Disease characteristics, comorbidities, treatment patterns and quality of life impact in children

Abstract

To the Editor: To address the issue of limited real-world long-term data in children with atopic dermatitis (AD), we designed the PEDISTAD observational study (NCT03687359). This ongoing, international, longitudinal, 5-year registry assesses the disease course, comorbidities, treatment, and disease burden in children with moderate-to-severe AD.1Paller A.S. Guttman-Yassky E. Irvine A.D. et al.Protocol for a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe atopic dermatitis (PEDISTAD): study objectives, design and methodology.BMJ Open. 2020; 10e033507Crossref Scopus (4) Google Scholar Here, we present baseline interim data. The study design and inclusion/exclusion criteria for PEDISTAD have been reported.1Paller A.S. Guttman-Yassky E. Irvine A.D. et al.Protocol for a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe atopic dermatitis (PEDISTAD): study objectives, design and methodology.BMJ Open. 2020; 10e033507Crossref Scopus (4) Google Scholar Briefly, PEDISTAD included children aged <12 years at baseline with investigator-assessed moderate-to-severe disease receiving systemic medications for AD (including biologics, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and corticosteroids), phototherapy, or topical treatment (but otherwise candidates for systemic therapy). Between September 2018 and July 2020, 732 children were enrolled at 106 sites in North America (38.4%), Latin America (23.0%), Europe, the Middle East and Africa (30.3%), and Asia-Pacific (8.3%). As shown in Table I, 61.2% of children had ≥1 selected comorbidity at baseline, mainly atopic comorbidities (59.0%). Most (77.2%) were receiving nonsystemic medications for AD at baseline, while 23.1% were receiving systemic medications for AD (Table I).Table IBaseline demographics and clinical characteristicsBaseline characteristics0 to <2 years (n = 77)2 to <6 years (n = 224)6 to <12 years (n = 431)Total (N = 732)Age, y, mean (SD)1.12 (0.50)3.58 (1.09)8.50 (1.74)6.22 (3.18)Sex, male, n (%)49 (63.6)125 (55.8)208 (48.3)382 (52.2)Race, n/N1 (%) White56/77 (72.7)139/214 (65.0)264/413 (63.9)459/704 (65.2) Black or African American8/77 (10.4)24/214 (11.2)58/413 (14.0)90/704 (12.8) Asian6/77 (7.8)27/214 (12.6)59/413 (14.3)92/704 (13.1) Multiple or other7/77 (9.1)24/214 (11.2)32/413 (7.7)63/704 (8.9)Any concomitant AD comorbidity, n (%)24 (31.2)131 (58.5)293 (68.0)448 (61.2) Type 2 comorbidity24 (31.2)130 (58.0)278 (64.5)432 (59.0) Allergic rhinitis4 (5.2)49 (21.9)198 (45.9)251 (34.3) Asthma1 (1.3)51 (22.8)153 (35.5)205 (28.0) Food allergy22 (28.6)82 (36.6)138 (32.0)242 (33.1) Allergic conjunctivitis013 (5.8)80 (18.6)93 (12.7) Eosinophilic esophagitis01 (0.4)6 (1.4)7 (1.0) Nasal polyposis006 (1.4)6 (0.8) Anxiety∗Anxiety was collected through the combination of patient reported and medical records.05 (2.2)32 (7.4)37 (5.1) ADD/ADHD01 (0.4)30 (7.0)31 (4.2)Age at AD onset, y, median (IQR)0.3 (0.2-0.5)0.5 (0.3-1.0)1.0 (0.3-4.0)0.7 (0.3-2.0)Nonsystemic medications for AD†Only key nonsystemic AD medications are listed. Some children were on other nonsystemic treatments; eg, coal tar, chlorine.57 (74.0)171 (76.3)337 (78.2)565 (77.2) Topical antibiotics3 (3.9)18 (8.0)40 (9.3)61 (8.3) TCS52 (67.5)154 (68.8)306 (71.0)512 (69.9) TCI11 (14.3)56 (25.0)121 (28.1)188 (25.7) Crisaborole1 (1.3)12 (5.4)17 (3.9)30 (4.1)Systemic medications for AD‡Only key systemic AD medications are listed. Some children were on other systemic medications; eg, antibiotics, antihistamines/antiallergics, folic acid.9 (11.7)50 (22.3)110 (25.5)169 (23.1) Cyclosporine016 (7.1)43 (10.0)59 (8.1) Methotrexate021 (9.4)45 (10.4)66 (9.0) Dupilumab05 (2.2)§Off-label treatment in children aged <6 years old.14 (3.2)19 (2.6) Azathioprine01 (0.4)1 (0.2)2 (0.3) Mycophenolate mofetil01 (0.4)4 (0.9)5 (0.7) Systemic corticosteroids9 (11.7)17 (7.6)12 (2.8)38 (5.2)Phototherapy2 (2.6)5 (2.2)21 (4.9)28 (3.8)EASI, mean (SD) [0-72]¶Score ranges; low scores indicate good quality of life and better disease control in each case.15.1 (10.3)13.2 (9.3)15.0 (11.3)14.4 (10.7)BSA % affected by AD, mean (SD) [0-100%]¶Score ranges; low scores indicate good quality of life and better disease control in each case.36.4 (20.6)31.7 (20.8)33.6 (21.1)33.3 (21.0)POEM, mean (SD) [0-28]¶Score ranges; low scores indicate good quality of life and better disease control in each case.15.7 (6.6)16.1 (7.5)15.3 (7.2)15.6 (7.2)CDLQI, mean (SD) [0-30]¶Score ranges; low scores indicate good quality of life and better disease control in each case.N/A10.8 (6.0)‖Assessed in children aged 4 to <6 years old (N1 = 117).10.8 (6.9)10.8 (6.7)IDQOL, mean (SD) [0-30]¶Score ranges; low scores indicate good quality of life and better disease control in each case.10.3 (6.1)Assessed in children aged ≤3 years (N1 = 184).N/AN/ACaregiver-assessed worst scratching during the previous 24 hours, NRS, mean (SD) [0-10]¶Score ranges; low scores indicate good quality of life and better disease control in each case.6.0 (2.6)5.9 (2.8)N/A5.9 (2.7)Child-reported worst itching during the previous night, peak pruritus NRS, mean (SD) [0–10]¶Score ranges; low scores indicate good quality of life and better disease control in each case.N/AN/A4.9 (2.9)N/AChild-reported worst itching during the current day, peak pruritus NRS, mean (SD) [0-10]¶Score ranges; low scores indicate good quality of life and better disease control in each case.N/AN/A3.8 (2.7)N/ADFI, mean (SD) [0-30]¶Score ranges; low scores indicate good quality of life and better disease control in each case.11.1 (7.0)12.0 (7.9)10.3 (7.1)10.9 (7.4)AD, atopic dermatitis; ADD, attention deficit disorder; ADHD, attention deficit-hyperactivity disorders; BSA, body surface area; CDLQI, Children’s Dermatology Life Quality Index; DFI, Dermatitis Family Impact; EASI, Eczema Area and Severity Index; IDQOL, Infants' Dermatitis Quality of Life Index; IQR, interquartile range; N/A, not available; NRS, Numerical Rating Scale; POEM, Patient-Oriented Eczema Measure; SD, standard deviation; TCS, topical corticosteroids; TCI, topical calcineurin inhibitors.N1 used to calculate the percentage of race is smaller than N (=732) due to missing values.∗ Anxiety was collected through the combination of patient reported and medical records.† Only key nonsystemic AD medications are listed. Some children were on other nonsystemic treatments; eg, coal tar, chlorine.‡ Only key systemic AD medications are listed. Some children were on other systemic medications; eg, antibiotics, antihistamines/antiallergics, folic acid.§ Off-label treatment in children aged <6 years old.¶ Score ranges; low scores indicate good quality of life and better disease control in each case.‖ Assessed in children aged 4 to <6 years old (N1 = 117).∗∗ Assessed in children aged ≤3 years (N1 = 184). Open table in a new tab AD, atopic dermatitis; ADD, attention deficit disorder; ADHD, attention deficit-hyperactivity disorders; BSA, body surface area; CDLQI, Children’s Dermatology Life Quality Index; DFI, Dermatitis Family Impact; EASI, Eczema Area and Severity Index; IDQOL, Infants' Dermatitis Quality of Life Index; IQR, interquartile range; N/A, not available; NRS, Numerical Rating Scale; POEM, Patient-Oriented Eczema Measure; SD, standard deviation; TCS, topical corticosteroids; TCI, topical calcineurin inhibitors. N1 used to calculate the percentage of race is smaller than N (=732) due to missing values. Mean (SD) body surface area affected by AD was 33.3% (21.0%), Eczema Area and Severity score was 14.4 (10.7), and Patient-Oriented Eczema Measure score was 15.6 (7.2) (Table I) —both consistent with moderate disease —with a high proportion of children suffering daily from dry/rough, itchy, cracked, flaking skin, and affected sleep (Fig 1). Self-reported mean worst itch score during the previous night was 4.9 (2.9) among children aged 6 to younger than 12 years, with slightly higher worst scratching scores in younger children (0-<6 years) (Table I). The mean Infant’s Dermatitis Quality of Life scores of children aged 0 to 3 years was 10.3 (6.1). Those aged 4 to younger than 12 years reported a mean Children’s Dermatology Life Quality Index of 10.8 (6.7) (moderate) (Table I). The overall mean Dermatitis Family Impact score was 10.9 (7.4) (Table I). Overall, these interim baseline data from PEDISTAD show a significant disease burden characterized by itch and impact on sleep, quality of life, and family, demonstrating a substantial impact of AD on children and their caregivers. This could be due to the low use of systemic therapies (<25%), possibly related to the limited treatment options and concerns about adverse effects with long-term immunosuppressant use. Most of the children in PEDISTAD had concomitant atopic comorbidities, which is consistent with previous studies that found an increased prevalence of comorbid asthma, allergic rhinitis, and food allergy among children with moderate-to-severe AD.2Ballardini N. Kull I. Söderhäll C. Lilja G. Wickman M. Wahlgren C.F. Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort.Br J Dermatol. 2013; 168: 588-594Crossref PubMed Scopus (65) Google Scholar,3Ricci G. Patrizi A. Baldi E. Menna G. Tabanelli M. Masi M. Long-term follow-up of atopic dermatitis: retrospective analysis of related risk factors and association with concomitant allergic diseases.J Am Acad Dermatol. 2006; 55: 765-771Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar The median age of disease onset in this PEDISTAD cohort was 8 months. AD is commonly diagnosed before age 5 years and often persists into adulthood.4Margolis J.S. Abuabara K. Bilker W. Hoffstad O. Margolis D.J. Persistence of mild to moderate atopic dermatitis.JAMA Dermatol. 2014; 150: 593-600Crossref PubMed Scopus (191) Google Scholar People with an early onset of AD have a distinct disease progression and an increased risk of developing other atopic comorbidities.5Paller A.S. Spergel J.M. Mina-Osorio P. Irvine A.D. The atopic march and atopic multimorbidity: many trajectories, many pathways.J Allergy Clin Immunol. 2019; 143: 46-55Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar Early-onset AD can therefore have a significant impact on the lives of children and their family for long periods of time. The main limitation of this observational study is the low patient numbers in the youngest age group. In summary, we found a high disease and family burden among children younger than 12 years old with moderate-to-severe AD and with inadequately controlled disease at baseline. There remains a need for effective and safe therapies for long-term disease control in this pediatric population. For a video abstract of this article, see Video 1 (available via Mendeley at https://doi.org/10.17632/kcr4hndftx.1). Dr Paller has been an investigator for AbbVie, AnaptysBio, BMS, Eli Lilly, Galderma, Incyte, LEO Pharma, Janssen, Novartis, Regeneron Pharmaceuticals, Inc, Sanofi; and a consultant for AbbVie, Abeona, Almirall, Asana Biosciences, Boehringer Ingelheim, BridgeBio Pharma, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Galderma, Incyte, InMed Pharmaceuticals, Janssen, LEO Pharma, Lifemax, Novartis, Pfizer, Rapt Therapeutics, Regeneron, Sanofi Genzyme, Sol Gel, UCB. Dr Guttman-Yassky has been investigator for AbbVie, BMS, Eli Lilly, Galderma, Glenmark, GlaxoSmithKline, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi; a consultant for AbbVie, Anacor, Asana Biosciences, Daiichi Sankyo, DBV, Dermira, Eli Lilly, Galderma, Glenmark, GlaxoSmithKline, Kiniksa Pharmaceuticals, Kyowa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron Pharmaceuticals, Inc, Sanofi; received research grants from AbbVie, BMS, Dermira, Galderma, Innovaderm, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi. Dr Schuttelaar has been an advisory board member for Eli Lilly, LEO Pharma, Pfizer, Sanofi Genzyme; an investigator for AbbVie, Novartis, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme; a consultant for Regeneron Pharmaceuticals, Inc; and has received research grants from Novartis, Sanofi Genzyme. Dr Irvine has received honoraria for consultancy from AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai, Dermavant, Eli Lilly, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB. Dr Baselga has been an investigator for AbbVie, Boehringer Ingelheim, Dermira, Eli Lilly, LEO Pharma, Pfizer, Novartis; and a consultant for Almirall, Galderma, Novartis, Pfizer, Pierre-Fabre, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme. Dr Kataoka has received honoraria for lectures and research grants from Sanofi; and research grants from AbbVie, Eli Lilly, LEO Pharma, Maruho, Pfizer, Otsuka. Dr Antila has participated in clinical studies funded by AbbVie, AstraZeneca, EMS, Eurofarma, GlaxoSmithKline, Humanigen, Janssen, Novartis, Sanofi Genzyme; and participated in conferences and consultancy activities for Aché, AstraZeneca, Chiesi, Eurofarma, IPI ASAC Brasil, Sanofi. Dr de Bruin-Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Eli Lilly, Galderma, Janssen, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme, UCB. Dr Marcoux has been investigator for AbbVie, Amgen, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer; a consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme, UCB; and a speaker for AbbVie, Amgen, BMS, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme. Dr Abramova was an employee of Regeneron Pharmaceuticals, Inc when the study was conducted and may hold stock and/or stock options in the company. Dr Rizova was an employee of Sanofi Genzyme when the study was conducted and may hold stock and/or stock options in the company. Mr Liu is an employee of Tigermed-BDM Inc. and is working as a consultant with Sanofi. Dr Zhang is an employee of Sanofi Genzyme and may hold stock and/or stock options in the company. Medical writing and editorial assistance were provided by Yunyu Huang, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Download .docx (.03 MB) Help with docx files Video script