Longitudinal Assessment of Glucocorticoid Toxicity Reduction in Patients With Severe Asthma Treated With Biologic Therapies.

Abstract

Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-related toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI Aggregate Improvement Score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤-10. This study was a longitudinal assessment of patients with SA treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement. A total of 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy. At 3 years, daily prednisolone use continued to decrease (6.9 mg/day [4.0, 9.4] year 1 vs 0.8 mg/day [0.0, 3.7] year 3, P < .001), OCS-related toxicity continued to decline (AIS at 3 years -36 [-94, 19]), and 61% (54 of 89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at years 1 and 3 (ρ 0.65, P < .001). Nearly half (49%) met the AIS MCID at both years 1 and 3, but 29% of the cohort did not meet the AIS MCID at either time point. Toxicity change at year 1 was predictive of toxicity change at year 3 for 79%. Toxicity reduction was not proportional to OCS reduction; there were no prebiologic characteristics that predicted toxicity reduction. After 3 years of biologic treatment, 61% of patients with SA had clinically significant toxicity improvement. Individual toxicity outcomes at year 1 are associated with longitudinal outcomes, suggesting that for some, additional interventions are needed alongside OCS reduction to decrease morbidity.