1. Conclusions Purpose Results Results Discussion Methods Conclusions
Are three little piglets all the same?
A nine month prospective cohort crossover study with tiotropium, aclidinium and glycopyrrhonium
With patients acting as their own controls
Stefan Rustscheff, MD , Anna Wingerup,MD
Department of Internal Medicine and Värnamo Hospital Community Health Centre
Värnamo General Hospital
SWEDEN
Purpose
Results
Results
Discussion
We wanted to examine if patients with stable, severe COPD would benefit from a trial of all available long acting muscarinic antagonists currently marketed in Sweden. We chose to have tiotropium as the gold standard and measured differences in exacerbations, FEV1, Quality of Life, dyspnea and subjective patient preferences.
Two patients failed to activate the Eklira device during treatment in spite of being able to operate it on inclusion due to low PIF capacity. All other patients managed to show that they could use all inhalers successfully.
Both treatment groups experienced exacerbations compared to the run-in phase. 32% in the aclidinium group and 26 % in the glycopyrrhonium group. The difference towards tiotropium was significant using the Chi square test but not between the groups. (p=0.005)
A 10-point Borg Quality of life index scale was used and data showed that 6% of patients in the aclidinium group and 19% in the glycopyrrhonium group experienced a loss of Quality of life of 2 or more points. On the other hand, 9% and 10 % in the respective groups experienced an improvement of Quality of life of 2 or more points.
The total sum difference in Quality of life was +3 % in the aclidinium group and -9% in the glycopyrrhonium group. Neither were statistically significant using the Chi square test.
A 10-point Borg Dyspnea scale was used and dyspnea worsened in 12% in the aclidinium group and 23% in the glycopyrrhonium group.
Dyspnea improved in 24% in the aclidinium group and 10 % in the glycopyrrhonium group.
The total sum difference in Dyspnea was +14% in the aclidinium group and -13% in the glycopyrrhonium group.
The difference to tiotropium and between the two groups were statistically significant using the Chi square test with goodness of fit. (p=0.005)
In a homogenous cohort of severely ill patients with COPD, all with a maximum FEV1 of 1.5 l and a mean FEV1 of 0.8 l we found that patients had a wish to try other inhalers on the market, and that a large subset of patients wanted to continue with that inhaler, given the choice to do so.
A fairly small subset of patients improved their FEV1 significantly, but those who did wanted to change their tiotropium spray to the new product. Just as many additional patients wanted to switch to a new inhaler from tiotropium, in spite of not being improved in either Quality of life, Dyspnea, FEV1 or exacerbations. The study obviously started with exacerbation free subjects, and receipt of an exacerbation invariably made the patients want to go back to their original inhaler.
Out of 38 patients who completed all the legs of the study, 19 chose to return to tiotropium.
11 patients out of 31 preferred to retain glycopyrrhonium and 8 out of 34 patients preferred to remain on aclidinium.
The FEV1 value was predictive of patient preferences in that all patients chose an inhaler giving them FEV1 values significantly higher than their original therapy. However, many patients with no difference in FEV1 also chose to switch to another inhaler and FEV1 loss did not necessarily mean reinstation of the original therapy with tiotropium.
FEV1 gain compared to tiotropium was not seen for any group as a whole, although 4 patients each, 12%, noted a significant FEV1 gain of 0.2 l in both the aclidinium group and the glycopyrrhonium group, while 8 patients in each group lost 0.2 l in FEV1.
All in all, the participants in the aclidinium group had significant improvement in dyspnea compared to tiotropium and glycopyrrhonium. Both groups experienced more exacerbations than at baseline treatment. There were no significant differences in FEV1 for the groups as a whole, but individuals experiencing a significant improvement in FEV1 chose to switch inhalation devices to the one giving FEV1 improvement when allowed to do so.
50% of the total participants chose another drug than tiotropium at the end of the study period, in spite of only 25% experiencing any improvement in FEV1 compared to tiotropium and in spite of 50% actually experiencing exacerbations during the study period.
FEV1 gain was strongly positively predictive for change and exacerbations were strongly negatively predictive for change.
Methods
A prospective open cohort crossover study, with patients acting as their own controls. The cohort consisted of all patients cared for by the Section for Pulmonary diseases, Värnamo General Hospital, with COPD grade 4 as defined by the modified GOLD criteria of 2014, with stable disease, no exacerbations during a retrospective run-in phase of three months and on inhaled tiotropium 2.5 mg, 2 doses daily, as their muscarinic antagonist for at least one year.
Quality of Life, perceived dyspnea severity and spirometry values were measured. Inhalation techniques were checked, and the patients were then taught the Eklira Genuair (aclidinium bromide 322 microgram bd) and the Seebri breezhaler (glycopyrrhonium 44 microgram once daily).
The cohort characteristics were as follows: all patients had smoked at least 20 pack years. None had a concurrent diagnosis of asthma or a reversibility over 13 % in their spirometry values. Exclusion criteria were other interstitial diseases, malignant disease, cardiac failure, current smoking, inability to use any of the inhalation devices or unwillingness to participate in the study. All patients were tested on their ability to operate the Eklira device which demands the greatest inspiratory effort, 48 l/min in PIF values. Baseline medication consisted of Tiotropium, salmeterol/fluticasone 50/250 mcg or budesonide formoterol 160/4.5 mcg and theophylline 200 mg bd.
Conclusions
Conclusions
A significant rise in FEV1 will make a patient previously well controlled on a gold standard treatment want to change therapy. Subjective factors play just as large a role of patient behaviour since twice as many patent chose another inhaler when given the opportunity. Switching to aclidinium provided dyspnea relief in a large number of subjects, which was statistically significant compared to a worsening in dyspnea perceived in a subset of patients on glycopyrrhonium. Nevertheless 29 % wanted to continue with glycopyrrhonium and only 21 % with aclidinium showing that the will of a patient indeed walks in mysterious ways. Experiencing an exacerbation on a new drug makes a patient want to go back to a tried and tested one. Given that 50% of patients altogether wanted to make a change from tiotropium shows that this drug remains the Gold Standard, but that gold may be perceived to be lead by some. 1.
-facile est inventis addere-