Case Scenario #1 Luis is a 9-year-old male seen in clinic with a complaint of worsening - PowerPoint Presentation

Case Scenario #1 Luis is a 9-year-old male seen in clinic with a complaint of worsening pruritus causing difficulties in school and sleep. History: He first complained of dry, itchy skin on the flexural areas of his arms and legs about 2 years ago. Symptoms are worse in winter.Father has asthma and perennial rhinitisPhysical examinationDry skinErythema, dryness, lichenification noted in flexural areas of both arms and legsIncreased scaling on legs noted © Professor Raimo Suhonen. Used by DermNet New Zealand with permission under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (http://creativecommons.org/licenses/by-nc-nd/3.0/nz/) with no changes.

Wide Ranging Impact of Atopic Dermatitis AD Severe AD in childhood disrupted education Sleep disturbance and daytime fatigue due to itch and pain Headaches, depression, low self-esteem Poor tolerance for heat—causes flares of AD Poor qualifications, limited career prospects, financial problems Not able to work in a full-time job Potential suicidal ideation Family holidays in warm climates impossible; limits business trips 3

Itch and Sleep Symptoms Simpson E, et al. JAMA Dermatol . 2018;154(8):903-912.NRS, numerical rating scale; PO-SCORAD, Patient-Oriented Scoring of Atopic Dermatitis

Cumulative Impact On Patients’ Lives Resulting In Life Impairment* Simpson E, et al. JAMA Dermatol . 2018;154(8):903-912.*Based on the Dermatology Life Quality Index

Impairment is Worse with AD Than Psoriasis Eckert L, et al. J Am Acad Dermatol. 2018;78(1):54-61. Data derived from the 2013 US National Health and Wellness Survey, a real-world survey of adults with and without a self-reported diagnosis of AD in the USAD self-reports were propensity matched with non-AD controls and with psoriasis controls. Work Productivity and Activity Impairment, US

Recommendations for Assessing Disease Severity Commonly assessed based on Body surface areaLocation, distributionOther tools are available but not commonly used in practiceEASI, POEM, SCORADDLQIBest practice: Combine clinical tools with patient interview questions to assess impact of AD on daily functioning and quality of lifeCharman CR, et al. Arch Dermatol. 2004;140(12):1513-1519. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351.Rehal B, et al. PLoS One. 2011;6(4):e17520.Finlay AY, et al. Clin Exp Dermatol . 1994;19(3):210-216. DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; POEM, Patient-Oriented Eczema Measure; SCORAD, Scoring Atopic Dermatitis It is critical to fully understand the impact of AD from the patient’s perspective

Assessing the Burden of Atopic Dermatitis in Clinical Practice AAD guidelines recommend that clinicians ask general questions about itch, sleep, impact on daily activity, and disease persistence How long have you had your AD?Is your AD active in bursts or tends to be active all the time?Could you tell me how AD has affected you emotionally? Could you tell me how AD has affected your sleep?Could you tell me how AD has affected you at school or work? Could you tell me how AD has affected your social life? What are your goals for treatment of AD? Could you tell me about the side effects that you have experienced from treatment for your AD, or that you are concerned about? Eichenfield LF, et al. J Am Acad Dermatol.  2014;70(2):338-351.AAD, American Academy of Dermatology

Associated Comorbidities Other atopic diseases NeuropsychiatricCardiovascular diseasesOthersOsteoporosisInjuriesDevelopmental issuesInfectionsSilverberg JI. Clin Dermatol. 2017;35:360-366.

Association of Pediatric and Adult Atopic Dermatitis with Comorbid Atopic Disease Silverberg JI, et al. Pediatr Allergy Immunol. 2013;24(5):476-486. National Health Interview Survey 2012 (n=34,500 adults ages 18-85 years). National Survey of Children’s Health 2007-2008 (n=91,642 children). Percent of Persons Percent of Persons

Atopic Dermatitis and Mental Health Group Odds Ratio 95% CI Adults/Children with vs without AD 1.71 1.48-1.98Adults with vs without AD2.081.70-2.55Children with vs without AD 1.310.99-1.75Adults/Children with moderate-severe AD vs without AD1.811.40-2.35Adults/Children with mild AD vs without AD1.280.41-4.06CI, confidence intervalPatel KR, et al. J Am Acad Dermatol. 2019;80(2):402-410. Depression is more common in persons with vs without ADSuicidal ideation is more common in persons with vs without ADGroupOdds Ratio95% CIAdults/Children with vs without AD1.971.19-3.25 Adults with vs without AD2.871.89-4.36

Atopic Dermatitis and Cardiovascular Comorbidities Kantor R, et al. J Am Acad Dermatol . 2016;75(6):1119-1125. Silverberg JI, et al. J Investig Dermatol . 2016;136(8):1714-1716. Silverberg JI. J Allergy Clin Immunol . 2016;137(3):938-940. Silverberg JI. J Allergy Clin Immunol. 2015;136(3):824-825. Silverberg JI, et al. J Allergy Clin Immunol. 2015; 135(3): 721-728. Silverberg JI, et al. JAMA Dermatol. 2015 1;151(2):144-152. Andersen YM, et al. J Allergy Clin Immunol. 2016;138(1):310-312. Su VY, et al. Ann Med. 2014;46(2):84-89.CADAnginaMIStrokePVDHypertensionDyslipidemiaPrediabetesT2 Diabetes

Atopic Dermatitis and Osteoporosis/Osteopenia Analysis of 2006-2012 NEDS2002-2012 NISTotal number of encounters (age ≥50 y)NEDS: 61,065,660NIS: 44,425,777 NEDS, National Emergency Department Sample; NIS, Nationwide Inpatient Sample Shaheen MS, et al. J Am Acad Dermatol . 2019;80(2):550-551.

Atopic Dermatitis and Risk of Infection Infection Odds Ratio 95% Confidence IntervalEar infection 1.29 1.16-1.43 Strep throat2.311.66-3.22Urinary tract infection 2.311.66-3.22Pneumonia1.720.75-3.98Serrano L, et al. J Am Acad Dermatol. 2018;doi: 10.1016/j.jaad.2018.11.028.

Risk Factors Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.Kelleher et al. J Allergy Clin Immunol . 2015;135:930-935.

Atopic Dermatitis Is a Complicated Disease https://en.wikipedia.org/wiki/Spongiosis. http://creativecommons.org/licenses/by-sa/3.0/

Key Cytokine Targets in Atopic Dermatitis Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50.

Immunologic Pathways Vakharia PP, et al. BioDrugs. 2017;31:409-422.

Immunologic Targets in Atopic Dermatitis: Th2 Pathway Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50.

Selected Treatment Targets Gandhi NA, et al. Nat Rev Drug Discov . 2016;15(1):35-50.

Goals of Therapy Reduce the number and severity of flares Reduce pruritus and improve quality of lifeMaintain normal activities of daily livingMaximize disease-free periods Prevent infectious complicationsAvoid/Minimize side effects of treatment Schneider L, et al. J Allergy Clin Immunol . 2013;131(2):295-299.Lyons JJ, et al. Immunol Allergy Clin North Am. 2015;35(1):161-183.

Key Recommendations for Basic Management Recommendation Strength Level  Moisturizers should be an integral part of treatment since there is strong evidence that their use can reduce disease severity and the need for pharmacologic interventionA IBathing is suggested as part of treatment and maintenance; however, there is no standard for the frequency or duration of bathingCIII Moisturizers should be applied soon after bathing to improve skin hydrationBIILimited use of nonsoap cleansers (that are neutral to low pH, hypoallergenic, and fragrance free)CIIIThe addition of oils, emollients, and most other additives to bath water and the use of acidic spring water cannot be recommendedCIIIEichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.

“A” Rated Evidenced-Based Approaches For use of moisturizers For use of topical corticosteroids Consider steroid side effectsFor use of topical calcineurin inhibitors Use for steroid sparing Use off label in children <2 yearsUse for proactive maintenanceAgainst routine use of topical antistaphylococcal treatments Eichenfield L, et al. J Am Acad Dermatol. 2014;71:116-132.

Skin Hydration Bathing followed by immediate application of emollient EmollientUse generously - no danger from “excess use”Lotions vs creams vs oils vs ointmentsGeneral recommendations are:Warm (not hot) waterBath better than shower5-10 minutesNeutral/low pH, hypoallergenic, fragrance-free non-soap cleansers preferredBleach baths now standard of maintenance care for pediatric moderate-to-severe ADSchneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.

Trigger Avoidance Identify and eliminate triggering factors Avoidance of common irritants – soaps/detergents/wool/occlusive fabricsPotential contact allergens, such as fragrance, preservatives, botanicalsRecommend control of temperature and humidityConsider possible allergy triggers (other than foods) with skin tests, although skin tests (and allergy patch tests) are poorly predictive of triggering factorsAllergen immunotherapySelected patients with aeroallergen sensitivity – may worsen ADLimited data regarding the benefits of leukotriene inhibitors (shown to be ineffective for AD) Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Patient Education Regarding Disease State Patient and family education Chronic nature of disease, exacerbating factors, efficacy and safety of treatmentsDemonstrate skin care techniquesProvide written treatment planRefer to other health care providers as neededAdvise of patient support organizationsPatient and family quality of life often impairedAdditional treatment may be needed for itching, behavioral disorders, mental health disorders, and sleep disturbances Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Treatment Overview Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.

Patient Adherence to Atopic Dermatitis Treatment Is Poor Krejci-Manwaring J, et al. J Am Acad Dermatol. 2007;56(2):211-216.

Why Are Patients Non-Adherent? Poor motivation The patient may not be particularly bothered Secondary gain Seeking disability or other gain Lack of trust in doctor Physician-patient relationship is the foundation Fear of medication Founded or unfounded fear of treatment Don’t know what to do Patients may not remember oral instructions Burden of treatmentSometimes the treatment is worse than the disease! Perceived burdenSometimes treatment seems worse than the disease Passing the responsibility buckWith multiple caregivers, no one may take responsibility Forgetfulness“Pavlov’s dog” problem LazinessNo energy to follow treatment ResignationSome patients have just given up

Advanced : Psychological Techniques 1. Employing anchoring techniques 2. Recognizing probability bias 3. Providing salient descriptions 4. Understanding loss aversion 5. Framing risks of adverse effects 6. Using adverse effects to advantage 7. Rewarding and praising children Basics : Complexity, Cost, and Instructions 1. Reduce treatment burden 2. Written instructions 3. Triggers 4. Steroid phobia Foundation : Trust and Accountability1. The physician-patient relationship 2. Follow-upAdherence Intervention PyramidLewis DJ, Feldman SR. Practical Ways to Improve Patient Adherence, 2017.

Reminders Are Not The Same As Accountability Yentzer B, et al. J Am Acad Dermatol . 2011;64:793-795.

Specific Strategies to Promote Adherence Build trust Simplify treatmentUse combination products when appropriate“This is the treatment that most children/teenagers use for this condition”Prescribe only “all natural” treatments Provide a written action planProvide your cell phone number Frequent follow-up visits, particularly after treatment is initiated or changed Provide positive reinforcement Ask what difficulty they may be having with treatment

Case Scenario #2 Anita is a 6-year-old female diagnosed at age 11 months with AD primarily involving her forearms and lower legs Current treatmentDaily bathing followed by emollients 1-2 x/dayDilute bleach bath once or twice weeklyUpon questioning, Anita reports that her pruritus has not improved, and is sometimes unbearable when she plays outdoors. She also says it is sometimes difficult to fall asleepPE: moderate erythema with numerous excoriations noted on neck, arms, and legs; no sign of infection

Topical Corticosteroids Use when nonpharmacologic interventions have failed Effective for both active inflammation and disease prophylaxisAcute treatment of active inflammation: intermediate-/high-potencyProphylaxis: low-potencyFrequencyAcute inflammation: twice-daily application generally usedProactive maintenance: once- or twice-weekly to commonly flaring areasEichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Topical Corticosteroids (cont) Quantity- fingertip unit per area equivalent to 2 palms Caution- areas of thin skinAdverse effectsLocal: acneiform or rosacea-like eruptions, focal hypertrichosis, purpura, atrophy, striae, telangiectasiaSystemic- rareEichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Topical Calcineurin Inhibitors Non-steroidal therapy for acute flares and maintenance therapy in adults and children age >2 y May use in combination with topical corticosteroid initially for acute inflammationSteroid-sparing option for sensitive or thin skinEichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Topical Calcineurin Inhibitors (cont) Frequency Acute inflammation- twice-daily applicationProactive maintenance- twice-/thrice-weeklyAdverse effectsLocal: burning, stinging, pruritusSystemic- rare; no need for routine blood monitoringPatient education about boxed warning Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Crisaborole: Results of 2 Phase 3 Studies Paller AS, et al. J Am Acad Dermatol . 2016;75(3):494-503. P =.038 P<.001P<.001 P<.001P<.001P<.001P=.008AD-301: Crisaborole (n=503), vehicle (n=256); AD-302: crisaborole (n=513), vehicle (n=250)

Crisaborole Safety Adverse Event* Crisaborole (n=1012)Vehicle(n=499) P Treatment-related burning and stinging 4.4%1.2%0.001Infections and infestations 11.711.8–Gastrointestinal disorders2.72.4–Respiratory, thoracic, and mediastinal disorders4.63.0–Application site pain 4.41.20.001Skin and subcutaneous tissue disorders3.74.2–Nervous system disorders1.40.4– Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503.*Treatment-emergent adverse evens (≥1% of patients)

Wet Wrap Therapy Concomitant use with topical corticosteroid (but not topical calcineurin inhibitor) for recalcitrant atopic dermatitis Caution about overuse due to folliculitis, skin maceration, secondary infections Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Others Possibly effective (?) Bleach bath1Appears to be no more effective than water in reducing AD severity2Proactive use for patients with recurrent skin infections However, concern of widespread antimicrobial resistanceConcomitant use of intranasal mupirocinNot recommended Topical antihistamines Not recommended due to risk of absorption and development of photoallergic contact dermatitis 11. Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.2. Chopra R, et al. Ann Allergy Asthma Immunol . 2017;119;435-440.

Optimization of Topical Care: My Anecdotal Experience Topical treatments can be extraordinarily effective Adherence is crucialKeep treatment as simple as possibleHigher potency steroid given less frequently may be appropriateReinforce best practices at each visit

Case Scenario #3 Phil is a 20-year-old male with a 4-year history of atopic dermatitis. He is being referred by his primary care physician for worsening symptoms. Although he has done his best to identify and minimize triggers, his atopic dermatitis has worsened since he began attending college and living in a dormitoryHe is diagnosed with moderate atopic dermatitisIGA 3 with 12% of his body surface area affectedCurrent treatment:Daily bathingTwice-daily moisturizerTwice-daily crisaborole

Selected Treatment Targets Gandhi NA, et al. Nat Rev Drug Discov . 2016;15(1):35-50.Stop 7.2

Systemic Immunosuppressants Recommended for severe atopic dermatitis refractory to topical regimens and phototherapy or when QOL is severely affected Cyclosporine, methotrexate, mycophenolate mofetil, azathioprine more effective than interferon- and oral calcineurin inhibitorsNo specific recommendations regarding optimal dosing and duration Adverse effects- close monitoring is recommendedEichenfield LF, et al. J Allergy Clin Immunol . 2017;139:S49-S57.

Systemic Corticosteroids Avoid if possible, particularly in children Short-term use of acute inflammationPossible role as bridge therapy to another systemic, steroid-sparing treatmentEichenfield LF, et al. J Allergy Clin Immunol . 2017;139:S49-S57.

Dupilumab*: Phase 3 Trials (SOLO 1 and SOLO 2) * Approved dose is an initial dose of 600 mg followed by 300 mg every other week †Reduction from baseline of ≥2 points on the IGA at week 16.§Improvement from baseline of at least 75% on the Eczema Area and Severity Index (EASI) at week 16. P <.001 for all comparisons between dupilumab and placebo Simpson EL, et al. N Engl J Med. 2016;375(24):2335-2348.

Dupilumab: Phase 3 Trials (SOLO 1 and SOLO 2) (cont) Significantly greater improvement with dupilumab vs placebo regarding PruritusSleepSymptoms of anxiety or depressionQuality of lifeFewer patients treated with dupilumab used rescue medication19% vs 52%Simpson EL, et al. N Engl J Med. 2016;375(24):2335-2348.

Dupilumab*: Phase 3 Trials (SOLO 1 and SOLO 2) (cont) Adverse Event, % SOLO1 SOLO 2 Placebo (n=222) Dupilumab QOW(n=229) Dupilumab QW(n=218)Placebo(n=234)Dupilumab QOW(n=236)Dupilumab QW(n=237)≥1 AE657369726566≥1 Serious AE531623 Injection site reaction681961413AD exacerbation301310351416Headache695 589Allergic conjunctivitis153111Conjunctivitis153<144Nasopharyngitis810119 88Non-skin infection223031242526Simpson EL, et al. N Engl J Med. 2016;375(24):2335-2348.*Approved dose is an initial dose of 600 mg followed by 300 mg every other week

Phototherapy Recommended for atopic dermatitis refractory to topical treatments Specific situationsUVA1- acute exacerbationsUVB- chronic atopic dermatitisUVA with psoralen- severe widespread atopic dermatitisAdverse effects Local: actinic damage, local erythema and tenderness, altered pigmentationSystemic: infrequentEichenfield LF, et al. J Allergy Clin Immunol . 2017;139:S49-S57.

Other Systemic Therapies Antihistamines- consider short-term use of sedating antihistamine for short-term use for sleep disturbance due to pruritus AntimicrobialsNot routinely recommendedConsider if evidence of bacterial infection, eczema herpeticumVitamin D- consider if low level or poor intakeOthers- limited/no evidence Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Selected Treatment Targets Gandhi NA, et al. Nat Rev Drug Discov . 2016;15(1):35-50.

Selected Phase 2/3 Investigational Agents Class/Target(s) Agent(s) Janus kinase inhibitors Baricitinib Tofacitinib Upadacitinib PF-04965842Delgocitinibwww.ClinicalTrials.gov Agents shown in red have published results of a phase 2/3 clinical trial for atopic dermatitis

Selected Phase 2/3 Investigational Agents (cont) Class/Target(s) Agent(s) Janus kinase inhibitors Baricitinib Tofacitinib Upadacitinib PF-04965842DelgocitinibAnti-IL-13 mAbLebrikizumabTralokinumabAnti-IL-17 mAbSecukinumab www.ClinicalTrials.gov Agents shown in red have published results of a phase 2/3 clinical trial for atopic dermatitis

Selected Phase 2/3 Investigational Agents (cont) Class/Target(s) Agent(s) Janus kinase inhibitors Baricitinib Tofacitinib Upadacitinib PF-04965842DelgocitinibAnti-IL-13 mAbLebrikizumabTralokinumabAnti-IL-17 mAbSecukinumabAnti-IL-22 mAb FezakinumabAnti-IL-31RA mAbNemolizumabwww.ClinicalTrials.gov Agents shown in red have published results of a phase 2/3 clinical trial for atopic dermatitis

Selected Phase 2/3 Investigational Agents (cont) Class/Target(s) Agent(s) Janus kinase inhibitors Baricitinib Tofacitinib Upadacitinib PF-04965842DelgocitinibAnti-IL-13 mAbLebrikizumabTralokinumabAnti-IL-17 mAbSecukinumabAnti-IL-22 mAb FezakinumabAnti-IL-31RA mAbNemolizumabNK-1 receptor antagonistTradipitantAnti-IgELigelizumabOmalizumabMED14212 www.ClinicalTrials.gov Agents shown in red have published results of a phase 2/3 clinical trial for atopic dermatitis

Baricitinib Phase 2, randomized, double-blind, placebo-controlled trial N=124 patients with moderate/severe ADRun-in phase with topical corticosteroids x 4 weeksRandomized to 16 weeks of treatment with:Baricitinib 2 mg once daily Baricitinib 4 mg once dailyPlacebo once dailyResults EASI-50: baricitinib 4 mg (61%) vs placebo (37%) Significant difference seen at week 4 Pruritus and sleep loss also improved with baricitinibTreatment-emergent adverse eventBaricitinib 2 mg (46%)Baricitinib 4 mg (71%)Placebo (49%) Guttman-Yassky E, et al. J Am Acad Dermatol. 2018;doi:10.1016/jaad.2018.01.018.

Tofacitinib Phase 2a randomized, double-blind, vehicle-controlled study N=69 adults with mild/moderate ADRandomized to 4 weeks of treatment withTofacitinib 2% twice dailyVehicle twice dailyTreatment-emergent AE: tofacitinib (31%); vehicle (56%) Bissonnette R, et al. Br J Dermatol. 2016;175:902-911. Mean Percentage Change in EASI Total Score Proportion Achieving PGA of 0/1 plus ≥2-point Improvement from Baseline * P<0.05; **P<0.001; ***P<0.0001

Upadacitinib Phase 2b randomized, double-blind, placebo-controlled study N=67 adults with moderate/severe ADRandomized (1:1:1:1) to 16 weeks of treatment withUpadacitinib 7.5 mg, 15 mg, or 30 mg once dailyPlaceboAt week 16Patients treated with upadacitinib were rerandomized to continue upadacitinib or switched to placebo once dailyPatients treated with placebo were rerandomized to continue placebo or switched to upadacitinib 30 mg once daily At week 20, rescue upadacitinib 30 mg once daily provided at first instance of EASI 50https://www.prnewswire.com/news-releases/abbvie-presents-upadacitinib-longer-term-32-week-and-patient-reported-outcomes-data-from-phase-2b-atopic-dermatitis-study-at-27th-european-academy-of-dermatology-and-venereology-eadv-congress-300711938.html EASI, Eczema Area and Severity Index

Upadacitinib (cont) EASI, Eczema Area and Severity Index Itch was rated from 0 (no itch) to 10 (worst imaginable) https://www.prnewswire.com/news-releases/ abbvie-presents-upadacitinib-longer-term-32-week-and-patient-reported-outcomes-data-from-phase-2b-atopic-dermatitis-study-at-27th-european-academy-of-dermatology-and-venereology-eadv-congress-300711938 .html ● EASI 90 at 16 weeks was achieved by 10%, 14%, 26%, and 50% (placebo; upadacitinib 7.5 mg, 15 mg, 30 mg, respectively)● Improvement in patient-reported outcomes (pain, sleep)● 2 serious adverse events (infection, non-melanoma skin cancer) in placebo/upadacitinib 30 mg group

PF-04965842 AE, adverse event; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT02780167?term=pf-04965842&cond=Atopic+Dermatitis&rank=1 Phase 2 randomized, double-blind, placebo-controlled study N=269 adults with moderate/severe AD Randomized to 12 weeks of treatment with: PF-04965842 10 mg, 30 mg, 100 mg, or 200 mg QDPlacebo QDViral upper respiratory tract infection most common AE: PF-04965842 (10.2-17.9%); placebo (8.9%)

Nemolizumab: XCIMA Trial Phase 2, randomized, double-blind, placebo-controlled trial N=264 patients with moderate/severe AD inadequately controlled with topical treatmentRandomized to 12 weeks of treatment with:Nemolizumab 0.1 mg/kg Q4 wksNemolizumab 0.5 mg/kg Q4 wksNemolizumab 2 mg/kg Q4 wksPlacebo Q4 wksNemolizumab 2 mg/kg Q8 wks Nasopharyngitis most common AE: nemolizumab (10-17%); placebo (15%)Ruzicka T, et al. N Engl J Med. 2017;376(9):826-835. Change from Baseline in Pruritus Score at Week 12 AE, adverse event

Omalizumab A meta-analysis and systematic review found no concrete evidence demonstrating effectiveness of omalizumab for AD 1 Severe adverse effects may limit its use in AD2 Anaphylaxis, cardiovascular, and cerebrovascular eventsIt remains to be determined if omalizumab is effective in subgroups of patients with AD1 1. Wang HH, et al. J Allergy Clin Immunol. 2016;138:1719-1722.2. Wang D, et al. Am J Clin Dermatol. 2016;17:425-443.