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-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: Longitudinal assessment of SA patients treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement.

Methods: 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 v 0.8 mg/day (0.0,3.7) year-3, p<0.001), OCS-related toxicity continued to decline (AIS at 3yrs -36 (-94, 19), and 61% (54/89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at year-1 and year-3 (rho 0.65, p<0.001). Nearly half (49%) met the AIS MCID at both year-1 and 3, but 29% of the cohort did not meet the AIS MCID at either timepoint. 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 pre-biologics characteristics that predicted toxicity reduction.

Conclusion: After 3 years of biologic treatment, 61% of SA patients 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.