LaForce C, et al. - In a prespecified safety analysis of the TONADO studies, researchers determined the long-term safety profile of tiotropium/olodaterol in patients with renal impairment as tiotropium is predominantly excreted by the kidneys. Renal impairment was present in over half the patients enrolled in the TONADO studies, with an elevated level of pre-existing cardiovascular comorbidity. They found that, regardless of the level of renal impairment, tiotropium/olodaterol demonstrated safety and tolerability which were comparable to the monocomponents.

Methods

• In these 2 replicate, randomized, double-blind, parallel-group, 52-week Phase 3 studies, tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat) was tested in patients with moderate-to-very severe COPD.
• The definitions of renal impairment were mild (creatinine clearance [CLcr] 60–89 mL/min), moderate (CLcr 30–59 mL/min) or severe (CLcr 15–29 mL/min).
• From both studies, adverse events (AEs) were pooled.

Results

• This study included 3,041 patients, and 1,333 (43.8%), 404 (13.3%) and 5 (0.2%) had mild, moderate, and severe renal impairment, respectively; these were distributed equally between treatment groups.
• A history of cardiac disorder was present in almost one-quarter of all treated patients (23.4%); 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes.
• Researchers noted the occurrence of AEs with olodaterol, tiotropium, and tiotropium/olodaterol in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively.
• They reported no significant effect of renal impairment on the proportion of patients with an AE, and found that tiotropium/olodaterol vs the monocomponents did not differ.
• Findings demonstrated no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment.