What to do when your adult patient with severe asthma does not respond to a biologic

Background: Asthma management has been revolutionized by the introduction and expansion of biologic therapies. Since the approval of omalizumab for allergic asthma in 2003, six additional biologics with an asthma indication have been FDA-approved, and several more are in late-phase development. The clinical challenge is that all of these therapies reduce exacerbations, but asthma exacerbations are difficult to predict. A subgroup of 20-40% of biologic-treated patients will achieve asthma remission, or near remission depending on the criteria used, during biologic therapy, an ideal outcome. For the remaining 60-80% of treated patients, the benefits are evident but usually less defined or quantifiable. Symptoms often improve, but patient-reported outcomes lack precision to verify efficacy. All biologic therapies reduce exacerbations by an average of 50%; they do not eliminate exacerbations for most patients. In long-term, unblinded, safety trials, the majority of treated subjects have zero to one exacerbation per year. Thus, for an individual patient, assessing response and predicting response can be problematic, and strategies for addressing suboptimal responses are not standardized. Methods: This article summarizes a potential approach to use when biologic therapy in adults with asthma is, or appears to be, insufficiently effective. Results: The major points are: 1) set expectations prior to therapy to facilitate decision making and do not expect remission or near remission depending on criteria used; 2) reassess the source of symptoms and findings with the possibility that the asthma diagnosis is not accurate or co-morbidities are the major contributors to the clinical presentation; 3) evaluate adherence with both small molecule therapy (i.e. inhaled controller therapy) and with the biologic regimen if administered in-home; 4) change the biologic to an alternative biologic, generally affecting a different pathway. Conclusions: This strategy is not a guarantee of success but may assist in clinical decision-making.