Dave Singh discusses the use of MABAs in the treatment of COPD and the key findings of the TRILOGY and TRINITY studies.
FILMED AT THE EUROPEAN RESPIRATORY SOCIETY (ERS) INTERNATIONAL CONGRESS, SEPTEMBER 2016
The use of MABAs is a novel approach to the treatment of COPD. What are their major advantages and limitations?
00:11 – So MABAs are the combination of a beta agonist and an antimuscarinic in one molecule. So theoretically, the delivery of both active ingredients to the same site in the lung could facilitate additive and even synergistic interactions, so that when you give a mono therapy, compared to a dual therapy, you sometimes hope to get more than a simple addition, and that’s the synergistic interaction; the delivery to the same site might make this better. Now, there’s no clinical evidence to support this, but that’s the theory. There’s also simplicity in terms of giving a patient just one drug. So, traditionally, to give a beta agonist and an antimuscarinic, long acting, we would give two drugs. Giving just one drug is simple for the patient, one inhaler, and also in terms of side effects, it might limit the type of side effects that patients might potentially experience; although generally these are safe drugs and few patients experience side effects that stop them taking these medicines.
What are the most promising MABAs in clinical development?
01:26 – So there are a few MABAs in clinical development. One that’s being shown here is a MABA under clinical development with AstraZeneca. And this study shows an increase in lung function in COPD patients that is greater than some of the well-established monotherapies that we use in clinical practice, indacaterol as a monotherapy and tiotropium as a monotherapy. Now we would expect a MABA, because it has a combination of two bronchodilator mechanisms, to be better than these monotherapies, and it’s very encouraging that this was seen in this clinical trial. What we need to see now is agents like this being compared to dual bronchodilators such as indacaterol plus glycopyrronium—Ultibro or Stiolto—tiotropium plus olodaterol; and that would really tell us whether MABAs are an advance on dual bronchodilators.
Combination therapies are also an exciting area. Can you tell us a little about the TRILOGY and TRINITY studies and their key findings?
02:34 – So the TRILOGY and TRINITY studies, being presented at this congress, finally give us an evidence base for the benefits of triple therapy in COPD. So triple therapy is an inhaled steroid, plus a long-acting beta agonist, plus a long-acting antimuscarinic, all in one inhaler. So in this case, it’s the combination of beclomethasone, plus glycopyrronium, plus formoterol, given twice a day. Although triple therapy in separate inhalers is commonly used in clinical practice, actually, the evidence base for its effect on exacerbations is lacking. We know that triple therapy provides benefits in terms of lung function, and also in terms of patient-reported outcomes such as health status. But today, we have not had convincing, robust evidence regarding its effect on exacerbations. So the TRILOGY study was a comparison of the single-inhaler triple therapy against an inhaled steroid and a beta agonist. And it showed a positive benefit in terms of exacerbations, and there were also, as expected, benefits in terms of lung function and patient-reported outcomes. The TRILOGY study… The TRINITY study showed a benefit against a long-acting antimuscarinic, tiotropium alone, again in terms of all the outcomes I just mentioned. So this finally gives us an evidence base for an approach that we commonly use in clinical practice.
What other fixed dose combinations are showing promise in COPD?
04:16 – One of the fixed dose combinations that we’re using more and more is the dual bronchodilator combination: long-acting antimuscarinics plus long-acting beta agonists, all in one inhaler. Our use of these inhalers is slowly growing as we get more confidence that on the one hand, that they’re better than a long-acting bronchodilator monotherapy in terms of how patients feel, and on the other hand, we’re now getting more and more information from the SPARK study, from the FLAME study, that these dual bronchodilators positively reduce exacerbation rates. So these medicines are now becoming standard therapies for patients who do not experience exacerbations and for those who are frequent exacerbators.