COPD

What does a LAMA plus LABA equal?

Wednesday, 1 Jul 2015


Respiratory expert and GOLD committee member Professor Paul Jones from the St George’s Hospital in London visited Australia this month to talk about how new dual therapy treatments are adding value to COPD patients. He also talked about why some of his patients don’t let the grandkids come for Christmas, and the importance of being able to walk a dog in the rain.

New drugs a step forward

COPD has become a much more complex and interesting disease, mainly because of the introduction of more drugs, more acronyms, and a lot more choice.

The drugs we have for COPD in the 21st century are much better than the drugs we had in the 20th century, he noted.

“I’m a little bit worried about that because there’s a tendency to say, well we’ve got good drugs so why move, why change,” Professor Jones told the audience.

We need to move on from FEV1

As a member of the GOLD Committee Professor Jones is naturally interested in COPD guidelines.

Referring to a slide of the Australian and New Zealand COPD management guidelines Professor Jones noted: “At their heart is the need to measure spirometry to make a judgment on which treatment to give a COPD patient”.

At a population level the worse the FEV1 the worse the exercise capacity, but at an individual patient level it just doesn’t work, he explained.

This is why the GOLD Committee has grouped treatment recommendations into two clusters: symptomatic benefits and improving symptoms and medium to long-term risk reduction.

Reducing symptoms

Symptomatic benefit is best achieved by long acting bronchodilators and this is recognized in the GOLD guidelines, said Professor Jones.

They state that patients, particularly GOLD group B, who have a lot of symptoms but are at a lower risk of exacerbations can use either a LABA or a LAMA.

“You may need not just one drug to get maximum symptomatic benefit you may require two long acting bronchodilators – LABA plus LAMA,” he said.

But until recently the evidence for putting two long acting bronchodilators together has been relatively weak, Professor Jones explains.

About four years ago there was a meta-analysis of key trials that showed an improvement in lung function when you added two bronchodilators, tiotropium (Spiriva™) and eformoterol in two inhalers together.

Based on this evidence many physicians, including Jones, prescribed two bronchodilators to COPD patients.

“But you can see the problem… We should not be giving COPD patients two different types of inhaler to achieve the best possible FEV1,” he told the audience.

Two in one

If you’ve got two drugs in one inhaler you need to know both are useful, said Jones.

And most dual bronchodilators on the market show an improvement in breathlessness that is better than a COPD patient would get with monotherapy.

“It means a significantly greater proportion of patients will get better with two bronchodilators compared to using one drug alone.”

“It’s not quite one plus one equals two…but it’s a pretty good additive effect,” he said.

And one of the things we know about COPD is that morning is the worst time of day for patients.

“It’s the time when they need a rapid onset of effect to get them up and going quickly, so it’s perhaps not surprising that we are seeing this worthwhile benefit in putting two bronchodilators together,” he said.

Preventing exacerbations

If you speak to any COPD patient their biggest fear is exacerbations, said Professor Jones.

For example some of his older patients in the UK will not allow their grandchildren to come visit at Christmas for fear they’ll get a chest infection.

While we can’t do much about mortality, not directly at least, we can prevent exacerbations, he said.

Treating patients to reduce exacerbations is a bit like treating hypertension to reduce the chances of a heart attack or stroke, he explained.

You don’t know which patient is going to benefit, and in the same way you don’t know which patient’s exacerbation will be prevented.

Treatment is based on the probability of benefit, he told the audience.

Fundamentally there are different approaches to the management of COPD and that is the way treatments will be used in the future, he said.

“We will see more treatments targeted largely towards symptomatic benefit and long-term risk reduction,” he said.

Safety

The organs everyone worries about with LABAs and LAMAs is the heart and there’s good reason for doing so, Professor Jones said.

LABAs can have a direct effect on the heart and LAMAs can cause tachycardia.

“And as far as we can tell there’s no increased risk putting these two long-acting bronchodilators together,” he said.

Step-up approach

The “go to” drug for symptomatic benefit in COPD has historically been a LAMA.

Following what Professor Jones terms a “step-up” approach, a COPD patient should initially be prescribed a LAMA and followed up in four weeks.

“The reason is you are giving this drug to make the patient’s COPD symptoms better and there’s only one way of knowing this and that is clinical history taking,” he said.

Quality of life means different things to different people and the disease affects each person in a unique way.

Professor Jones recalls one patient who said he could now take his dog for a walk in the rain.

“There will never be a questionnaire that has a box for walking the dog in the rain,” says Jones who developed the St George’s Respiratory Questionnaire.

He advised doctors in the audience to ask their patients if they have noticed a difference with treatment. Are they less breathless? Can they do more? Can they sleep better?

But if the patient doesn’t convince you that they’ve improved then you move them on to a LAMA/LABA fixed-dose combination” he said.

“This is what we’re all doing, it’s what I’m doing at the moment… I am an incrementalist,” he said.

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