Definitions of non-response and response to biological therapy for severe asthma: a systematic review

Abstract

BackgroundBiologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined, and evaluated definitions of non-response and response to biologics for severe asthma.MethodsWe searched four bibliographic databases from inception to 15th March 2021 (PROSPERO: CRD42021211249).Two reviewers screened references, extracted data, assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). Modified GRADE approach and narrative synthesis were undertaken.ResultsThirteen studies reported three composite outcome measures, three measures of asthma symptoms, one asthma control and one quality of life. Only four were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10/17 (58.8%) were based on Minimal Clinically Important Difference (MCID) or Minimal Important Difference (MID) and 16/17 (94.1%) had high quality evidence. Results were limited by poor methodology for development process and incomplete reporting of psychometric properties. Most measures rated “very low” to “low” for quality of measurement properties and none met all quality standards.ConclusionThis is the first review to synthesize evidence about definitions of response to biologics for severe asthma. While high quality definitions are available, most are MCIDs or MIDs which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database

“…Unfortunately, some severe asthma patients do not respond to biologic therapy, thus presenting asthma exacerbations or deterioration. The differences in treatment response may be multifactorial, and related to various drug and/or patient-related factors, such as the mechanisms of action, the target, dose and interval of the biological drug or the heterogeneity of asthma phenotypes and underlying endotypes [ 49 , 50 ]. Persistent suboptimal responders require a re-evaluation of asthma phenotype biomarkers, and the suspected immunological pathways involved in the asthma inflammation [ 51 ].…”

Severe Asthma and Biological Therapies: Now and the Future

“…Among them, 16 (94.1%) had a high quality of evidence and 58.8% were based on the minimum clinically important difference, which could be insufficient in justifying the continuation of treatment in terms of cost-effectiveness. It would be necessary to include all those involved (organization, clinicians, patients) in order to develop universally acceptable criteria that would help to evaluate the efficacy of new therapies and improve clinical decision making and patient care [ 123 ].…”

Severe asthma: follow-up after one year from the Italian Registry on Severe Asthma (IRSA)

“…The slight differences in the choice of second-line treatment after switching, between IRSA and UKSAR, can be justified by the different characteristics of SA in UKSAR, compared with SA in IRSA, e.g., higher frequency of OCS maintenance therapy (55.2%) and exacerbations (median number in the last 12 months: 5), lower frequency of atopy (52.9%) (9). Conversely, no withdrawals of biologic therapy were observed in IRSA over one year of follow-up, suggesting the possibility to catch a late therapeutic efficacy (30). A significant improvement of asthma outcomes was also observed in patients not treated with biologics.…”