Abstract

Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors.

Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015-2020) or the CHRONICLE Study (2018-2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups.

Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti-IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti-IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization.

Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.

Keywords: biologics; cohort study; international; management; prescribing; severe asthma.

Conflict of interest statement

Andrew N. Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Roche, Sanofi and Teva, and has received speaker fees from AstraZeneca, Novartis, Teva, and Sanofi. He has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva. He has had consultancy agreements with AstraZeneca and Sanofi. Claire McBrien has attended an international conference with Boehringer Ingelheim and a national meeting with TEVA. Celeste M. Porsbjerg has attended advisory boards for AstraZeneca, Novartis, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from Astra Zeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme. Mona Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline. Anna von Bülow reports speakers fees and consultancy fees from AstraZeneca and Novartis, outside the submitted work. She has also attended advisory board for Novartis. Borja G. Cosio declares grants from Chiesi and GSK; personal fees for advisory board activities from Chiesi, GSK, Novartis, Sanofi, Teva, and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, GSK, Menarini, and AstraZeneca, outside the submitted work. Liam G. Heaney declares he has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva; he has received grants from MedImmune, Novartis UK, Roche/Genentech Inc, and Glaxo Smith Kline, Amgen, Genentech/Hoffman la Roche, Astra Zeneca, MedImmune, Glaxo Smith Kline, Aerocrine and Vitalograph; he has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Napp Pharmaceuticals; he has also taken part in asthma clinical trials sponsored by Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. Mark Hew declares grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects. David J Jackson has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva, Napp, Chiesi, Novartis, Sanofi and research grant funding from AstraZeneca. Stelios Loukides received honorarium form Novartis, Astra, GSK; received grants from GSK. Njira Lugogo received consulting fees for advisory board participation from Amgen, AstraZeneca, Genentech, GSK, Novartis, Regeneron, Sanofi, and Teva; honoraria for non-speakers bureau presentations from GSK and Astra Zeneca; and travel support from Astra Zeneca and GSK; her institution received research support from Amgen, AstraZeneca, Avillion, Evidera, Gossamer Bio, Genentech, GSK, Janssen, Regeneron, Sanofi, Novartis and Teva. She is an honorary faculty member of Observational and Pragmatic Research Institute (OPRI) but does not receive compensation for this role. Andriana I Papaioannou has received fees and honoraria from Menarini, GSK, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi. Désirée Larenas Linnemann reports personal fees from Allakos, Amstrong, Astrazeneca, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Gossamer, Carnot and grants from Sanofi, Astrazeneca, Novartis, Circassia, GSK, Purina institute, Abvvie, Lilly, Pfizer, outside the submitted work. Wendy C. Moore is on advisory boards for and reports grant and personal fees from AstraZeneca, Sanofi Regeneron, Genentech, Gossamer Bio Inc, Cumberland NHLBI/NHLBI, and GlaxoSmithKline. She is also a member of the writing and steering committee for the CHRONICLE study as well as a PI of the clinical trial at Wake Forest.). Luis Perez-de-Llano declares non-financial support, personal fees, and grants from Teva; non-financial support and personal fees from Boehringer Ingelheim, Esteve, FAES, GlaxoSmithKline, Mundipharma, and Novartis; personal fees and grants from AstraZeneca and Chiesi; personal fees from Sanofi, MSD, Techdow Pharma Leo-Pharma, GEBRO, and GILEAD; and non-financial support from Menarini outside the submitted work. Linda M. Rasmussen declares speakers fees from AstraZeneca, Boehringer Ingelheim, TEVA, ALK, GlaxoSmithKline, and Mundipharma, outside the submitted work and attended advisory board for AstraZeneca, Sanofi and Teva. Salman Siddiqui declares personal fees from AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Knopp Biosciences, CSL Behring, Mundipharma, ERT Medical, Owlstone Medical, Boehringer Ingelheim, outside the submitted work. Christopher S. Ambrose and Trung N. Tran are employees of AstraZeneca, sponsor and funder of the CHRONICLE study and a co-funder of the International Severe Asthma Registry. Esther Garcia Gil and Marianna Alacqua were employees of AstraZeneca at the time this study was completed. Charlotte Suppli Ulrik has attended advisory boards for AstraZeneca, ALK-Abello, GSK, Boehringer-Ingelheim, Novartis, Chiesi, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Sandoz, Mundipharma, Chiesi, Boehringer-Ingelheim, Orion Pharma, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, Merck, InsMed, ALK-Abello, Sanofi-Genzyme, GlaxoSmithKline, Boehringer-Ingelheim, Regeneron, Chiesi and Novartis; and has received educational and research grants from AstraZeneca, MundiPharma, Boehringer-Ingelheim, Novartis, TEVA, GlaxoSmithKline and Sanofi-Genzyme. John W. Upham has received speaker fees and consulting fees from Novartis, AstraZeneca, GSK, Sanofi, and Boehringer Ingelheim. Eileen Wang has received honoraria from AstraZeneca, GlaxoSmithKline, Clinical Care Options, and Wefight. She has been an investigator on clinical trials sponsored by AstraZeneca, Optimum Patient Care, Sanofi, Sema4, GlaxoSmithKline, Genentech, Novartis, Teva, and National Institute of Allergy and Infectious Diseases (NIAID) for which her institution has received funding. Karin Dahl Assing, Susanne Hansen, Maria Kallieri, Johannes Schmid, John Busby, J. Mark FitzGerald, and Ruth B. Murray declare no relevant conflicts of interest concerning this paper. Victoria A. Carter and Chris A. Price are employees of Optimum Patient Care Global, a co-funder of the International Severe Asthma Registry. Neva Eleangovan is an employee of the Observational and Pragmatic Research Institute (OPRI), which conducted this study in collaboration with Optimum Patient Care and AstraZeneca. OPRI has also conducted paid research in respiratory disease on behalf of the following other organisations in the past 3 years: Aerocrine, AKL Research and Development Ltd, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mapi Group, Meda, Mylan, Mundipharma, Napp, Novartis, Orion, Regeneron, Roche, Takeda, Teva, and Zentiva (a Sanofi company). Lakmini Bulathsinhala, Isha Chaudhry, and Bindhu Unni were employees of the Observational and Pragmatic Research Institute, which conducted this study in collaboration with Optimum Patient Care and AstraZeneca. David Price has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The authors report no other conflicts of interest in this work.