Tiotropium Withdrawal in Early-Stage Chronic Obstructive Pulmonary Disease

Background: Tiotropium improves lung function and ameliorates the annual decline in the forced expiratory volume in 1 second (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods: In this prospective cohort observational follow-up study, patients who had completed the tiotropium in early-stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified British Medical Research Council (mMRC) scores and the use of respiratory medications. Results: Of 353 patients, 262 (126 in post-placebo group and 136 in post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, both the FEV1 and forced vital capacity decreased, with no significant difference between the two groups. The frequency of acute COPD exacerbations and the mMRC scores were also similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (P<0.05 for all comparisons) at the 1-year follow-up after withdrawal, but they were not different at the next follow-up. Conclusion: Tiotropium should be continued because the lung function of the patients who had received regular treatment with tiotropium began to decline after tiotropium was withdrawn. Funding: Supported by grants from the National Key Technology Research and Development Program of the 12th and 13th National 5-Year Development Plan (2012BAI05B01 and 2016YFC1304100). Declaration of Interest: No potential conflict of interest relevant to this article was reported. Ethical Approval: The trial protocol was approved by the local institutional review board or independent ethics committee at each site according to the requirement of the Chinese guidelines for Good Clinical Practice. All participants provided written informed consent before enrollment.