Assessing the impact of earlier initiation of biologics on clinical remission and other outcomes in a global real-life severe asthma cohort from CHRONICLE, ISAR and OPCRD.

Abstract

Biologics are generally reserved for severe asthma (SA) after standard treatments have failed. Their recommendation is based on randomized controlled trials, designed to assess efficacy but not the optimal timing for biologic initiation. Does the timing of biologic initiation affect SA outcomes, including remission? This was a cohort study using data from the International Severe Asthma Registry, the CHRONICLE US SA registry, and the UK Optimum Patient Care Research Database, together comprising data from 26 countries. The duration of time to biologic initiation was described using several proxies (e.g., duration of asthma, potential SA [PSA], lung function impairment, and frequent exacerbations, all pre-biologic). The associations between these proxies and clinical remission, exacerbations, asthma control, lung function, and oral corticosteroid (OCS) use were assessed. 9,241 patients were included in the association analyses. Overall, the likelihood of achieving improvement in each outcome post-biologic decreased with increasing time-to-biologic-initiation. The odds of achieving clinical remission 12-months post-biologic initiation were reduced for every 10 years patients had asthma pre-biologic (0.86 [0.84, 0.88], PSA (0.78 [0.63, 0.96]), and lung function impairment (0.24 [ 0.21, 0.28]) and for every 10 grams lifetime cumulative OCS dose (0.54 [0.30, 0.98]). For every 10-years patients had PSA pre-biologic, post-biologic exacerbation rates were 1.08 [1.03, 1.13] times higher, lung function improvement was 2.35% [-3.18, -1.51] less, and the odds of having well- or partly-controlled asthma was 12% lower (0.88 [0.53, 1.47]). Earlier initiation of biologics in individuals with SA is associated with better clinical outcomes, suggesting the need to modify approaches to asthma management from a 'reserve' to a 'preserve' approach: i.e., not reserving biologics for those with long-standing SA, instead preserving patients' lung function and possibly increasing the likelihood of better clinical outcomes with earlier biologic initiation. CHRONICLE - ClinicalTrials.gov identifier: NCT03373045.