PMID- 37143849
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240313
IS  - 2312-0541 (Print)
IS  - 2312-0541 (Electronic)
IS  - 2312-0541 (Linking)
VI  - 9
IP  - 3
DP  - 2023 Jul
TI  - Definitions of non-response and response to biological therapy for severe asthma: 
      a systematic review.
LID - 00444-2022 [pii]
LID - 10.1183/23120541.00444-2022 [doi]
AB  - BACKGROUND: Biologics have proven efficacy for patients with severe asthma but 
      there is lack of consensus on defining response. We systematically reviewed and 
      appraised methodologically developed, defined and evaluated definitions of 
      non-response and response to biologics for severe asthma. METHODS: We searched 
      four bibliographic databases from inception to 15 March 2021. Two reviewers 
      screened references, extracted data, and assessed methodological quality of 
      development, measurement properties of outcome measures and definitions of 
      response based on COnsensus-based Standards for the selection of health 
      Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations 
      Assessment, Development and Evaluation) approach and narrative synthesis were 
      undertaken. RESULTS: 13 studies reported three composite outcome measures, three 
      asthma symptoms measures, one asthma control measure and one quality of life 
      measure. Only four measures were developed with patient input; none were 
      composite measures. Studies utilised 17 definitions of response: 10 out of 17 
      (58.8%) were based on minimal clinically important difference (MCID) or minimal 
      important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. 
      Results were limited by poor methodology for the development process and 
      incomplete reporting of psychometric properties. Most measures rated "very low" 
      to "low" for quality of measurement properties and none met all quality 
      standards. CONCLUSIONS: This is the first review to synthesise evidence about 
      definitions of response to biologics for severe asthma. While high-quality 
      definitions are available, most are MCIDs or MIDs, which may be insufficient to 
      justify continuation of biologics in terms of cost-effectiveness. There remains 
      an unmet need for universally accepted, patient-centred, composite definitions to 
      aid clinical decision making and comparability of responses to biologics.
CI  - Copyright (c)The authors 2023.
FAU - Khaleva, Ekaterina
AU  - Khaleva E
AUID- ORCID: 0000-0002-2220-7745
AD  - Clinical and Experimental Sciences and Human Development and Health, Faculty of 
      Medicine, University of Southampton, Southampton, UK.
FAU - Rattu, Anna
AU  - Rattu A
AUID- ORCID: 0000-0002-7497-9552
AD  - Clinical and Experimental Sciences and Human Development and Health, Faculty of 
      Medicine, University of Southampton, Southampton, UK.
FAU - Brightling, Chris
AU  - Brightling C
AUID- ORCID: 0000-0002-9345-4903
AD  - Institute for Lung Health, Leicester NIHR BRC, University of Leicester, UK.
FAU - Bush, Andrew
AU  - Bush A
AUID- ORCID: 0000-0001-6756-9822
AD  - Centre for Paediatrics and Child Health and National Heart and Lung Institute, 
      Imperial College, Royal Brompton Hospital, London, UK.
FAU - Bourdin, Arnaud
AU  - Bourdin A
AUID- ORCID: 0000-0002-4645-5209
AD  - PhyMedExp, University of Montpellier, Montpellier, France.
FAU - Bossios, Apostolos
AU  - Bossios A
AUID- ORCID: 0000-0002-0494-2690
AD  - Department of Respiratory Medicine and Allergy, Karolinska University Hospital 
      and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Chung, Kian Fan
AU  - Chung KF
AUID- ORCID: 0000-0001-7101-1426
AD  - National Heart and Lung Institute, Imperial College London, London, UK.
FAU - Chaudhuri, Rekha
AU  - Chaudhuri R
AUID- ORCID: 0000-0001-8007-949X
AD  - Institute of Infection, Immunity and Inflammation, University of Glasgow, 
      Glasgow, UK.
FAU - Coleman, Courtney
AU  - Coleman C
AUID- ORCID: 0000-0001-7687-1273
AD  - European Lung Foundation, Sheffield, UK.
FAU - Djukanovic, Ratko
AU  - Djukanovic R
AUID- ORCID: 0000-0001-6039-5612
AD  - Clinical and Experimental Sciences and Human Development and Health, Faculty of 
      Medicine, University of Southampton, Southampton, UK.
AD  - NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS 
      Foundation Trust, Southampton, UK.
FAU - Dahlen, Sven-Erik
AU  - Dahlen SE
AUID- ORCID: 0000-0002-4993-4002
AD  - Department of Respiratory Medicine and Allergy, Karolinska University Hospital 
      and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Exley, Andrew
AU  - Exley A
AUID- ORCID: 0000-0002-2628-6129
AD  - Adept Biologica Consulting Limited, London, UK.
FAU - Fleming, Louise
AU  - Fleming L
AUID- ORCID: 0000-0002-7268-7433
AD  - National Heart and Lung Institute, Imperial College London, London, UK.
FAU - Fowler, Stephen J
AU  - Fowler SJ
AUID- ORCID: 0000-0002-4524-1663
AD  - Faculty of Biology, Medicine and Health, School of Biological Sciences, Division 
      of Infection, Immunity and Respiratory Medicine, University of Manchester, NIHR 
      Manchester Biomedical Research Unit, Manchester University NHS Foundation Trust, 
      Manchester, UK.
FAU - Gupta, Atul
AU  - Gupta A
AUID- ORCID: 0000-0002-1610-0335
AD  - Department of Paediatric Respiratory Medicine, King's College Hospital, London, 
      UK.
FAU - Hamelmann, Eckard
AU  - Hamelmann E
AD  - Children's Center Bethel, Department of Pediatrics, University Bielefeld, 
      Bielefeld, Germany.
FAU - Koppelman, Gerard H
AU  - Koppelman GH
AUID- ORCID: 0000-0001-8567-3252
AD  - University of Groningen, University Medical Center Groningen, Beatrix Children's 
      Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, 
      Groningen, The Netherlands.
AD  - University of Groningen, University Medical Center Groningen, Groningen Research 
      Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
FAU - Melen, Erik
AU  - Melen E
AUID- ORCID: 0000-0002-8248-0663
AD  - Department of Clinical Science and Education Sodersjukhuset, Karolinska 
      Institutet, Stockholm, Sweden.
FAU - Mahler, Vera
AU  - Mahler V
AUID- ORCID: 0000-0001-6471-1811
AD  - Division of Allergology, Paul-Ehrlich-Institut, Federal Institute for Vaccines 
      and Biomedicines, Langen, Germany.
FAU - Seddon, Paul
AU  - Seddon P
AUID- ORCID: 0000-0003-2136-958X
AD  - Respiratory Care, Royal Alexandra Children's Hospital, Brighton, UK.
FAU - Singer, Florian
AU  - Singer F
AUID- ORCID: 0000-0003-3471-5664
AD  - Department of Respiratory Medicine, University Children's Hospital Zurich and 
      Childhood Research Center, Zurich, Switzerland.
AD  - Division of Paediatric Pulmonology and Allergology, Department of Paediatrics and 
      Adolescent Medicine, Medical University of Graz, Graz, Austria.
FAU - Porsbjerg, Celeste
AU  - Porsbjerg C
AUID- ORCID: 0000-0003-4825-9436
AD  - Department of Respiratory Medicine, Respiratory Research Unit, Bispebjerg 
      Hospital, Copenhagen, Denmark.
FAU - Ramiconi, Valeria
AU  - Ramiconi V
AD  - European Federation of Allergy and Airways Diseases Patients' Associations, 
      Brussels, Belgium.
FAU - Rusconi, Franca
AU  - Rusconi F
AUID- ORCID: 0000-0002-9544-6472
AD  - Department of Mother and Child Health, Azienda USL Toscana Nord Ovest, Pisa, 
      Italy.
FAU - Yasinska, Valentyna
AU  - Yasinska V
AUID- ORCID: 0000-0002-1379-1265
AD  - Department of Respiratory Medicine and Allergy, Karolinska University Hospital 
      and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Roberts, Graham
AU  - Roberts G
AUID- ORCID: 0000-0003-2252-1248
AD  - Clinical and Experimental Sciences and Human Development and Health, Faculty of 
      Medicine, University of Southampton, Southampton, UK.
AD  - NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS 
      Foundation Trust, Southampton, UK.
LA  - eng
GR  - MR/T010371/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20230502
PL  - England
TA  - ERJ Open Res
JT  - ERJ open research
JID - 101671641
PMC - PMC10152254
COIS- Conflict of interests: E. Khaleva and A. Rattu declare funding for the present 
      manuscript from the 3TR European Union Innovative Medicines Initiative 2 paid to 
      the university. C. Brightling declares grants from GlaxoSmithKline, AstraZeneca, 
      Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic and 
      4DPharma, consulting fees from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, 
      Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic, 4DPharma and Teva, and 
      support from the 3TR project. A. Bourdin reports being an investigator for 
      clinical trials promoted by AstraZeneca, Chieisi, GlaxoSmithKline, Boehringer 
      Ingelheim, Novartis, Regeneron and Sanofi; having received fees for lectures, 
      attendance of meeting and consultancy from AstraZeneca, Chieisi, GlaxoSmithKline, 
      Boehringer Ingelheim, Novartis, Regeneron and Sanofi; having received research 
      grants from AstraZeneca and Boehringer Ingelheim; and participation on a data 
      safety monitoring or advisory board of AB Science. A. Bossios has received 
      lecture fees from GlaxoSmithKline, AstraZeneca, Teva and Novartis; honoraria for 
      advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Novartis and 
      Sanofi; and received support for attending meetings from AstraZeneca and 
      Novartis, all outside the present work; reports being a member of the Steering 
      Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and 
      Chronic Cough) of the European Respiratory Society and Vice-chair of the Nordic 
      Severe Asthma Network (NSAN). K.F. Chung has received honoraria for participating 
      in advisory board meetings of GlaxoSmithKline, AstraZeneca, Roche, Novartis, 
      Merck and Shionogi regarding treatments for asthma, COPD and chronic cough, and 
      has also been renumerated for speaking engagements for Novartis and AstraZeneca. 
      R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, 
      Chiesi, Sanofi and Novartis; honoraria for advisory board meetings from 
      GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis; sponsorship to attend 
      international scientific meetings from Chiesi, Napp, Sanofi, Boehringer, 
      GlaxoSmithKline and AstraZeneca, and a research grant to her Institute from 
      AstraZeneca for a UK multicentre study. C. Coleman declares funding received to 
      support this work by the European Lung Foundation (ELF) from the European 
      Commission's Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant 
      agreement number 831434 (3TR), and is an employee of the ELF. R. Djukanovic 
      declares funding from European Respiratory Society, Teva, GlaxoSmithKline, 
      Novartis, Sanofi and Chiesi for the SHARP CRC, consulting fees for Synairgen; 
      honorarium for a lecture from GlaxoSmithKline, participation on a data safety 
      monitoring board or advisory board for Kymab (Cambridge) and shares in Synairgen, 
      outside the submitted work. S-E. Dahlen declares funding from 3TR IMI Grant; 
      consulting fees from AstraZeneca, Cayman Co., GlaxoSmithKline, Novartis, 
      Regeneron, Sanofi and Teva; honoraria for lectures from AstraZeneca and Sanofi. 
      A. Exley declares being a minority shareholder in GlaxoSmithKline PLC. L. Fleming 
      declares participation in advisory boards and honoraria for lectures from Sanofi, 
      Respiri UK, AstraZeneca, Novartis and Teva, outside the scope of this 
      publication. All payments were made to her institution. A. Gupta received speaker 
      and advisory board fees from GlaxoSmithKline, Novartis, AstraZeneca and 
      Boehringer Ingelheim. A. Gupta's institution had received research grants from 
      GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim. E. Hamelmann 
      declares support from the German Ministry of Education and Research (BMBF) and 
      German Asthma Net (GAN) e.V.; funding for research in severe asthma in children 
      (CHAMP-01GL1742D) and for Severe Asthma Register. G.H. Koppelman reports 
      receiving research grants from the Lung Foundation of the Netherlands, Ubbo 
      Emmius Foundation, H2020 European Union, Teva, GlaxoSmithKline and Vertex, 
      outside this work (money to institution); he reports memberships of advisory 
      boards to GlaxoSmithKline and PURE-IMS, outside this work (money to institution). 
      E. Melen has received consulting fees from AstraZeneca, Chiesi, Novartis and 
      Sanofi outside the submitted work. V. Mahler has no conflict of interest but 
      declares that the views expressed in this review are the personal views of the 
      author and may not be understood or quoted as being made on behalf of or 
      reflecting the position of the respective national competent authority, the 
      European Medicines Agency, or one of its committees or working parties. F. Singer 
      reports being an investigator for clinical trials promoted by Vertex and having 
      received fees for lectures from Vertex and Novartis, outside the submitted work. 
      C. Porsbjerg declares grants, consulting fees and honoraria from AstraZeneca, 
      GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK (paid to institution and 
      personal honoraria); participation in the advisory board for AstraZeneca, 
      Novartis, Teva, Sanofi and ALK, outside the submitted work. V. Ramiconi reports 
      grants paid to EFA from Pfizer, Novartis, AstraZeneca, Sanofi, Chiesi 
      Farmaceutici, Regeneron, DBV Technologies, MSD, GlaxoSmithKline, Aimmune, 
      LeoPharma, AbbVie, Boehringer Ingelheim, OM Pharma and Roche; payment for expert 
      testimony from Novartis Global Respiratory Patient Council 2021 and Novartis EPIS 
      Steering Committee to EFA. G. Roberts declares EU IMI funding and consulting fees 
      from AstraZeneca paid to his institution. No other author has any conflict of 
      interest to declare.
EDAT- 2023/05/05 06:42
MHDA- 2023/05/05 06:43
PMCR- 2023/05/02
CRDT- 2023/05/05 03:52
PHST- 2022/08/30 00:00 [received]
PHST- 2022/12/06 00:00 [accepted]
PHST- 2023/05/05 06:43 [medline]
PHST- 2023/05/05 06:42 [pubmed]
PHST- 2023/05/05 03:52 [entrez]
PHST- 2023/05/02 00:00 [pmc-release]
AID - 00444-2022 [pii]
AID - 10.1183/23120541.00444-2022 [doi]
PST - epublish
SO  - ERJ Open Res. 2023 May 2;9(3):00444-2022. doi: 10.1183/23120541.00444-2022. 
      eCollection 2023 Jul.