Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone–Salmeterol for Chronic Obstructive Pulmonary Disease: Possible Confounding Effect of Treatment Withdrawal?

IN RESPONSE:

We thank Dr. Brown for his comments. He is correct that many patients randomly assigned into our clinical trial were already taking inhaled corticosteroids and/or LABAs at enrollment and that withdrawal effects may have played a role in influencing clinical outcomes. However, the objective of our trial was to determine whether combination treatment with tiotropium plus salmeterol or tiotropium plus fluticasone–salmeterol improved clinical outcomes in adults with moderate and severe chronic obstructive pulmonary disease. We did not intend to limit the trial only to patients who were inhaled corticosteroid–naive and LABA-naive, because this would have potentially limited the generalizability of the study findings.

We agree that an interesting additional question would be to determine whether these combinations of medications are equally effective in inhaled corticosteroid–naive and LABA-naive patients. However, recruitment for this sort of study would probably have to occur in countries where use of long-acting bronchodilator medications is not already common practice for patients with moderate and severe chronic obstructive pulmonary disease.