COPD treatments: an interview with Professor Price, University of Aberdeen

Interview conducted by April Cashin-Garbutt, MA (Editor)Oct 22 2013

How many people does Chronic Obstructive Pulmonary Disease (COPD) affect and what impact does it have on their lives?

It’s a difficult number to estimate but it’s probably between four and six percent of the world’s population. So, it’s a lot of people and certainly we know that in 2000, we had about 43 million people dying of COPD.

It’s heading towards becoming the third commonest cause of death in the developed world. In fact, in some countries it already is, like the United States.

What treatments are currently available for COPD?

The first thing is that we can’t cure COPD. The problem we have with COPD is that the process itself is not treatable, certainly not once it gets to the extent that it’s advanced.

What we do know is that if we catch people very early on when they have a lot of acute inflammation, it may be that if they stop smoking at that point, they actually do see improvements.

But otherwise, smoking cessation is about slowing down the deterioration to a level that would occur if someone was not a smoker. That’s one treatment, smoking cessation.

The second is to maintain fitness and exercise, that’s very important throughout.

And then, there’s drug treatment. We like to prevent infections, so we might use vaccinations. Then, there are drugs more specific to COPD. These fall into two categories: bronchodilator therapies, which open up the lungs, and anti-inflammatory therapies, which have a limited role in specific subgroups of patients.

The main problem with somebody with COPD is that they have an obstructive airway, so they have an airway they can’t empty properly. So, by opening up their airway, they can basically empty their lungs more fully, and therefore be more active.

We also know that by opening up their airways, we reduce their chances of flare-ups of the disease - so called exacerbations - as well as helping to maintain activity.

So, bronchodilators are increasingly recognized as the mainstay of treatment and they’ve been gradually improving. We’ve had short-acting bronchodilators which often needed to be taken 4 times a day and then we’ve had better and better long-acting bronchodilators and those principally fall into two categories: long acting beta-agonists and long-acting muscarinic antagonists, which work in different and complementary ways.

We now know from more recent data that there is a substantial additive effect of putting one on top of the other, which is more than I think we expected.

Then we also have in the anti-inflammatory arena, inhaled steroids, which seem to work in people who have asthma, about fifteen or sixteen percent maybe. Also, among patients with very frequent flare-ups of disease despite bronchodilator therapy, it does seem to be that having inhaled steroids as part of their treatment regime, usually with a long-acting beta-agonist, also helps to reduce exacerbation.

There is also roflumilast, which is a PDE-4 inhibitor that has not had broad uptake yet around the world, but again seems to reduce exacerbations in people with COPD.

Those are our main therapies. There is some discussion about mucolytic agents, some discussion about theophylline, and also macrolide antibiotics. But it’s all relatively unproven.

How effective are all these therapies?

Well certainly the lives of people with COPD are quite transformed today from maybe fifteen or twenty years ago when I was first managing patients with COPD. If we can identify someone early on when they may still be working and starting to struggle with breathlessness. We can make them almost have a normal life.

I wouldn’t have dared used the term “COPD control” twenty years ago. We talked about “asthma control,” but we didn’t dare talk about “COPD control.”

However, increasingly, I think we can actually say that for many patients, particularly those with the earliest disease, we are able to make a substantial difference to their way of life, to the point where they can actually do most things they want to do.

For those with more severe disease, then it’s a matter of really helping them to best cope with it. I would say that in my referral clinic, for every ten patients I get referred with COPD, three out of those ten can be completely transformed and four or five can have a dramatically better quality of life. So, we really can make an enormous difference with treatment today.

Novartis have recently announced analyses of data for once-daily Ultibro^® Breezhaler^®. How did the investigational QVA149 compare to placebo?

What we know is that combining bronchodilators seems to give us very substantial results. What we’re actually seeing is improvements in lung function that are almost the same as if the two drugs were added together. And I think that was quite unexpected, we thought there would be more overlap of action and get maybe thirty or forty percent extra, but we’re probably getting about eighty percent extra.

So what we’re now getting is a substantial improvement in lung function which is more reliable for our patients, is more consistent, but is also bigger. So, more patients will feel the difference.

How well tolerated was the treatment?

There’s no difference taking any one of them on their own to be honest. That was interesting in the data, there’s no greater adverse effect rate.

Do these new analyses support the efficacy of dual therapy for COPD?

Very much so. It has been in the pipeline for a while, but we didn’t really have the evidence for it and we’ve actually seen evidence now in the QVA program for better bronchodilator responses.

The European Commission and Japan recently approved QVA149, nearly simultaneously, for COPD patients. What impact do you think this will have?

I think it’s going to really change the way we manage our COPD patients. We’ve had a lot of overuse of inhaled steroids in COPD. We’ve just started seeing bronchodilators becoming important first-line therapies only really in the last few years. So, classically they’ve been added onto the end, after the inhaled steroid regimes. Now, with the increased efficacy that we’re going to see from these combinations in clinical practice, they’re going to shift into being our first mainline therapy for people with COPD. Now, it may be that that gets limited in some places by cost, so it may well be that they come in as a sort of a second-line agent after one bronchodilator in some countries. In other countries, they may well become the first-line therapy for a lot of patients.

What excites you most about current research into COPD treatments?

I think really, with these new treatments we’re seeing an efficacy that’s beyond anything we ever expected before - that’s giving us a whole new positivity.

Also, the fact that so many people are starting to bring new therapies to the market is giving us an extra focus on COPD. People are also starting to look at the underlying mechanisms and looking at potential new target drugs as well… so maybe there will be some treatments that really can affect disease progression.

But even with where we’ve got to now, the ground is looking very, very, different to a few years ago and it certainly makes it very worthwhile trying to find patients who are at a much earlier stage.

What do you think the future holds for COPD treatments?

I think the future is about two things. One, it’s got to be about finding patients earlier. No matter how good our therapies are, we’re not going to be able to put the lungs back into people. So, we need to detect it in our patients earlier and to intervene earlier and more effectively. So, it may well be that that’s when we start seeing newer anti-inflammatory agents working.

However, even just the use of good bronchodilator therapy and the changes in patients’ lifestyles made earlier in disease course can make an enormous difference. And it’s as much about behavioral change as it is about therapy impacting.

The more we can catch people earlier and get them feeling better earlier, the more likely we are to make the behavioral changes that are appropriate for that too.

So, it’s a bit of a combination, that’s why I started in the beginning by talking about smoking cessation and exercise…because drugs are really about maximizing those two.

So if you can get a patient feeling well, you can change the whole trajectory of their disease without even needing to give them a new novel drug agent.

Where can readers find more information?

There’s a lot of information online. The COPD Coalition in the US has some excellent websites. The British Lung Foundation in the UK has an excellent website and there are many other national organisations.

About Professor Price

David Price is the Primary Care Respiratory Society Professor of Primary Care Respiratory Medicine at the University of Aberdeen, Scotland and Affiliate Associate Professor in the Department of General Practice at the University of Adelaide, Australia, as well as holding an honorary chair at the University of East Anglia, UK.

He completed his medical degree at the University of Cambridge in 1984, and his General Practitioner (GP) training in Norwich in 1989 where he worked as a GP principal until 2000. He now works in the Norfolk community based respiratory and allergy service.

He leads the Respiratory Effectiveness Group a not-for-profit, investigator-lead initiative which uses an international collaborative approach to explore the optimum role of real-life research in informing clinical guidelines and improving patient care.

He is a member of the executive committees for the international ARIA and EPOS guidelines groups and previous chair of the research committee of the International Primary Care Respiratory Group and chair of the Comprehensive Local Research Network in Norfolk and Suffolk.

He is extensively involved in respiratory and allergy research; his areas of special interest are ‘real-life’ effectiveness and cost-effectiveness of interventions, clinical trial design, compliance, and patient attitudes to their disease.

He has authored over 270 peer-reviewed publications since 2000 and is responsible for approximately $15 million in research and clinical development grants. He is current editor of Pragmatic and Observational research and member of the editorial board of several respiratory journals.