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

Abstract

Background: 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.

Objective: 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.

Methods: A total of 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy.

Results: 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.

Conclusions: 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.