female, intending to conceive.
• Patients with risk factors or comorbidities for harms from methotrexate (eg, liver dysfunction) or who place a high value on avoiding adverse effects (eg, stomatitis, abdominal pain) may place a greater value on avoiding these potential harms compared with methotrexate's possible benefits.
• The availability and value placed by patients and caregivers on other safer systemic treatment alternatives may influence decision making.
• Patients with comorbidities, such as rheumatologic and autoimmune diseases, may prefer to use methotrexate to address more than one condition, compared with other treatments that do not address such comorbidities.

• Patients who prefer a different adverse effect profile and its required monitoring, and who can wait a longer period of time for symptom relief, may prefer mycophenolate over other immunosuppressive agents.
• Mycophenolate is contraindicated in pregnancy and should not be used for patients intending to conceive.
• Patients with risk factors or comorbidities for harms from mycophenolate (eg, renal or liver dysfunction) or who place a high value on avoiding possible other harms (eg, gastrointestinal adverse effects) may place a greater value on avoiding these potential harms compared with mycophenolate's uncertain benefits.
• The availability and value placed by patients and caregivers on other safer systemic treatment alternatives may influence decision making.
• Patients with comorbidities, such as rheumatologic and autoimmune diseases, may prefer to use mycophenolate to address more than one condition, compared with other treatments that do not address such comorbidities.

• Patients who prefer a different adverse effect profile, or to avoid immunosuppressant medications and their required monitoring (no blood monitoring in this instance), and who desire more rapid symptom relief may prefer NB-UVB over other treatments. For example, patients who are pregnant or planning to become pregnant may prefer NB-UVB.
• NB-UVB can be difficult to access, and hence, patients who must travel large distances, incur costs (eg, parking, gas, time), or face long wait times may prefer other treatments over NB-UVB.
• Patients with photoresponsive comorbidities, such as psoriasis or vitiligo, may prefer to use NB-UV-B to address more than one condition, compared with other treatments with efficacy only in AD.
• Conversely, patients who also have photosensitive conditions, photodermatoses, or risk factors or a history of skin cancer may prefer to not use phototherapy.
• Exceptional circumstances that clinicians and patients might consider desirable when not meeting the population criterion of topical treatments and a systemic treatment failing to adequately control AD include accessing NB-UVB for the patient is highly convenient and cost-effective.