Leukotriene receptor antagonists: some evidence of a benefit of montelukast

In Germany, only a single drug in the class of leukotriene receptor antagonists has marketing approval: montelukast. According to the results of the studies available to date, montelukast, in combination with inhaled corticosteroids, is beneficial in mild to moderately severe asthma in adolescents and adults. However, no general additional benefit has been demonstrated for montelukast in comparison to other forms of treatment. This is the main finding of a final report published on 17 May 2006 by the Institute for Quality and Efficiency in Health Care in Cologne.

On 22 February 2005, the Federal Joint Committee ( Gemeinsamer Bundesausschuss, G-BA) commissioned IQWiG to perform an evaluation of the benefits and harms of leukotriene receptor antagonists in bronchial asthma. The indications for which montelukast had marketing approval at that time were included in the evaluation.

Combination therapy with montelukast is shown to be beneficial

For adolescents and adults with mild to moderately severe chronic asthma, combination therapy with montelukast and inhaled corticosteroids (ICS) shows advantages over ICS monotherapy at an equivalent dosage. For example, patients have 20% more asthma-free days than during monotherapy with corticosteroids. During combination therapy, exacerbations occur less often and fewer patients have asthma attacks. It may also be possible to reduce the dose of inhaled corticosteroids and thus reduce the rate of adverse effects (for example, hoarseness, reduced bone density, adrenal suppression). However, irrespective of this, the potential adverse effects of montelukast must also be considered. Concerning disease-related quality of life, no evidence has been found of an advantage of combination therapy over ICS monotherapy.

The risk of adverse effects is comparable for the two forms of therapy. However, it is not yet possible to make any conclusions on the long-term adverse effects of montelukast.

Montelukast versus salmeterol - combination therapies compared

Comparison of the efficacy of combination therapies shows that montelukast/ICS combination therapy is slightly less effective than other combined therapies (salmeterol/ICS). Overall, the combination therapy with montelukast/ICS shows less favourable results than with salmeterol/ICS. Patients have fewer symptom-free days and nights, wake up more often during the night, and the risk of exacerbations increases. Only minor differences between treatment options were shown for patients' assessments of quality of life. It is not possible to perform a conclusive comparison of the risk potentials of the two preparations on the basis of studies currently available. However, there are indications that combination therapy with montelukast is better tolerated. The number of documented hospital admissions is similar for the two forms of treatment. However, patients using montelukast/ICS therapy consult outpatient practices more often. On the basis of the available studies, no conclusions can be made on the effect on treatment satisfaction or on patients' physical capacity.

Exercise-induced asthma - no clear evidence of a benefit of montelukast

In exercise-induced asthma, in patients with an existing underlying allergic disease, acute constriction of the bronchi is triggered by physical exertion. This leads to symptoms typical of asthma, such as respiratory distress, chest tightness and coughing. There is a measurable decline in lung function. However, there is no clear threshold value for the decline in lung capacity at which patients become aware of symptoms; this was also confirmed in the scientific hearing conducted by IQWiG. A definite diagnosis of exercise-induced asthma only seems possible if both the patient's symptoms and pulmonary function are assessed. Only a few studies are available that evaluate montelukast monotherapy for exercise-induced asthma in adolescents and adults. Thus no clear evidence exists, merely indications that montelukast is beneficial in exercise-induced asthma. In one of the studies evaluated, it was found that, after using montelukast, patients had a statistically significantly longer "running time to exhaustion" and that the "sensation of effort during maximal exercise" was reduced. The safety profile of montelukast in exercise-induced asthma cannot be derived from the few available studies.

Montelukast in children - insufficient data

An exact benefit-harm assessment for children with mild to moderately severe chronic asthma or exercise-induced asthma is not possible, owing to the small amount of data available. However, there are indications that the dose of ICS can also be reduced in children using montelukast/ICS combination therapy.

Insufficient data are available to evaluate the safety profile for monotherapy or combination therapy in children.

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