Defining a Severe Asthma Super-Responder: Findings from a Delphi Process

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab

“…This novel framework comprised at least 12 months with the absence of significant symptoms by a validated instrument, no OCS use for asthma, optimisation/ stabilisation of lung function, and health care professional (HCP)/patient agreement about disease remission [24]. Upham et al also used a Delphi process to develop a consensus definition for what they dubbed super-response to therapy in severe asthma [33]. The super-response definition comprised improvements in three domains assessed over 12 months, including improvement in at least two of the following major criteria: exacerbation elimination, C 2 9 minimal clinically important difference (MCID) improvements in asthma control, or cessation of long-term OCS; and improvement in one of the following minor criteria: C 75% exacerbation reduction, C 500 mL improvement FEV 1 , or achievement of well-controlled asthma [33].…”

“…Upham et al also used a Delphi process to develop a consensus definition for what they dubbed super-response to therapy in severe asthma [33]. The super-response definition comprised improvements in three domains assessed over 12 months, including improvement in at least two of the following major criteria: exacerbation elimination, C 2 9 minimal clinically important difference (MCID) improvements in asthma control, or cessation of long-term OCS; and improvement in one of the following minor criteria: C 75% exacerbation reduction, C 500 mL improvement FEV 1 , or achievement of well-controlled asthma [33]. Indeed, the criteria for clinical remission are broadly consistent with those for super-response; however, patients with less active disease could be considered super-responders and experience meaningful responses to therapy, while not meeting the stricter definition of clinical remission [24,33].…”

“…A recent post hoc analysis from SIROCCO and CALIMA evaluated the percentages of patients with improvements in six outcomes (exacerbations, ACQ-6 score, FEV 1 , total asthma symptom score [composite of daytime and nighttime symptoms], Asthma Quality of Life Questionnaire [AQLQ], and nights with awakenings that required asthma rescue medication). Of 504 patients with severe asthma treated with benralizumab every 8 weeks (Q8W, first three doses 4 weeks apart), 89.7% (454/504) evidenced a response in one or more outcome measures; however, the analysis did not formally apply either consensus definition [24,33,38].…”

“…The objective of this pooled post hoc analysis was to apply a composite remission definition-described below, and derived from two previously published frameworks (i.e. framework for asthma remission and severe asthma super-responders)-to a pooled population of patients treated with benralizumab in three prior phase 3 pivotal studies to (1) understand individual responses to benralizumab at 6 and 12 months from baseline according to composite remission criteria and (2) determine how many patients may have achieved clinical remission in severe asthma [24,33]. This analysis focused on patients treated with the approved benralizumab regimen to emphasize the importance of considering clinical remission among individuals rather than as a comparison between treatment groups in a clinical trial.…”

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

“…Thus, the definitions of super-responders vary among reports, which result in a range of prevalence (14–39%) and various features of super-responders, although asthma experts recently tried to develop an international consensus on the definition of super-responders using the Delphi process. 34 When we consider discontinuing biologic therapies in patients with severe asthma receiving biologics, super-responders are candidates. Nonetheless, the various definitions of super-responders may make it complicated to identify suitable patients.…”