Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

Abstract

During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma, resulting in a revolution in disease control and medical history. These treatments include monoclonal antibodies, recombinant cytokines and fusion proteins, with the former to be, at the moment, the only approved biological therapy for severe refractory asthma, also included in the disease recommendations. 1 To date, five monoclonal antibodies have been approved for the treatment of asthma. Omalizumab, the first biologic drug approved for the treatment of severe allergic asthma, is a recombinant humanized monoclonal antibody that selectively targets circulating IgE and blocks it from binding to its receptor found on mast cells and basophils. Omalizumab interrupts the IgE mediated asthma inflammatory cascade at an early stage 2 and thus, interrupts both early and late asthmatic responses. 3,4 Mepolizumab and reslizumab both target IL-5, which is a key component in eosinophil proliferation, activation and recruitment, preventing consequently its binding to the α-chain of the IL-5 receptor (IL-5α) on eosinophils. 5,6 Benralizumab targets directly IL-5Rα in all cells that express the receptor, such as eosinophils, basophils and mast cells, resulting not only in the blockade of IL-5 mediated survival of these cells but also in a direct eosinophil apoptosis augmentation, via antibody-dependant cell-mediated cytotoxity (ADCC) induced by the enhanced activation of the FcγRIIIa part of the IL-5Rα receptor of mature natural-killer (NK) cells and macrophages, leading in a near depletion of peripheral eosinophils. 7,8 All three

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

“…Recent review articles proposed an algorithm to determine the strategy for switching between biologics in patients with severe asthma. 39 Most of the reports have suggested an evaluation period of approximately 4 months. A previous real-world study reported that the efficacy became fixed at 16 weeks in 80% of the cases and within 24 weeks in 90% of the cases.…”

“…The algorithm recommends switching to omalizumab for patients with atopic manifestations and/or urticaria and switching to dupilumab for patients with FeNO ≥ 25 (ppb) and/or atopic dermatitis. 39 Accordingly, in patients who have residual asthma symptoms despite treatment with a biologic, it is reasonable to switch to other biologics based on positivity for predictive biomarkers and patient characteristics.…”

Treating severe asthma: Targeting the IL‐5 pathway

“…Conversely, a lower proportion of atopic asthma can be classified as eosinophilic. 67 Even though there are no guidelines available that provide the efficacy and safety profile of switching among different monoclonal antibodies, a recent review of Papaioannou et al, 68 provides a general overview of different possibilities of switching. Thereby taking into account a summary of clinical, functional and laboratory biomarkers now available, in order to guide clinicians to choose to switch biologics when it is needed and obtain a more efficient response.…”

Real‑life Cretan asthma registry focused on severe asthma: On behalf of ‘The Cretan registry of the use of Biologics in Severe Asthma’

“…However, further understanding is needed on how and when to switch from one biological therapy to another (32). A simple algorithm on switching possibilities in case that the physicians' initial choice is proven not to be the best has been recently suggested by a Greek expert group (33). Moreover, the clinical approach for choosing an initial biologic, the assessment of response to biologics, and the process of troubleshooting and adjusting biologic treatment for those patients with suboptimal responses are discussed in the recent literature (34).…”