Tiotropium/olodaterol in COPD: Disadvantages in some patients, advantages in others

November 20, 2015

The fixed-dose combination of tiotropium and olodaterol (trade name: Spiolto Respimat) has been approved since July 2015 for maintenance treatment in adults with chronic obstructive pulmonary disease (COPD). The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether this drug combination offers an added benefit over the appropriate comparator therapy.

According to the findings, there were no statistically significant differences between the treatment groups for the totality of adults with moderate COPD symptoms (severity grade II) and higher severity grades (III-IV) and fewer than two flare-ups (exacerbations) per year. Indications of a minor added benefit could only be derived for women in these COPD groups who inhaled the fixed-dose combination.

In adults with higher severity grades (< III) and at least two flare-ups per year, even disadvantages occurred, which resulted in proof of lesser benefit.

Comparator therapy depends on severity and frequency of exacerbations

The Federal Joint Committee (G-BA) specified different appropriate comparator therapies depending on the severity of the disease: From a moderate COPD severity grade (stage II), the new drug combination was to be compared with a long-acting beta-2 sympathomimetic (LABA, e.g. formoterol, salmeterol) and/or tiotropium (research question 1). From severity grade III and at least two flare-ups (exacerbations) per year, the patients in the comparator arm were to receive an additional inhaled corticosteroid (ICS) (research question 2).

Assessment based on subpopulations

The manufacturer presented data from two approval studies (TONADO 1 and 2) with patients diagnosed with moderate to severe COPD. In contrast to the G-BA's specifications, all patients included in these studies could continue ongoing treatment with an ICS. Hence for both research questions, the assessment was based on subpopulations treated in compliance with the G-BA specifications.

The average age of the patients in the subpopulations was 60 years, and the majority were men: depending on the subpopulation, there were twice to four times as many men as women.

Analyses on longest possible treatment duration

For maintenance treatment in a chronic disease, such as tiotropium/olodaterol, analyses over a longer period of time are more suitable for drawing conclusions on long-term effects. Analyses after 52 weeks were therefore used for all outcomes in the present assessment. The manufacturer, in contrast, had also considered analyses after week 24 in some outcomes.

Advantages only for women with rare flare-ups

For most adults in the subpopulation with severity grade II or severity grade III and IV with fewer than two exacerbations per year, no relevant differences between the treatment groups were shown, or data were lacking, for most outcomes (e.g. COPD symptoms, exacerbations, quality of life, severe side effects).

Positive effects regarding health-related quality of life and COPD symptoms (shortage of breath) under the fixed-dose combination were only shown for women in this subpopulation. In each case, an indication of minor added benefit of tiotropium/olodaterol in comparison with tiotropium can be derived from this. The data provided neither positive nor negative effects for men.

Disadvantages in severe/very severe COPD with several exacerbations

No relevant differences between the treatment groups occurred or data were lacking also for the second research question (adults with severity grade higher than III and at least two exacerbations per year) in most outcomes.

However, severe exacerbations were more frequent in patients who had inhaled the fixed-dose combination. This resulted in proof of lesser benefit of tiotropium/olodaterol plus ICS in comparison with tiotropium plus ICS.

G-BA decides on the extent of added benefit

This dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website » http://www.gesundheitsinformation.de, published by IQWiG, provides easily understandable German-language information.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on » http://www.informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to » info@iqwig.de.

Institute for Quality and Efficiency in Health Care

Related COPD Articles from Brightsurf:

Promising therapeutic approach against COPD
Chronic obstructive pulmonary disease (COPD) is one of the most common and deadliest diseases worldwide.

COPD underdiagnosed in older adults, but can be managed
''Recognizing and Treating COPD in Older Adults'' the latest issue of the What's Hot newsletter from The Gerontological Society of America, addresses what is known about the prevalence, incidence, and impact of chronic obstructive pulmonary disease (COPD) in older adults.

Undersized airways may explain why nonsmokers get COPD
A mismatch between airway and lung size may explain why some nonsmokers get COPD and some heavy smokers do not, according to a new study from Columbia University Irving Medical Center.

Is pulmonary rehab after hospitalization for COPD associated with better survival?
Claims data for nearly 200,000 Medicare patients were used to examine the association between starting pulmonary rehabilitation within 90 days of being hospitalized for chronic obstructive pulmonary disease (COPD) and survival after one year.

COPD and smoking associated with higher COVID-19 mortality
Current smokers and people with chronic obstructive pulmonary disease (COPD) have an increased risk of severe complications and higher mortality with COVID-19 infection, according to a new study published May 11, 2020 in the open-access journal PLOS ONE by Jaber Alqahtani of University College London, UK, and colleagues.

COPD as a lung stem cell disease
Two internationally renowned stem cell researchers at the University of Houston have found an abundance of abnormal stem cells in the lungs of patients who suffer from Chronic Obstructive Pulmonary Disease (COPD), a leading cause of death worldwide.

New hope for COPD patients possible with in-home device
In a new paper published Feb. 4 in JAMA, Mayo Clinic researchers describe the benefits of in-home noninvasive ventilation therapy, which includes a type referred to as bilevel positive airway pressure, or BiPAP -- for many patients with chronic obstructive pulmonary disease (COPD).

COPD appears to cause more severe symptoms in women
Women who develop COPD report smoking fewer cigarettes than men; and yet, women experience greater breathing impairments, are subjected to more acute exacerbations of symptoms and report lower quality of life than men with the disease, according to research presented at ATS 2019.

African-Americans with COPD appear less likely to use pulmonary rehab
African-American patients with chronic obstructive pulmonary disease, or COPD, are less likely to participate in pulmonary rehabilitation programs than white patients, even when there are programs nearby.

COPD and type 2 diabetes
COPD and type 2 diabetes are two highly prevalent global health conditions associated with high mortality and morbidity.

Read More: COPD News and COPD Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.