Combining three therapies into one inhaler improves lung function and reduces exacerbations in adults with uncontrolled asthma, researchers have concluded in a paper published in The Lancet
(30 September 2019).
The paper drew together the results of two phase III trials which, for the first time, assessed the efficacy of combining three therapies — an inhaled corticosteroid (ICS), a long-acting beta-2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) — into a single inhaler.
The two randomised controlled trials — the ‘triple in asthma with uncontrolled patient on medium strength of ICS + LABA’ (TRIMARAN) and the ‘triple in asthma high strength versus ICS/LABA HS and tiotropium’ (TRIGGER) trials — recruited more than 2,500 adults with uncontrolled asthma and a history of one or more exacerbations in the previous year. The trials looked at two different strengths of the triple therapy in people with uncontrolled asthma.
In the TRIMARAN trial, 579 patients received a medium strength dose (100 micrograms) of the ICS, beclometasone dipropionate (BDP), 6 micrograms of the LABA, formoterol fumerate (FF), and 10 micrograms of the LAMA, glycopyrronium (G). The control group (576 patients) received medium dose BDP and FF.
In the TRIGGER trial, 573 patients received double the dose of BDP (200 micrograms) and the same dose of the other two medicines, FF and G. Those assigned to the control received double the dose of BDP combined with FF (576 patients) and 288 patients also received a LAMA (2.5 micrograms) in a separate inhaler.
The outcomes measured were lung function (forced expiratory volume at 26 weeks), and whether patients still experienced moderate or more severe asthma attacks at 52 weeks.
The TRIMARAN trial found that, compared with the BDP/FF control group, lung function in the BDP/FF/G triple therapy group had improved by 57mL and moderate and severe exacerbations had reduced by 15%, from an average of 2.2 exacerbations per patient per year to 1.8 exacerbations per patient per year.
In the TRIGGER trial, lung function in the BDP/FF/G group improved by 73mL, compared with the BDP/FF group, and the rate of moderate and severe exacerbations reduced by 12%, although this was not found to be statistically significant.
“Since the preventive treatment we trialled delivers three drugs via one inhaler, and given the reduction we saw in the annual rate of severe asthma attacks, we expect it will provide an attractive option helping to fulfil an unmet need for both individuals and health systems,” said Sandrine Corre, a clinical project manager at Chiesi Farmaceutici in Italy and co-author of the study.
But Anna Murphy, consultant respiratory pharmacist at University Hospitals of Leicester NHS Trust, said the key medicine in treating asthma was the ICS component of an inhaler and this should be adjusted on an individual basis to control a patient’s asthma.
“While adherence to the inhalers is likely to be better with one single triple inhaler there is no flexibility to step up/step down the ICS component of the inhaler,” she said.
“The concern is that patients will be left on an unnecessary high-dose ICS whether they are controlled well or not. It is also important to note that not all phenotypes of asthma will respond to the LAMA component and patients may not be reviewed and regimens adjusted accordingly.”
The authors noted that asthma symptoms were better controlled in all patients during the trial, including those taking the inhaler combining two medicines. They attributed this to the fact that when taking part in a trial participants are often better at adhering to their prescribed medicines and take better care of their health.