Longitudinal assessment of glucocorticoid toxicity in biologics treated severe asthma

Introduction: New biologics for severe eosinophilic asthma (SEA) significantly reduce oral corticosteroid (CS) exposure with the potential to reduce side effects from CS toxicity. We have previously reported CS toxicity using the glucocorticoid toxicity index (GTI) after 1yr biologics.(1)Aim: Longitudinal assessment of CS-toxicity reduction in SEA patients after 3yrs biologics to assess longer term CS reduction and trajectory of CS-related toxicity.Methods: 89 patients with SEA had repeat assessment of CS related toxicity 3yrs after biologic initiation using the GTI.(2) The GTI aggregate improvement score (AIS) is a bidirectional measure of total toxicity (minimal important difference (MCID) ≤-10).Results: Compared to yr1, median cumulative annual prednisolone dose continued to decrease (2518.5 v 292 mg/year at yr3, p&lt;0.001); improvement in PROMS was maintained but did not further improve at yr3.Median(IQR) AIS at 3yrs was -36 (-94, 19); 61% (54/89) met the MCID for toxicity improvement. Lack of toxicity improvement at yr1 predicted non-improvement at yr3 (30% of cohort, Figure 1). ~80% of those that met MCID at yr1 met MCID yr3.Conclusion: Toxicity assessment at 1yr predicts ongoing toxicity change; ~1/3 of patients do not have a significant toxicity reduction after 3yrs biologics questioning if biologics are introduced too late for this group.<br/

Utility of fractional exhaled nitric oxide suppression as a prediction tool for progression to biologic therapy

Rationale: The utility of fractional exhaled nitric oxide (FENO) suppression (FeNOSuppT) to identify non-adherence to inhaled corticosteroid (ICS) treatment has previously been reported, but whether it can predict clinical outcome remains unclear. Objectives: We examined the utility of FeNOSuppT in prediction of progression to biologic agents or discharge from specialist care. Methods: FeNOSuppT was measured at home using remote monitoring technology of inhaler use alongside daily FENO measurement over 7 days. Long-term clinical outcomes in terms of progression to biologic agent or discharge from specialist care were compared for non-suppressors and suppressors. Measurements and main results: Of the 162 subjects, 135 successfully completed the test with 81 (60%) positive FENO suppression tests. Subjects with a negative FeNOSuppT were more likely to proceed to biologic therapy (39 of 54 patients, 72%) compared to those with a positive FeNOSuppT (35 of 81 patients, 43%, p=0.001). In subjects with a positive FeNOSuppT, predictors of progression to biologic therapy included higher dose of maintenance steroid at initial assessment and prior intensive care unit admission. These subjects had a significant rise in FENO between post-suppression test and follow-up (median, 33 (IQR 25–55) versus 71 (IQR 24–114); p=0.009), which was not explained by altered corticosteroid dose. Conclusions: A negative FeNOSuppT correlates with progression to biologic therapy. A positive FeNOSuppT, with subsequent maintenance of “optimised” FENO, predicts a subgroup of patients in whom asthma control is preserved with adherence to high-dose ICS/long-acting β2 agonist and who can be discharged from specialist care

Glucocorticoid toxicity reduction with Mepolizumab using the glucocorticoid toxicity index

BACKGROUND: Reduction in glucocorticoid exposure is the primary benefit of new biologic treatments in severe asthma, but there is currently no evidence that reduction in glucocorticoid exposure corresponds to a proportionate reduction in associated toxicity. OBJECTIVES: To use the validated Glucocorticoid Toxicity Index (GTI) to assess change in glucocorticoid toxicity after 12 months treatment with mepolizumab, and compare toxicity change to glucocorticoid reduction and change in patient-reported outcome measures (PROMs). METHODS: A longitudinal, real-world prospective cohort of 101 consecutive patients with severe asthma commenced on mepolizumab in a specialist UK regional severe asthma clinic. GTI toxicity assessment, cumulative glucocorticoid exposure and PROMs were recorded on commencing mepolizumab (V1), and after 12 months treatment (V2). RESULTS: There was significant reduction in oral glucocorticoid exposure (V1 median 4280 mg prednisolone per year (interquartile range 3083–5475 mg) versus V2 2450 mg prednisolone per year (1243–3360 mg), p<0.001). Substantial improvements in individual toxicities were observed, but did not correlate with oral glucocorticoid reduction. Mean±sd GTI aggregate improvement score (AIS) was −35.7±57.8 with a wide range in toxicity change at individual patient level (AIS range −165 to +130); 70% (71 out of 101) had a reduction in toxicity (AIS <0); 3% (three out of 101) had no change (AIS=0); and 27% (27 out of 101) an increase in overall toxicity. 62% (62 out of 101) of patients met the AIS minimally clinically important difference of ≤−10, but AIS did not correlate with glucocorticoid reduction or change in PROMs. CONCLUSION: Mepolizumab resulted in substantial oral glucocorticoid reduction, but this did not correlate with reduction in oral glucocorticoid toxicity, which varies widely at the individual patient level. Oral glucocorticoid reduction is not a comprehensive measure of response to mepolizumab