I N T R O D U C T I O N • �Atopic�dermatitis�(AD)�is�a�relapsing,�chronic,�pruritic,�inflammatory�skin�disease� associated�with�gene-environment�interactions,�immune�dysregulation,�and�skin� barrier�dysfunction.1 � –��AD�affects�around�3.2%�of�adults�in�the�USA.2 • �Severe�disease�is�often�associated�with�significant�disability,�leading�to�high� socioeconomic�costs�including:�psychological�problems,�significant�sleep�loss,� and�impaired�quality�of�life.3 • �The�current�treatment�approach�for�AD�is�to�reactively�treat�flares. � –��Topical�corticosteroids�are�most�frequently�prescribed�for�the�treatment�of�AD;4 however, in patients with moderate-to-severe disease and inadequate response�to�topical�therapy,�more�aggressive�systemic�therapies�are� medically�necessary.5 • �At�present,�the�real-world�treatment�patterns�and�unmet�needs�of�adult�patients� with�moderate-to-severe�AD�are�poorly�quantified�for�patients�treated�with� systemic�therapies. O B J E C T I V E • �To�evaluate�from�a�patient�perspective�the�adequacy�of�systemic�treatment�and� to�document�potential�unmet�needs�in�the�treatment�of�moderate-to-severe�AD.� M E T H O D S • �The�study�was�a�longitudinal�prospective�observational�study�of�adult�patients� with�moderate-to-severe�AD,�receiving�a�systemic�medication�for�the�treatment�of� AD�in�the�previous�6�months. • �Study�subjects�were�adult�commercial�health�plan�enrollees�with�AD,�identified� from�the�Optum�Research�Database. • �AD�was�defined�using�International�Classification�of�Disease,�Ninth�or�Tenth� Revision,�Clinical�Modification�(ICD-9-CM�or�ICD-10-CM). • �Eligible�study�participants�were�invited�by�mail�to�participate�in�a�baseline�paper� survey,�followed�by�web-based�surveys�at�3,�6,�9,�and�12�months.�Monthly� abbreviated�web-based�surveys�were�also�included. • �Diagnosis�of�AD,�moderate-to-severe�AD�(during�the�previous�12�months),�and� systemic�medication�use�was�verified�by�patients�at�the�time�they�completed�the� baseline�survey. • �An�informed�consent�statement�was�provided�with�the�paper�survey,�and�consent� for�study�participation�was�implied�when�the�survey�was�returned. Inclusion criteria • �Aged�≥18�years. • �At�least�one�medical�claim�with�an�ICD-9-CM�diagnosis�code�for�AD�(691.8)�or� ICD-10-CM�diagnosis�code�(L200,�L2081,�L2082,�L2083,�L2084,�L2089,�L209)� from�a�dermatologist�or�allergist/immunologist�over�the�last�5�years;�or • �At�least�one�medical�claim�with�a�diagnosis�code�for�contact�dermatitis�due�to�an� unspecified�condition�(ICD-9:�692.9,�ICD-10:�L259)�or�rash�and�other� non-specific�skin�eruption�(ICD-9:�782.1,�ICD-10:�R21)�from�a�dermatologist�or� allergist/immunologist�over�the�last�5�years;�and at least two non-diagnostic medical�claims�at�least�30�days�apart�with�a�diagnosis�code�for�asthma,�food� allergies,�or�allergic�rhinitis. • �At�least�one�pharmacy�claim�or�medical�claim�over�the�last�6�months�for:�at�least� one�oral�corticosteroid;�at�least�one�injectable�corticosteroid;�at�least�one� phototherapy�treatment;�or�any�immunosuppressant. • �Continuous�enrollment�with�both�medical�and�pharmacy�benefits�in�a�large� commercial�US�health�plan�affiliated�with�Optum�during�the�past�6�months.� • �Able�and�willing�to�complete�surveys. • �Self-reported�AD�diagnosis�in�the�patient�survey.� • �Moderate-to-severe�AD�over�the�past�12�months�using�the�Rajka�and� Langeland�criteria.6 Exclusion criteria • �Participation�in�a�clinical�trial�for�AD�in�the�last�6�months. • �At�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with�a� diagnosis�code�for�conditions�that�may�be�treated�with�systemic�steroids�during� the�last�5�years. • �At�least�one�pharmacy�or�medical�claim�for�an�immunosuppressant�in�the�last� 5�years�and�at�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with� a�diagnosis�code�for�conditions�that�may�be�treated�with�immunosuppressants. • �At�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with�a� diagnosis�code�that�may�be�treated�with�systemic�immunosuppressants�within� the�past�5�years. • �At�least�two�non-diagnostic�claims�at�least�30�days�apart�with�a�code�indicating�a� solid�organ�transplant�over�the�last�5�years. • �Surveys�that�were�partially�completed,�ineligible,�returned�too�late,�or�had� non-responses�were�excluded. Survey outcomes • �The�baseline�paper�survey�collected�the�following�from�patients: � –��Sociodemographic�characteristics:�race,�ethnicity,�marital�status,�education� level,�and�household�income�level. � –��Medical�history:�patient�confirmation�of�AD�diagnosis�by�a�healthcare� professional,�age�at�AD�diagnosis,�and�self-reported�disease�severity�using�the� Rajka�and�Langeland�criteria.6 � –��Signs�and�symptoms�of�AD:�patient-reported�flares,�Patient-Orientated�Eczema� Measure�(POEM)7�and�the�pruritus�Numeric�Rating�Scale�(NRS).8 � –��Disease-specific�quality�of�life�assessed�using�the�Dermatology�Life�Quality� Index�(DLQI)9�and�work�productivity�assessed�by�the�Work�Productivity�and� Activity�Impairment�Scale�(WPAI).10 � –��Prior�and�ongoing�medications�for�AD:�systemic�immunosuppressants�and� corticosteroids,�topical�corticosteroids�and�immunomodulators,�phototherapy,� antibiotics,�and�antihistamines. � –��Treatment�satisfaction�using�the�Treatment�Satisfaction�Questionnaire�for� Medication�(TSQM-II).11 Statistical analysis • �Chi-square�tests�and�t-tests�were�used�for�bivariate�comparisons�of�demographics� and�outcome�measures�based�on�the�distribution�of�the�measure.�Spearman’s� rank-order�correlation�analyses�were�conducted�to�examine�the�relationship� between�number�of�flares�and�select�patient-reported�outcome�measures. –��Unless�otherwise�specified,�tests�of�significance�were�two-tailed�and�carried� out�at�the�5%�level�of�significance.� R E S U LT S Demographics, AD history and medication use • �From�6000�potential�study�participants,�5199�patients�were�excluded�and�801� (13.4%)�were�included�in�the�analysis. � –��Mean�age�of�patients�was�45.2�years;�71.8%�were�female;�83.7%�were� Caucasian�(Table 1).� • �Many�patients�(66.3%)�reported�that�they�were�diagnosed�with�AD�after�the�age� of�20. � –��Per�the�self-completed�Rajka�and�Langeland�criteria,�73.7%�of�patients�had� moderate�AD�and�26.3%�had�severe�AD. –���In�the�12�months�prior�to�baseline,�38.3%�of�patients�reported�no�remission,� 35.8%�reported�<3�months�of�remission,�and�25.8%�reported�3�or�more�months� of�remission�(Table�1). • �Medication�used�within�the�last�month�included:�topical�corticosteroids,�63.6%;� topical�calcineurin�inhibitors,�7.7%;�oral�corticosteroids,�8.5%;�and oral immunosuppressants,�5.0%�(Figure 1). A Real-World Study Evaluating AdeQUacy of Existing Systemic Treatments for Patients with Moderate-to-Severe Atopic Dermatitis (AD-QUEST): Baseline Treatment Patterns and Unmet Needs Assessment Wenhui Wei1*, Eric Ghorayeb2, Michael Andria3, Valery Walker4, Jingdong Chao3, James Schnitzer2, Martha Kennedy3, Zhen Chen3, Angela Belland4, John White4, Jonathan I. Silverberg5 1Formerly of Sanofi, Bridgewater, NJ, USA; 2Sanofi Bridgewater, NJ, USA; 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 4Optum, Eden Prairie, MN, USA; 5Northwestern University Feinberg School of Medicine, Chicago, IL, USA *Current address: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Presented at the Annual Winter Clinical Dermatology Conference Hawaii, January 12–17, 2018, Maui, Hawaii Previously presented at the 76th Annual Meeting of the Society for Investigative Dermatology (SID), April 26–29, 2017, Portland, Oregon Table 1. Baseline demographic characteristics and AD diagnosis and severity. Characteristics Total (N = 801) Age�(years),�mean�(SD) 45.21�(13.84) n % Age group 18–44 363 45.32 45–64 396 49.44 65+ 42 5.24 Gender Male 226 28.21 Female 575 71.79 Geographic region Northeast 72 8.99 Midwest 185 23.10 South 402 50.19 West 142 17.73 Hispanic Yes 67 8.48 No 723 91.52 Race* White�or�Caucasian 665 83.65 Black�or�African�American 66 8.30 American�Indian�or�Alaska�Native 15 1.89 Asian�or�Pacific�Islander 41 5.16 Other 31 3.90 Missing 6 – Employed† Yes 631 78.78 No 170 21.22 Age at AD diagnosis Under�5�years 99 12.41 5–10�years 59 7.39 11–20�years� 111 13.91 21�years�or�older 529 66.29 Missing 3 – AD�severity�categories�(Rajka�and�Langeland�grading�system) Moderate�(4.5–7.5) 590 73.66 Severe�(8–9) 211 26.34 AD�severity�score�(Rajka�and�Langeland�grading�system),�mean�(SD) 6.67�(1.21) Total�time�patients�experienced�remission�from�AD No�remission�during�last�12�months 307 38.33 <3�months�of�remission�during�the�last�12�months 287 35.83 3�or�more�months�of�remission�during�the�last�12�months 207 25.84 SD,�standard�deviation.�*Respondent�could�select�more�than�one�response;�†Employment�status�(working�for�pay)�was�derived�from�the� first�question�in�the�WPAI Table 2. Baseline AD flares. AD flares Total (N = 801) n % Are�you�currently�experiencing�a�flare�of�your�AD? Yes 449 56.20 No 350 43.80 Missing 2 – Over�the�past�month,�how�many�flares�have�you�experienced? 0 149 18.70 1 186 23.34 2 157 19.70 >2 305 38.27 Missing 4 – Over�the�past�month,�on�average,�approximately�how�long�did�each�flare(s)�last? <1�week 145 22.34 1�week�to�<2�weeks 205 31.59 2�weeks�to�<3�weeks 117 18.03 3�or�more�weeks 182 28.04 Have�you�recovered�from�your�most�recent�flare? I�have�completely�recovered 84 12.96 I�have�partially�recovered 422 65.12 I�have�not�recovered�at�all 142 21.91 Over�the�past�month,�how�often�did�you�worry�about�having�a�flare�of�your�AD Always 170 21.30 Often 188 23.56 Sometimes 237 29.70 Rarely 136 17.04 Never 67 8.40 Missing 3 – Over�the�past�month,�on�average,�how�worried�were�you�about�your�next�flare? Extremely�worried 74 9.28 Very�worried 115 14.43 Somewhat�worried 283 35.51 Not�very�worried 228 28.61 Not�at�all�worried 97 12.17 Missing 4 – Table 3. Baseline AD patient-reported outcomes. Total (N = 801) n Mean (SD) DLQI score* 789 6.44�(6.28) n % DLQI categories No�effect�on�QoL 180 22.81 Small�effect�on�QoL 263 33.33 Moderate�effect�on�QoL 176 22.31 Very�large�effect�on�QoL 131 16.60 Extremely�large�effect�on�QoL 39 4.94 Missing 12 – n Mean (SD) TSQM score† Effectiveness 800 50.08�(24.20) Side�effects 799 87.85�(23.31) Convenience 796 64.09�(17.53) Global�satisfaction 797 60.17�(21.47) WPAI score‡ Absenteeism�(hours�missed�from�work�in�the�past� 7�days�due�to�AD) 625 0.63�(3.16) Number�of�hours�missed�for�those�who�missed� >0�hours�(due�to�AD) 56 7.05�(8.19) Percent�impairment�while�working�in�the�past� 7�days�due�to�AD 559 14.74�(21.35) Presenteeism (unproductive hours in the past 7�days�due�to�AD) 559 5.53�(8.37) Work�productivity�loss�(in�hours)�in�past�7�days� (absenteeism + presenteeism) due to AD 558 6.11�(9.43) Percent�impairment�in�regular�daily�activities�in� the�past�7�days�due�to�AD 792 18.88�(24.76) n % Work�time�missed�due�to�AD 564 2.11 *DLQI�scores�range�from�0�(no�effect�on�QoL)�to�30�(extremely�large�effect�on�QoL).�†TSQM�scores�range�from�0–100�where�higher� scores�represent�better�satisfaction.� ‡Higher�WPAI�scores�indicate�greater�impairment. Acknowledgements The�study�was�funded�by�Sanofi�and�Regeneron�Pharmaceuticals�Inc.�Medical�writing�support�was�provided�by�Abby�Armitt,�Prime,� Knutsford,�UK�and�funded�by�Sanofi�and�Regeneron�Pharmaceuticals,�Inc. Disclosures Wenhui�Wei�is�a�former�employee�and�current�stockholder�of�Sanofi�and�an�employee�of�Regeneron�Pharmaceuticals,�Inc.�Eric�Ghorayeb� and�James�Schnitzer�are�employees�of�and�stockholders�in�Sanofi.�Michael�Andria,�Jingdong�Chao,�Martha�Kennedy�and�Zhen�Chen�are� employees�of�and�stockholders�in�Regeneron�Pharmaceuticals,�Inc.�Valery�Walker,�Angela�Belland�and�John�White�are�employees�of� Optum,�a�company�that�received�research�funding�for�the�current�study.�Jonathan�Silverberg�is�a�member�of�an�institution�that�received� research�funding�for�the�current�study. C O N C L U S I O N S • �Despite�standard-of-care�treatments,�adults�with�moderate-to-severe�AD�report� high�disease�burden�from�disease�symptoms,�recurrent�flares�and�impaired�QoL,� suggesting�significant�unmet�therapeutic�needs. No oral immunosuppressants or corticosteroids No injectable immunosuppressants or corticosteroids No oral or injectable immunosuppressants or steroids Injectable immunosuppressants (methotrexate) Oral or injectable methotrexate Oral corticosteroids Any systemic steroids* Injectable corticosteroid Any systemic immunosuppressant* Oral immunosuppressant Topical corticosteroids Topical calcineurin inhibitors Phototherapy Antibiotics Any antihistamine Antihistamines with a prescription Antihistamines without a prescription 0 10040302010 60 87.56 95.00 85.16 0.62 1.12 8.49 11.36 4.37 5.12 4.99 63.55 7.74 2.12 4.74 38.20 13.11 32.83O th er m ed ic at io ns fo r A D S ys te m ic m ed ic at io ns fo r A D 7050 80 90Within the last month (n = 801) Percentage Figure 1. Baseline AD medication used within the last month. *Oral�or�injectable Side effects Convenience Global satisfaction 0 5040302010 60 P < 0.0001 P < 0.0001 P < 0.0001 P < 0.0001Effectiveness 58.10 (SD 23.19) 43.86 (SD 23.17) 50.10 (SD 24.22) 91.63 (SD 19.04) 84.86 (SD 25.83) 87.82 (SD 23.33) 61.06 (SD 17.29) 64.14 (SD 17.52) 68.08 (SD 17.04) 66.91 (SD 19.34) 54.95 (SD 21.53) 60.20 (SD 21.42) 908070 100 Total Currently experiencing a flare Not currently experiencing a flare Mean TSQM score Absenteeism (hours missed from work) Number of hours missed for those who missed >0 hours Percent impairment while working Presenteeism (unproductive hours) Work hours lost (in hours) Percent impairment in regular daily activities 0 252015105 30 P = 0.071 P = 0.446 P < 0.0001 P < 0.0001 P < 0.0001 P < 0.0001 0.63 (SD 3.16) 0.83 (SD 3.41) 0.38 (SD 2.80) 7.05 (SD 8.19) 6.61 (SD 7.44) 8.67 (SD 10.73) 14.76 (SD 21.38) 20.00 (SD 24.27) 7.78 (SD 14.04) 5.54 (SD 8.38) 7.35 (SD 9.53) 3.12 (SD 5.73) 6.11 (SD 9.44) 8.17 (SD 10.71) 3.39 (SD 6.51) 18.90 (SD 24.79) 25.88 (SD 27.55) 10.03 (SD 17.07) Total Currently experiencing a flare Not currently experiencing a flare Mean *TSQM�scores�range�from�0–100�where�higher�scores�represent�better�satisfaction.�†Higher�WPAI�scores�indicate�greater�impairment� and�are�for�over�the�past�7�days�due�to�AD. Figure 3. Baseline AD patient-reported outcomes by current AD flare status A) Mean TSQM score*; B) Mean WPAI score†. A) B) L I M I TAT I O N S • �This�study�was�a�patient�survey�where�recall�bias�was�a�limitation. • �Additionally,�in�the�current�baseline�analysis,�patients’�assessment�of�outcomes� like�DLQI�were�based�on�the�past�7�days�and�may�not�capture�the� comprehensive�impact�of�change�to�AD,�given�the�fluctuation�of�the�disease. • �Since�AD-QUEST�was�a�longitudinal�survey,�the�follow-up�survey�should�provide� more comprehensive understanding�of�the�disease�burden. 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 n = 799 n = 449 n = 350 10.29 (SD 7.62) 13.50 (SD 6.94) 6.17 (SD 6.38) P O E M s co re * Total Currently experiencing a flare Not currently experiencing a flare 10 9 8 7 6 5 4 3 2 1 0 P ru ri tu s N R S s co re † n = 795 n = 447 n = 348 n = 794 n = 446 n = 348 5.11 (SD 3.22) 6.34 (SD 2.58) 3.52 (SD 3.27) 3.70 (SD 2.78) 4.82 (SD 2.56) 2.26 (SD 2.34) Itch at worst moment during 24 hours Itch overall (on average) during 24 hours Figure 2. Baseline AD patient-reported outcomes by current AD flare status: A) POEM score; B) Pruritus NRS score. *POEM�scores�range�from�0�(no�eczema)�to�28�(very�severe�eczema).�The�proposed�banding�for�POEM�scores�are:�0–2�(clear/almost� clear);�3–7�(mild);�8–16�(moderate);�17–24�(severe);��25–28�(very�severe).7� †Pruritus�NRS�scores�range�from�0�(no�itch)�to�10�(worst�itch�imaginable).�The�proposed�banding�for�NRS�scores�are:�<3�(mild�itch); �>6.9�(severe�itch);�>9.0�(very�severe�itch).8 A) B) Patient reported flares, POEM, and pruritus NRS • �A�total�of�56.2%�patients�were�currently�experiencing�a�flare,�and�38.3%� experienced�more�than�two�flares�over�the�past�month. � –��Of�those�experiencing�at�least�one�flare�over�the�last�month,�65.1%�and�21.9%� had�partial�or�no�recovery�of�their�most�recent�flares�(Table 2). • �Mean�POEM�score�over�the�last�week�was�10.3�(POEM�scores�range�from�0–28,� with�higher�scores�indicating�more�severe�eczema),�with�57.6%� reporting�moderate�to�very�severe�symptoms�based�on�POEM�scores�of�8�or� greater.�23.3%�of�patients�reported�sleep�disturbance�for�at�least�3�days�out�of� 7�days.�The�mean�pruritus�NRS�score�for�the�worst�itch�during�the�previous� 24�hours�was�5.1�(pruritus�NRS�scores�range�from�0�(no�itch)�to�10�(worst� itch�imaginable). • �At�baseline,�the�number�of�flares�correlated�with�the�POEM�categories�and� POEM�sleep�disruption�days,�pruritus�NRS�itch�at�worst�moment,�and�pruritus� NRS�overall�itch�(correlation�coefficient�0.5172,�0.4061,�0.4250�and�0.4694,� respectively;�all�P�<�0.001).� • �Mean�POEM�and�pruritus�NRS�scores�for�worst�itch�and�itch�overall�were� significantly�higher�in�those�experiencing�a�flare�versus�those�not�experiencing� a�flare�(all�P�<�0.001)�(Figure�2).�Among�those�experiencing�a�flare,�33.2%�of� patients�reported�sleep�disturbance�for�at�least�3�out of�7�days. DLQI, TSQM and WPAI • �Twenty-two�percent�of�patients�reported�that�AD�had�a�very�or�extremely�large� effect�on�quality�of�life�(QoL),�while�the�TSQM�score�for�global�satisfaction�was� 60.2�(TSQM�scores�range�from�0–100,�with�higher�scores�representing�better� satisfaction).�Among�working�patients�(78.8%),�work�productivity�loss�in�the�past� 7�days�was�6.1�hours�(Table�3). • �Outcomes�were�worse�for�patients�experiencing�flares�compared�with�those�not� experiencing�flares�according�to�DLQI�(8.60�vs�3.67,�respectively;�P�<�0.001),�all� four�TSQM�domains�and�WPAI,�except�for�hours�missed�from�work�for�all�patients� and�patients�who�missed�work�(Figure 3). 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