Evaluating a Cox marginal structural model to assess the comparative effectiveness of inhaled corticosteroids versus no inhaled corticosteroid treatment in chronic obstructive pulmonary disease

Purpose: To evaluate the potential of a Cox marginal structural model (MSM) to estimate the time-varying causal inference of a known clinical trial association where the effectiveness of inhaled corticosteroid- (ICS-) versus non-ICS-containing treatments has been compared in patients with chronic obstructive pulmonary disease (COPD).

Methods: This retrospective study from 2006-2016 used linked data from Clinical Practice Research Datalink-GOLD, Hospital Episode Statistics, and Office for National Statistics mortality. A Cox MSM, incorporating a new-user design, was deemed capable of replicating a clinical trial-like pathway. Repeated outcomes for exacerbation events and stabilized weights were used to include time-varying and fixed covariate exposures.

Results: Of 45,958 patients, 55% were male; 52% had moderate COPD. ICS-treated patients had a higher incidence of comorbid asthma than non-ICS-treated patients. Adjusted hazard risk ratios for any exacerbation event: ICS and/or long-acting β₂-agonist (LABA) versus long-acting muscarinic antagonist (LAMA), 1.07 (95% confidence interval 1.04-1.10); ICS/LABA versus LABA and/or LAMA, 1.05 (1.00-1.10); ICS and/or LABA and/or LAMA versus LAMA, 1.04 (1.01-1.06); ICS and/or LABA and/or LAMA versus LABA and/or LAMA 1.02 (0.97-1.07).

Conclusions: The Cox MSM was not able to fully demonstrate results consistent with the previously established benefits of ICS-containing treatments seen in clinical trials. Future studies should continue to investigate causal inference methods and their capability to estimate the long-term outcomes of treatment in COPD.