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The International TREatment of ATopic Eczema (TREAT) Registry Taskforce: An Initiative to Harmonize Data Collection across National Atopic Eczema Photo- and Systemic Therapy Registries

2017; Elsevier BV; Volume: 137; Issue: 9 Linguagem: Inglês

10.1016/j.jid.2017.05.014

1523-1747

Phyllis I. Spuls, Louise A. A. Gerbens, Christian Apfelbacher, Dmitri Wall, B.W.M. Arents, S. Barbarot, Amanda Roberts, Mette Deleuran, Maritza A. Middelkamp‐Hup, Christian Vestergaard, Stephan Weidinger, Jochen Schmitt, Alan D. Irvine, Carsten Flohr,

Food Allergy and Anaphylaxis Research

There is an urgent need for immunomodulatory treatments for patients with atopic eczema (AE) (i.e., atopic dermatitis), in particular for those with disease recalcitrant to topical therapies. The only conventional systemic therapy approved by the European Medicines Agency is cyclosporine, and that is approved only for adults. In the United States, only oral corticosteroids and dupilumab have Food and Drug Administration approval. At present, the main evidence to inform clinical practice around conventional systemic immunomodulatory treatments is derived from a rather small body of randomized controlled trials (Roekevisch et al., 2014Roekevisch E. Spuls P.I. Kuester D. Limpens J. Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review.J Allergy Clin Immunol. 2014; 133: 429-438Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar) and case series (Garritsen et al., 2015Garritsen F.M. Roekevisch E. van der Schaft J. Deinum J. Spuls P.I. de Bruin-Weller M.S. Ten years experience with oral immunosuppressive treatment in adult patients with atopic dermatitis in two academic centres.J Eur Acad Dermatol Venereol. 2015; 29: 1905-1912Crossref PubMed Scopus (33) Google Scholar, van der Schaft et al., 2015van der Schaft J. Politiek K. van den Reek J.M. Christoffers W.A. Kievit W. de Jong E.M. et al.Drug survival for ciclosporin A in a long-term daily practice cohort of adult patients with atopic dermatitis.Br J Dermatol. 2015; 172: 1621-1627Crossref PubMed Scopus (60) Google Scholar). Despite this, in the absence of approved alternatives, immunomodulatory treatments are frequently prescribed as off-label therapies in children and adults, as shown in our recent European and North American surveys (Proudfoot et al., 2013Proudfoot L.E. Powell A.M. Ayis S. Barbarot S. Baselga Torres E. Deleuran M. et al.The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.Br J Dermatol. 2013; 169: 901-909Crossref PubMed Scopus (83) Google Scholar, Taylor et al., 2016Taylor K. Swan D.J. Affleck A. Flohr C. Reynolds N.J. U.K. Translational Research Network in Dermatology and the U.KDermatology Clinical Trials Network. Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists.Br J Dermatol. 2016; 176: 1617-1623Crossref Scopus (22) Google Scholar, Totri et al., 2017Totri C.R. Eichenfield L.F. Logan K. Proudfoot L. Schmitt J. Lara-Corrales I. et al.Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: The PeDRA TREAT survey.J Am Acad Dermatol. 2017; 76: 281-285Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar). Inclusion criteria for clinical trials are stringent; research in psoriasis suggests that around 30% of patients on systemic therapies entered into registries (in itself a very select subgroup of all patients on systemic therapy) would not be eligible for a clinical trial, underscoring the value of real world patient data (Garcia-Doval et al., 2012Garcia-Doval I. Carretero G. Vanaclocha F. Ferrandiz C. Dauden E. Sanchez-Carazo J.L. et al.Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials.Arch Dermatol. 2012; 148: 463-470Crossref PubMed Scopus (138) Google Scholar). With the dawn of a new therapeutic era of biologic therapies for AE, dupilumab has shown great promise in placebo-controlled studies and has been approved by the US Food and Drug Administration (Beck et al., 2014Beck L.A. Thaci D. Hamilton J.D. Graham N.M. Bieber T. Rocklin R. et al.Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.N Engl J Med. 2014; 371: 130-139Crossref PubMed Scopus (936) Google Scholar, Simpson et al., 2016Simpson E.L. Bieber T. Guttman-Yassky E. Beck L.A. Blauvelt A. Cork M.J. et al.Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.N Engl J Med. 2016; 375: 2335-2348Crossref PubMed Scopus (1106) Google Scholar, Thaci et al., 2016Thaci D. Simpson E.L. Beck L.A. Bieber T. Blauvelt A. Papp K. et al.Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.Lancet. 2016; 387: 40-52Abstract Full Text Full Text PDF PubMed Scopus (412) Google Scholar); however, we need more evidence with regard to the effectiveness, safety, and cost effectiveness of such therapies compared with currently used treatment modalities, such as phototherapy and conventional systemic immunomodulatory drugs (cyclosporine, methotrexate, azathioprine, and others). Apart from the need for comparative real life clinical data of conventional and new therapies, clinical decision making requires long-term follow-up data on such treatments to generate information on disease control/disease trajectory modification (even after treatment has been discontinued) and drug safety, including rare adverse events. Generation of reliable data to address these issues requires observation of large patient cohorts for several years. Comprehensive health economic evaluation of these different treatments is routinely required by many national health technology assessment organizations and third party payers to inform the allocation of health care resources. Consequently, independent prospective multicenter registries are a logical step, as has been successfully developed for psoriasis. This is all the more important in the light of emerging evidence that suggests that industry-funded postmarketing studies, which are often conducted to detect rare adverse events, are not improving drug safety surveillance (Spelsberg et al., 2017Spelsberg A. Prugger C. Doshi P. Ostrowski K. Witte T. Husgen D. et al.Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.BMJ. 2017; 356: j337Crossref PubMed Scopus (27) Google Scholar). The international TREatment of ATopic eczema (TREAT) Registry Taskforce (www.treat-registry-taskforce.org) seeks to find consensus on core domains and domain items for AE research registries and to harmonize collection of data on patients receiving systemic immunomodulatory therapies, following recently published best-practice guidelines of the European Commission-funded PAtient REgistries iNiTiative (i.e., PARENT) joint action (http://ec.europa.eu/health//sites/health/files/ehealth/docs/patient_registries_guidelines_en.pdf) (Zaletel and Kralj, 2015Zaletel M. Kralj M. Methodological guidelines and recommendations for efficient and rational governance of patient registries. National Institute of Public Health, Slovenia2015Google Scholar). PARENT was a collaborating partner of the TREAT Registry Taskforce. This approach will reduce heterogeneity between national registries, enhance interoperability of the national registries, allow direct comparability of individual country data, and facilitate data pooling between countries. It will also help establish compatible data entry platforms. As a first step on this journey, we recently conducted an international eDelphi exercise and a consensus meeting among 410 dermatologists, nurses, nonclinical researchers involved in AE, pharmaceutical industry representatives, regulatory body representatives, and patients from 36 countries, including members of the International Eczema Council, the European Taskforce for Atopic Dermatitis, and the International Society for Atopic Dermatitis (http://www.comet-initiative.org/studies/details/825?results=true). The study identified a core set of domains and domain items to be captured by national AE patient registries (the “What” to measure) (Table 1) (Gerbens et al., 2017Gerbens L.A. Boyce A.E. Wall D. Barbarot S. de Booij R.J. Deleuran M. et al.TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema registries.Trials. 2017; 18: 87Crossref PubMed Scopus (22) Google Scholar). Further work is currently underway to define how these domains and domain items should be measured (the “How” to measure).Table 1Core set of domains and domain items to be captured in national atopic eczema registries1Results may slightly change after the upcoming “How” to measure meeting.DomainsDomain ItemsDemographicsDate of birth and date of enrolment into registryGenderEthnicityEducational statusCurrent occupation or educationAE diagnosisHow AE diagnosis is establishedUse of validated diagnostic criteriaDate of AE onsetPast AE treatmentsPhototherapySystemic therapyTopical treatments for AEDay hospital care treatments for AE (outpatient)Previous hospitalization for AECurrent AE treatmentsPhototherapySystemic therapyTopical treatmentsAmount of topical creams/ointments used per weekFamily history of AE or allergic diseasesFamily history of AE or allergic diseasesAllergic comorbiditiesAsthmaAllergic rhinoconjunctivitisAtopic eye diseaseEosinophilic oesophagitisFood allergiesContact allergiesOther comorbiditiesMalignanciesSerious infectionsCurrent concomitant medication (i.e., other than specific AE medication)Antihistamines, oral or topicalAntibiotics, oral and topicalImmunosuppressives for other inflammatory diseasesBaseline general AE questionsExposures that trigger disease flaresEpisodes of skin infection (i.e., folliculitis, HSV, molluscum contagiosum)Days lost from school/college/workBaseline physical examinationFitzpatrick skin typeSkin examinationBaseline physician- and patient-reported domainsPhysician-assessed clinical signsInvestigator/physician global assessmentPatient-reported symptomsPatient global assessmentGeneric quality of life scoreSkin-specific quality of life scorePatient-reported satisfaction with AE care receivedImpact of AE on the familyBaseline investigations and assessmentsMedical history (tuberculosis, HIV, hepatitis B or C)Full blood countLiver functionKidney profileEvaluating TPMT level before azathioprine useBaseline managementReasons for choosing specific treatment (systemic or phototherapy)Recording of relative contraindication(s) for selected treatmentFollow-up general AE questionsDays lost from school/college/workChange in diagnosis after enrolment (e.g., from AE to CTCL)Date of death and relation to AEFollow-up physical examinationSkin examinationFollow-up physician- and patient-reported domainsPhysician-assessed clinical signsInvestigator/physician global assessmentPatient-reported symptomsPatient global assessmentGeneric quality-of-life scoreSkin-specific quality-of-life scoreReporting of disease controlAdherence to treatment between appointmentsPatient-reported satisfaction with AE care receivedImpact of AE on the familyFollow-up investigations and assessmentsSafety bloodsFollow-up adverse eventsSerious adverse eventsAdverse events that cause stop or switch of therapy or change in dosageFor (serious) adverse events: probability of relationship with AE treatmentFollow-up managementReason for switching therapyReason for discontinuation of therapyAbbreviations: AE, atopic eczema; CTCL, cutaneous T-cell lymphoma; HSV, herpes simplex virus; TPMT, thiopurine methyltransferase.1 Results may slightly change after the upcoming “How” to measure meeting. Open table in a new tab Abbreviations: AE, atopic eczema; CTCL, cutaneous T-cell lymphoma; HSV, herpes simplex virus; TPMT, thiopurine methyltransferase. We envisage that eligible patients will be children and adults diagnosed with AE who are beginning photo- or systemic immunomodulatory therapy (conventional immunosuppressive therapies as well as new biologics), taking into account the national and local eligibility criteria for these specific therapies. Patients receiving intensive topical therapy or screen failures for systemic therapy may also be included. Patients will be followed up independently of stopping therapy or subsequent switch to other therapies. We look forward to working with the global dermatology community on this project, especially those who routinely treat patients with recalcitrant AE, a disease that accounts for more than 20% of total health loss due to skin conditions (Hay et al., 2014Hay R.J. Johns N.E. Williams H.C. Bolliger I.W. Dellavalle R.P. Margolis D.J. et al.The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions.J Invest Dermatol. 2014; 134: 1527-1534Abstract Full Text Full Text PDF PubMed Scopus (783) Google Scholar) and that has shown a health economic impact similar to that of diabetes mellitus and asthma (Williams et al., 2008Williams H. Stewart A. von Mutius E. Cookson W. Anderson H.R. International Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study Groups. Is eczema really on the increase worldwide?.J Allergy Clin Immunol. 2008; 121 (e15): 947-954Abstract Full Text Full Text PDF PubMed Scopus (410) Google Scholar). Ultimately, national cohorts of AE patients on photo- and systemic immunomodulatory therapies will inform treatment guidelines and will also act as a resource for biomarker discovery and pharmacogenetic and pharmacodynamic research. With more biologic therapies soon to enter our clinical practice, the timing for this project could not be better. Gerbens, Louise A.A. http://orcid.org/0000-0002-5244-5058 Arents, Bernd WM http://orcid.org/0000-0001-6884-8014 Irvine, Alan http://orcid.org/0000-0002-9048-2044 Spuls, Phyllis I http://orcid.org/0000-0002-6035-2863 AI has served as a consultant to Anacor, Chugai Pharma, Pfizer, Regeneron, Roche/Genentech, Sanofi-Genzyme, and UCB Pharma. CV has advised and given lectures for AbbVie, Chugai, Novartis, Regeneron, Sanofi-Genzyme, and UCD Pharma. JS has the lead over the German atopic eczema registry (TREAT Germany) and has received institutional funding for investigator-initiated research from ALK, MSD, Novartis, Pfizer, Sanofi, and Wyeth. MD has been a speaker, advisory board member, and (principal) investigator for AbbVie, CK-Care Foundation, La Roche Posay Laboratoire Dermatologique, Leo Pharma, Meda Pharma, Pierre Fabre Laboratories, Regeneron, Roche, and Sanofi-Genzyme. PS has served as a consultant to AbbVie, Anacor, Leo Pharma, and Novartis; has received independent research grants from Leo Pharma and Schering-Plough; and has been involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of AE. SB has received research grants from La Fondation pour la Dermatite Atopique and Pierre Fabre Laboratories; has received personal fees from Bioderma, Ferring, La Roche Posay Laboratoire Dermatologique, Novalac, and Sanofi-Genzyme, and has received nonfinancial support from AbbVie, Janssen, and Novartis. SW has served as a consultant to Astellas, Novartis, and Sanofi-Genzyme; has received independent research grants from Biogen, Novartis, and Pfizer; and has been involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of AE. CF has advised Roche/Genentech and Sanofi/Regeneron. The authors state no other conflicts of interest. We would like to acknowledge the Dutch atopic eczema patient society (VMCE, Vereniging voor Mensen met Constitutioneel Eczeem), the UK National Eczema Society, and the Irish Skin Foundation for their support.