In order to widen the narrowed airways in patients with chronic obstructive pulmonary disease (COPD), tiotropium bromide (tiotropium in brief) is one of the drugs available that can be prescribed for inhalation. The German Institute for Quality and Efficiency in Health Care (IQWiG) has examined whether tiotropium offers a perceptible advantage to patients compared to a dummy medication (placebo) and to other COPD drugs. In addition, the two currently marketed types of inhaler (HandiHaler and Respimat) for tiotropium (trade name: Spiriva-) were compared.
According to the IQWiG report, there is proof that tiotropium offers patients with COPD advantages compared to placebo: they suffer fewer acute worsenings of their condition (exacerbations), they need to be hospitalized for this reason less often, and their quality of life is better. There are indications of a benefit in terms of less severe symptoms and complaints, e.g. breathing problems. In relation to the ability to carry out everyday practical activities, there is also a hint of a benefit of tiotropium.
An added benefit is also proven in comparison with the drugs salmeterol, formeterol, indacaterol and ipratropium: fewer exacerbations and related hospitalizations occurred under treatment with tiotropium. Compared to indacaterol there is, however, also a hint of a lesser benefit of tiotropium with regard to the COPD symptoms and quality of life.
Effects for COPD patients are the focus of interest
Tiotropium is a drug known as an "anticholinergic" that is used for the treatment of COPD, in which the airways are permanently narrowed and the lungs are damaged. The disease is characterized by chronic cough, increased sputum and shortness of breath on exercise. About 1 in 10 to 20 adults aged over 40 has COPD. Thus, the disease is much more common than asthma. Three-quarters of patients are men.
Because of the strong association with smoking, COPD is also commonly known as "smokers' cough".
The outcome measures of this benefit assessment, in addition to symptoms, acute exacerbations and the resulting need for hospitalization, included mortality (deaths), health-related quality of life and side effects.
Comparison with placebo shows advantages for patients
In its worldwide search for clinical trials and systematic reviews, the Institute found a total of 27 relevant studies.
The 21 studies comparing tiotropium with a placebo produced proof of a benefit in relation to exacerbations and hospitalizations due to exacerbations. Also proven is the benefit in respect of quality of life, because the study participants using tiotropium suffered less from breathing problems and their physical health was better than in the control group. In both cases, the proof applied to both types of inhaler.
An indication of a benefit from tiotropium (again for both inhalers) could be demonstrated in relation to symptoms. For the HandiHaler, there is also a corresponding indication in terms of the mortality rate of ex-smokers.
IQWiG found a hint of a benefit for everyday practical activities. Here, the final report differed from the preliminary report because of additional data from a new study that IQWiG identified during the routine supplementary search.
Tiotropium compared to other COPD drugs
In 10 studies tiotropium was compared with other drugs, namely with ipratropium, with the combination of salmeterol and fluticasone and with the group of drugs known as "LABA". The conjoint analysis of the long-acting beta-2 sympathomimetics salmeterol, formeterol and indacaterol in the LABA group takes account of arguments from the commenting procedure on the preliminary report. As a consequence, advantages of tiotropium that are shown with one of the LABA drugs, apply to the entire group. The results of these 10 studies in general apply only to the HandiHaler inhaler, because only placebo-controlled studies were available for the Respimat.
Added benefit compared to LABA and ipratropium
Unlike in the preliminary report, the comparison with ipratropium showed not only proof of a benefit of tiotropium in relation to exacerbations, but - because of new analyses submitted during the commenting procedure - also an indication of a benefit in relation to COPD symptoms. In contrast to tiotropium and LABA, ipratropium is short-acting and must therefore be taken more often.
Proof of an added benefit of tiotropium over the LABA drug class could be demonstrated in relation to exacerbations and resulting hospitalizations.
However, compared to indacaterol there were also two hints of a lesser benefit of tiotropium, namely in respect of symptoms and quality of life. Although indacaterol belongs to the jointly considered LABA drug class, the study results vary a great deal in respect of these patient-relevant outcomes. The drugs were therefore assessed separately for the two above-named outcomes.
The comparison of tiotropium with the combination of salmeterol and fluticasone produced no differences for the patients with COPD.
No differences for other outcomes and as add-on medication