While it has been thought that cytokines (secreted signalling molecules) such as interleukin-4 or interleukin-13 have a critical role in onset and development of clinical asthma for some 20 years, confirmatory evidence has until now been lacking.
Dr Malinda Longphre, Aerovance Inc, Berkeley, California, USA and colleagues did two separate phase two clinical trials, in which patients with asthma were given pitrakinra. In study one, 12 patients were given 25mg pitrakinra by subcutaneous injection once daily, while a further twelve were given placebo. In the second study, 16 patients received either 60mg pitrakinra twice daily by nebulisation, while a further 16 were given placebo. The patients in each study inhaled allergens before and four weeks after treatment (known as ‘allergen challenge’, which induces an asthma attack).
Allergen inhalation causes an allergic reaction in the lungs which reduces their capacity to expel air. The primary endpoint for study one was maximum percentage decrease in forced expiratory volume (FEV1)** in one second over 4-10 hours after allergen challenge, whereas in study two it was average percentage decrease in FEV1 over 4-10 hours after allergen challenge. Smaller decreases in FEV1 during the asthma attack for the pitrakinra group versus placebo would mean that the allergic response had been decreased by pitrakinra.
The researchers found that in study one, the maximum percentage decrease in FEV1 was 17.1% in the pitrakinra group and 23.1% in the placebo group – a relative difference of 26%. In study two, the average percentage decrease in FEV1 was 4.4% in the pitrakinra group compared with 15.9% in the placebo group – (more than 3 and half times less in the pitrakinra group).
The authors conclude: “The effects of pitrakinra on late phase asthmatic response are promising when compared with similar studies with other successful anti-inflammatory asthma therapies…..whether the effect is due to inhibition of interleukin-13 alone, or both interleukin-13 an interleukin-4, is not yet known. Future studies of this drug, as well as molecules that specifically inhibit interleukin-13, in asthmatic individuals of all levels of severity over longer periods of time are clearly warranted.”
In an accompanying Comment, Dr Patrick Holt and Dr Peter Sly, Telethon Institute for Child Health Research, University of Western Australia, Subiaco, Western Australia, Australia, say: “These latest findings with pitrakinra are exciting and novel, and will breathe new life into the debate surrounding the role of the Th2-cytokine cascade in asthma pathogenesis and how best to design drugs to attenuate their effects.”
Tony Kirby | alfa
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