Tiotropium to Slow Lung Function Decline in Early COPD

Andrew Shorr, MD, MPH


December 12, 2017

This is Andy Shorr from Washington, DC, with a pulmonary and critical care literature update. I would like to point out the TIO COPD study by Zhou and colleagues,[1] which was published in the September 7 issue of the New England Journal of Medicine.

The TIO COPD (tiotropium in early chronic obstructive pulmonary disease) analysis was a double-blind, randomized controlled trial comparing tiotropium with placebo in patients with very early-stage COPD. This study was limited to patients with GOLD stage 1 or 2 disease.

The question was whether early use of tiotropium in a population of patients with very few symptoms, and therefore who rarely come to medical attention, actually preserves lung function and improves forced expiratory volume in 1 second (FEV1) over time compared with placebo.

We know from trials of patients with more advanced COPD that tiotropium has several positive benefits. It's a bronchodilator, it prevents COPD exacerbations, it relieves air trapping, and it improves quality of life; but in one of the largest trials of tiotropium, the UPLIFT trial,[2] it did not prevent lung function decline relative to placebo.

Perhaps that was because the drug was being used too late. That was the specific aim in terms of the analysis of the TIO COPD study. These investigators conducted this trial in China, randomly assigning approximately 840 patients over a 2-year period to either tiotropium or placebo. FEV1 served as the primary endpoint. As you would expect, the population was relatively healthy and had few symptoms. The mean FEV1 of the entire population at randomization was approximately 73% predicted. Few patients had symptoms at all.

Over the course of 2 years, the investigators found a substantial and significant between-group difference in FEV1. The difference was approximately 150 mL between the placebo and the tiotropium group, favoring tiotropium.

This translated into an improvement of approximately 22 mL in FEV1 annually in the tiotropium group. More significantly, even though this was a low-prevalence population in terms of symptoms, the addition of tiotropium was associated with fewer exacerbations and improved quality-of-life measures.

In essence, this study clearly showed that our approach to a population that pulmonologists might not see—patients with low-level symptomatology or to whom we might say that the benefits of relieving symptoms don't outweigh the hassle of taking a medication—was clearly incorrect. By adding tiotropium, these patients were able to improve lung function and quality of life.

The question remains as to whether this drug actually alters the natural history and trajectory of COPD, or whether this is just frame shifting and delaying what is going to happen inevitably. We don't know. Certainly the trial is limited in terms of generalizability because the authors report that compliance with the medication exceeded 90%, and that rarely happens in clinical practice. Perhaps the benefits were accrued because compliance was so high.

Furthermore, the study was done only in China, leaving open the question of generalizability. Nonetheless, this is an important study for pulmonologists to be aware of because we now have some data showing that with the use of a molecule that is readily available to us, we can potentially change the rate of lung function decline in our patients with very mild symptoms and early-stage COPD.


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