The biologics era of asthma began when the Federal Drug Administration approved omalizumab in 2003. Since then, 5 additional biologic therapeutics have been approved: Mepolizumab (2015), Reslizumab (2016), Benralizumab (2017), Dupilumab (2018), and more recently, Tezepelumab (2021). As a class, these monoclonal antibodies are all safe and effective, as demonstrated in the registry trials that varied in length from months to approximately 1 year. However, because of their immunomodulatory effects, propensity for generating antidrug antibodies, and adverse effects noted in the pivotal trials, concern remains about the long-term efficacy and risk, highlighting a need for long-term safety and efficacy data. For example, because all the approved agents modulate Type-2 inflammation, they could be associated with an increased risk of parasitic infection. Fortunately, long-term data continue to accumulate that indicate these medications are not associated with this risk or other long-term adverse events, nor with the development of neutralizing antidrug antibodies. In addition, both long-term follow-up and real-world longitudinal studies demonstrate that as a class, these agents continue to be effective for years in most patients. In this study, we reviewed these long-term data and highlight the questions and controversies associated with each class (Table 1). Table 1Asthma Biologics With Long-Term Follow-up Data Therapy approval Mechanism of action Endotype/ pivotal trial criteria Key efficacy/safety outcomes Notable adverse effects Long-term studies outcomes/ follow-up Omalizumab2003 Humanized mAb inhibits activity of IgE Moderate-severe allergic asthma/IgE ≥ 30 IU/mL, + SPT or specific IgE to perennial allergen Improvement of asthma controlMinimal improvement in lung function Injection site reactionsHypersensitivity reactionsDelayed anaphylaxis 42 observational studies, no open label extension/Over 4 years Mepolizumab2015 Humanized mAb inhibits actions of IL-5 Severe eosinophilic asthma/blood eosinophils ≥ 150 or 300 cells/ul Decrease exacerbations by 39%-52%Weak improvement in FEV1 Injection site reactionsHypersensitivity reactionsHerpes ZosterMyalgias Open label extension studies,COLUMBA, COSMOS, COSMEX/Over 3 y Benralizumab2017 Humanized mAb inhibits actions of IL-5 receptor Severe eosinophilic asthma/blood eosinophils 300 cells/ul Decreased exacerbations by 45%-51%Improvement in pre-bronchodilator FEV1 Injection site reactionsHypersensitivity reactionsmyalgias Open Label ExtensionBORAMELTEMI/Over 5 y Dupilumab2017 Humanized mAb inhibits actions of IL-4 and IL-13 Blood eosinophils ≥ 150/μLFeNO > 25 ppbBlood eos < 1500 cells/ul Decreased exacerbations by 46%-48%Improvement in pre-bronchodilator FEV1 Injection site reactionsConjunctivitisTransient increase in blood eosinophils Open label extensionTRAVERSE/Over 3 y Abbreviations: FEV, forced expiratory volume; Ig, immunoglobulin; IL, interleukin; IU, international units; SPT, skin prick test. Open table in a new tab Abbreviations: FEV, forced expiratory volume; Ig, immunoglobulin; IL, interleukin; IU, international units; SPT, skin prick test.