Personalising add-on treatment with inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a benefit–harm modelling study

Abstract

Background Since the benefit-harm balance of adding inhaled corticosteroids to long-acting β 2 -agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles.Methods Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderateto-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care.Findings Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54-83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40-91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per µL, patients with a BEC of 150 cells per µL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32-95% in those aged 40-79 years and 41-93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per µL or more at 52-86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%. InterpretationThe net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids.

A Prediction Scoring Model for the Effect of Withdrawal or Addition of Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease

“… 18–20 Other studies have only investigated the association between ICS response and each predictor, including blood eosinophil count, age, and history of exacerbation in the past year. 2 , 13 , 21 Compared with previous studies, our developed CASPER model could help clinicians predict the beneficial effects of ICS by comprehensively considering various characteristics of patients with COPD that can be easily measured during routine clinic visits.…”

GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: a living benefit–harm modelling study

“…The input parameters for the benefit-harm balance modelling were the relative treatment effects of GLP-1 RAs as compared to placebo, the benefit and harm outcome incidences in untreated individuals, and preference weights (relative importance) of the outcomes. 24 , 25 , 26 , 27 …”

Is Statistical Significance Alone Obsolete? – Let’s Turn to Meaningful Interpretation of Scientific and Real-world Evidence on Surgical Care

“…However, these methods have not been used to determine an M(C)ID reflecting that the benefits needed to exceed the harms. 12,13 In other words, there is a need to determine if an increase in, for example, 5% disease-free survival at 5 years (the benefit) outweighs perioperative harm reflected by, for example, a 12-point increase in CCI ® . The answer to such a question would revolutionize the field of outcome research.…”

“…Advanced methods for estimating the balance of benefits versus harms have been developed over the last 20 years, that consider all relevant evidence, also and importantly patient preferences. However, these methods have not been used to determine an M(C)ID reflecting that the benefits needed to exceed the harms 12,13 . In other words, there is a need to determine if an increase in, for example, 5% disease-free survival at 5 years (the benefit) outweighs perioperative harm reflected by, for example, a 12-point increase in CCI ® .…”