Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - European Respiratory Society (ERS) Annual Congress 2013

Barcelona, Spain / September 7-11, 2013

Barcelona - Based on a survey presented as a latebreaking presentation at the 2013 ERS, almost all specialists in chronic obstructive pulmonary disease (COPD) are aware of the GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines, but only about half report close adherence (Aisanov et al. ERS 2013 Abstract 927). The reason appears to be that specialists prefer the individualization of care undertaken to improve quality of life even when this requires deviation from the guidelines. The justification for keeping a focus on quality of life, based on survey responses, is skepticism among specialists regarding the ability of treatment to halt disease progression beyond that provided by tight symptom control.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

The GOLD-based goals of treatment are relief of symptoms, improved exercise tolerance, and improved health status (www.goldcopd.org). The guideline goals also include prevention of disease progression, but due to the frequency with which COPD is accompanied by co-morbidities as well as the limited evidence that treatment other than smoking cessation and tight control of symptoms changes COPD outcome, experts contend that individualization of therapy is essential.

Individualization of Treatment

«There is a great deal of variability in COPD even among those with similar degrees of airflow limitation, so we have to think of treatment within the context of the patient in front of us,» reported Dr. Bart Celli, MD, Division of Pulmonary and Critical Care Medicine, Harvard Medical School, Boston.

As a co-author of a study that demonstrated patient population characteristics, such as baseline FEV₁, influence efficacy of bronchodilators in placebo-controlled trials (Decramer et al. ERS 2013, Abstract 749), Dr. Celli cited these data, as well as the ECLIPSE trial (Vestbo et al. N Engl J Med 2011;365:1184-92), to support individualization of therapy on the basis of variability in lung function decline. In the data he presented with Dr. Marc Decramer, University of Leuven, Belgium, the goal was to identify factors that influenced disease progression in the previously published UPLIFT trial (Tashkin et al. N Engl J Med 2008;359:1543-1554). Significant variability in exacerbation rates was traced to such baseline characteristics as current smoking, concomitant medications, and FEV₁.

«Individual patients have individual symptoms and individual problems,» Dr. Celli reported. Although data from large trials, such as UPLIFT, which demonstrated benefit from the long-acting muscarinic antagonist (LAMA) tiotropium, have helped guide therapeutic choices, treatment of the individual patient should focus on controlling specific symptoms, such as low exercise tolerance, nighttime dyspnea, or cough.

The latebreaking international survey of physicians indicates other specialists agreed. In the survey of more than 1,300 physicians, 25% were specialists and 75% were primary care providers. Although awareness of the guidelines was higher among specialists (93% vs. 58%), application of the guidelines among those who were aware was somewhat lower in the specialist group (51% vs. 61%). Conversely, specialists were more likely to manage COPD patients according to the patient’s own perception of symptoms through self assessments (81% vs. 67%), such as the COPD Assessment Test (CAT).

«Knowledge of the GOLD guidelines is high among specialists, though these results suggest that the recommendations are not applied rigorously in routine care,» reported Dr. Zaurbek Aisanov, Pulmonology Research Institute, Moscow, Russia. One reason for a focus on quality of life may be that 46% of the survey participants do not believe that available treatments reduce COPD mortality.

GOLD guidelines recommend long-acting bronchodilators as the preferred first-line therapy without distinguishing between LAMA and long-acting beta agonists (LABA). According to Dr. Celli, many specialists initiate therapy with a LAMA on the basis of efficacy trials, particularly UPLIFT, which have associated the LAMA tiotropium with improvements in quality of life.

Initiating Therapy

Tiotropium has now been joined in many countries by glycopyrronium, for which the Phase III GLOW trial was published previously (D’Uzo et al. Respir Res 2011;12:156), and aclidinium, for which Phase III data were presented at the 2013 ERS. In the GLOW trial, glycopyrronium was safe and well tolerated and demonstrated a highly significant advantage over placebo for the primary end point of improvement in FEV₁ at the end of 12 weeks. At ERS 2013, indirect comparative data for glycopyrronium and tiotropium were derived from a trial designed to evaluate a once-daily combination of glycopyrronium and the LABA indacaterol (Wedzicha et al. ERS 2013, Abstract 180). In that study, randomization arms included once-daily glycopyrronium and once-daily tiotropium. As monotherapy, these agents were similarly effective for reducing exacerbations and improving lung function.

The newest LAMA to complete Phase III studies is aclidinium, which is administered twice-daily with the intention of improving 24-hour symptom control. In data presented at the ERS, 414 COPD patients were randomized to 400 μg of this agent twice daily or placebo (Beier et al. ERS 2013, Abstract 184). In a third, comparator study arm, patients received 18 μg once daily of tiotropium. At the end of 6 weeks, aclidinium provided greater reductions from baseline than placebo in the most common COPD symptoms, but it also appeared to perform better relative to the comparator tiotropium for some endpoints. Although this was not designed as a head-to-head comparison, tiotropium, unlike aclidinium, did not significantly reduce night time severity and reduction in activity limitation (due to symptoms) from baseline.

«The greater symptom improvements for aclidinium relative to tiotropium may be the result of the twice-daily dosing, which allows a boost in the exposure to active drug in the evening hours, but it may also be related to differences in the inhaler,» reported Dr. Jutta Beier, Insaf Respiratory Research Institute, Wiesbaden, Germany, who also presented a second study that included an inquiry about patient satisfaction with these devices (Beier et al. ERS 2013, Abstract 185).

According to this second analysis, patients preferred the device that delivered aclidinium over the one that delivered tiotropium. While this preference was subjective, Dr. Beier quoted a recently published study that found critical errors to be lower with the proprietary device developed to deliver aclidinium vs. that most commonly used to deliver tiotropium (van der Palen et al. Expert Opin Drug Deliv 2013;10:1171-8).

Specific Symptoms

The evidence that LAMA agents may differ for specific types of COPD symptoms, such as nighttime and early morning dyspnea, is relevant to individualization of therapy. Although not all COPD patients have significant nighttime symptoms, twice-daily dosing could distinguish between LAMA therapies for those who do, according to Dr. Beier in presenting the Phase III data.

More comparative data for the enlarging LAMA class of bronchodilators are needed, particularly in evaluating relative effect beyond changes in FEV₁ and other conventional measures of lung function. Potential differences in the relative effects against specific symptoms, such as cough or exercise endurance, may make one agent more attractive than another in a specific individual. In general, LAMAs have been well tolerated, but differences in the relative risk of cholinergic side effects may also distinguish these agents.

«COPD patients must be treated individually,» maintained Dr. Celli, referring back to the observational ECLIPSE study, which assessed FEV₁ change over three years in 2,163 COPD patients maintained on a bronchodilator. In that study and indicative of individual variability in disease progression, the mean FEV₁ decline was 33 mL per year, but the standard deviation was 59 mL per year. While 38% had an annual decline of 40 mL or more, 31% had a decline of no more than 20 mL per year. Not surprisingly, current smoking was a predictor of disease progression, but chronic bronchitis was not, and bronchodilator reversibility at baseline predicted slowly advancing disease.

Conclusion

COPD patients vary widely in the types of symptoms and the speed of lung function decline. This variation encourages individualization of therapy, which appears to be widely practiced by COPD specialists. While GOLD guidelines identify an appropriate sequence of treatments, attention to specific symptoms may be important for selecting among first-line bronchodilators and other therapies as the disease progresses.