What trials do and do not tell us about treatments for severe asthma

As understanding of asthma develops, so too does treatment. 1 Bush A Pavord ID Forthcoming UK asthma guidelines: an opportunity to improve asthma outcomes. Lancet. 2021; 398: 1856-1858 Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar Four predominant drug types have been used over the past 100 years: anticholinergics, bronchodilators, corticosteroids and, more recently, specifically targeted asthma treatments—eg, anti-immunoglobulin E and those aimed at broader type 2 inflammation. 2 Chu EK Drazen JM Asthma: one hundred years of treatment and onward. Am J Respir Crit Care Med. 2005; 171: 1202-1208 Crossref PubMed Scopus (78) Google Scholar , 3 Holgate ST A brief history of asthma and its mechanisms to modern concepts of disease pathogenesis. Allergy Asthma Immunol Res. 2010; 2: 165-171 Crossref PubMed Scopus (59) Google Scholar Inhaled corticosteroids (ICS) have remained the mainstay of asthma treatment since the 1970s following a trial published in The Lancet showing steroid-naive patients with moderate to severe asthma could be controlled with ICS. 4 British Thoracic and Tuberculosis Association Inhaled corticosteroids compared with oral prednisone in patients starting long-term corticosteroid therapy for asthma. A controlled trial by the British Thoracic and Tuberculosis Association. Lancet. 1975; 2: 469-473 PubMed Google Scholar Existing asthma treatment is stepwise, increasing doses of ICS for severe eosinophilic asthma even though with increasing doses comes increases in side-effects and responses to increasing steroid treatment are sometimes poor. 5 Global Initiative for Asthma 2023 GINA main report.. https://ginasthma.org/2023-gina-main-report/Date accessed: October 16, 2023 Google Scholar With the benefit of time and data, as we learn more about long-term risks and benefits of asthma treatments and think in terms of disease phenotypes and personalised medicine, clinicians increasingly tailor treatment, focusing on subgroups of people with disease and targeting minutia within inflammatory pathways. 6 Porsbjerg C Melén E Lehtimäki L Shaw D Asthma. Lancet. 2023; 401: 858-873 Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar Increasingly, biologics—eg, omalizumab, mepolizumab, and benralizumab—are prescribed for people with severe asthma and might facilitate a dose reduction in ICS. 7 Agache I Rocha C Beltran J et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: a systematic review for the EAACI Guidelines—recommendations on the use of biologicals in severe asthma. Allergy. 2020; 75: 1043-1057 Crossref PubMed Scopus (82) Google Scholar , 8 Jackson DJ Heaney LG Humbert M et al. Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study. Lancet. 2024; 403: 271-281 Google Scholar Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 studyThese findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control. Full-Text PDF Open Access