Longitudinal Disease Trajectories in Remission and Refractory Asthma From REGAIN, A Real-world Multi-center Study

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Abstract RATIONALE: Despite greater understanding of asthma heterogeneity and pathogenesis, real-world longitudinal disease trajectories in the era of biologics and predictors of treatment response remain unclear. The RE al-world and G enomic data-based A sthma I nsights through N etwork analysis (REGAIN) study is an 18-month prospective observational study that combines clinical, genomic, transcriptomic, and mobile health data to address these key knowledge gaps. METHODS: REGAIN enrolled adult patients with mild to severe asthma recruited from the Mount Sinai Health System and National Jewish Health. Subgroups were defined by type 2 (T2) inflammation, asthma control, and treatment at baseline. Study visits occurred at 0-, 6-, and 18-months for all asthma subgroups and an additional 3-month visit for those initiated on biologics. Clinical remission was defined as Asthma Control Test (ACT) ≥ 20, absence of exacerbations and systemic corticosteroids for asthma. RESULTS: Our analyses included 528 adults with asthma. Subgroups were defined as those with T2-high asthma who had: 1) well controlled symptoms on inhaled therapy (T2-high STEP, n=178), 2) partly to well controlled symptoms on biologics (T2-high bio, n=134), 3) uncontrolled symptoms and newly initiated on biologics (T2-high denovo, n=58), and 4) any level of symptom control after previously failing at least 2 biologics (T2-high failed, n=35). A fifth subgroup included those with T2-low asthma with any level of symptom control on inhaled therapy (T2-low STEP, n=105). At baseline, T2-high failed had significantly higher proportions of obesity, gastroesophageal reflux disease (GERD), lower educational status, and longer duration of disease (all P <.01). At 6-months, most participants in T2-high STEP (73.2%) and T2-high bio (64.6%) retained control. In contrast, T2-high failed represented a refractory subgroup with 92.3% uncontrolled at 6 months. For T2-high denovo, after initiation of biologic therapy, 45.5% remained uncontrolled, 25% achieved moderate control, and 29.5% achieved clinical remission. Of those achieving clinical remission, 30.7% were able to significantly reduce inhaled therapy. Clinical remission at 6 months predicted persistence of remission at 18 months. CONCLUSIONS: Early clinical remission at 6 months predicted sustained remission. T2-high failed represented a persistently refractory group despite treatment with different biologics and highlights potentially important risk factors including longer duration of disease, comorbidities of GERD and obesity, and impacts from social determinants of health represented by lower educational status. Understanding these real-world longitudinal disease trajectories enhance our precision medicine insights, allowing improved identification of those at highest risk in addition to those likely to achieve and retain clinical remission.

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