Authors of this first study to compare the combinations head-to-head suggest that the glycopyrrolate combination is appropriate for long-term COPD management.
In the first known head-to-head study between inhaled glycopyrrolate/ formoterol (GFF) and tiotropium/formoterol (TFF) combinations to treat patients with chronic obstructive pulmonary disease (COPD), GFF was found noninferior to TFF in improving COPD outcomes.
Reporting their findings in Contemporary Clinical Trials Communications, study authors from the SRM Institute of Science and Technology in Tamil Nadu, India, write that safety profiles and tolerability also were similar between the 2 treatments.
Inhaled bronchodilators, ie, long-acting ß-agonists (LABAs) and long-acting muscarinic antagonists (LAMA), administered alone or in combination, serve as the “backbone” for management of stable, moderate-to-severe COPD, the authors write. Past research, they observe, supports comparable safety and efficacy of the 2 LAMAs glycopyrrolate and tiotropium, the latter often considered long-term COPD management’s “gold standard” and the former recognized for more rapid onset of action and fewer side effects.
Missing from the literature, however, are studies that directly compare the 2 agents when each is administered in combination with the LABA formoterol, presenting the opportunity for the current study.
The investigators conducted a pilot prospective, open-label, parallel-arm study recruiting patients at a tertiary care hospital in the Chengalpattu district, Tamil Nadu, India. Criteria for participation included age ≥40 years with prior history of smoking and a diagnosis of moderate/severe COPD (GOLD guidelines stage 2 or 3). Enrollment also required a postbronchodilator forced expiratory volume /1s (FEV1) ≥30%/<80% of predicted as well as postbronchodilator FEV1/forced vital capacity (FVC) <0.70 at screening.
The primary study outcome was to demonstrate noninferiority between the 2 therapies in FEV1 at the end of a 12-week treatment period. The secondary study outcome was an improvement in the FEV1/FVC ratio and overall health status. Investigators used spirometry to evaluate FEV1/FVC ratio at baseline, then at weeks 4, 8, and 12. Researchers also evaluated change in health status using the St George’s Respiratory Questionnaire (SGRQ).
A total of 60 patients with moderate to severe COPD were randomized 1:1 to the GFF group (n=30) or to the TFF group (n=30). Mean age distribution between groups was 52.5 and 69.5 years, respectively; overall, 72% were men. More than half the participants in each group had a positive smoking history and the mean duration of COPD was 4.6 years. The mean post-bronchodilator FEV1 predicted percentage was 61% and the post-bronchodilator FEV1/FVC ratio was 64%. Diabetes was the most common comorbidity across the groups (40%) followed by hypertension (30%). Of the 60 original participants, 58 completed the study.
Reporting on the primary outcome the authors found that for both treatment groups there was a significant difference in average FEV1 from baseline to week 12, 1.49 ± 0.38 (GFF) and 1.38 ± 0.30 (TFF) (P<.01) and that pairwise comparison of mean FEV1 showed significant improvement among all pairs of time points (P<.01). The FEV1/FVC ratios at 12 weeks were 0.67 ± 0.09 (GFF) and 0.75 ± 0.08 (TFF) (P <.01).
Importantly the authors found that for both treatment groups, there was a significant difference in mean FEV1 and FEV1/FVC ratio values when baseline measures were compared with last follow-up (P <.01) but that no remarkable variation (p=.14) was observed in FEV1 between groups.
Following treatment, health status assessment per SGRQ demonstrated significant improvement in both groups.
Adverse drug reactions were more common among participants in the TFF arm compared with the GFF arm, according to the study, with dry mouth, constipation, and frequent urination/urinary retention reported most frequently.
In their conclusion the authors state their results demonstrate that treatment of COPD with a GFF combination was noninferior to treatment with a TFF combination for symptom improvement. They add that while safety and tolerability of the 2 combinations were comparable, GFF tolerability was somewhat better and so, they suggest, a GFF combination could be prescribed for those patients unable to tolerate TFF side effects. Further, they note that GFF could be considered for COPD long-term maintenance therapy.
The authors write that their study has limitations, including the small sample size and relatively short duration. Additionally, the open-label design of the study might have led to selection bias.
Reference: Jayanthi N, Krishnan K, Sudhir M, Girija S, et al. Comparative study on the effectiveness of glycopyrrolate/formoterol versus tiotropium/formoterol in patients with chronic obstructive pulmonary disease. Contemp Clin Trials Commun. Published online May 27, 2022. doi:10.1016/j.conctc.2022.100931