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People with severe chronic obstructive pulmonary disease (COPD) often have persistent dyspnea or exacerbations despite the use of a single controller inhaler. (Controller inhalers for COPD most often include combination inhaled corticosteroid/long-acting beta agonists like Advair, Dulera and Symbicort [ICS/LABAs] and the long-acting anticholinergic agent Spiriva/tiotropium). These patients often take both a combination ICS/LABA and Spiriva, so-called "triple therapy". There's some limited evidence to suggest triple therapy (adding tiotropium) results in better outcomes than inhaled steroids + LABAs alone.
Once any medication gets started, it can be hard to stop. Besides the actual benefits of the medication, perceived safety concerns and psychological dependence or fear of cessation have to be considered. Unlike in asthma, guidelines for COPD treatment don't address "stepping down" to the lowest dose of medications.
If you're making a new combined once-daily long-acting controller inhaler containing tiotropium and the long-acting beta agonist olodaterol, like Boehringer Ingelheim, that's a problem. Since your new drug doesn't contain any corticosteroid -- and inhaled corticosteroids (ICS) prevent COPD exacerbations -- how will you convince millions of COPD patients around the world treated with ICS, and their doctors, to switch to your steroid-free drug? Not to mention there were all those safety concerns about LABA use without simultaneous ICS use (which was only ever a concern in asthma, not COPD, but that's a distinction many people forget)?
Well, a big article in the New England Journal can't hurt your cause.
Authors randomized 2,485 patients taking triple therapy (salmeterol, fluticasone, and tiotropium, i.e., Advair+Spiriva) to either continue all three agents, or switch to taking a LABA + tiotropium (without inhaled corticosteroids) for 9 months. Wait a minute, those are the same two drug classes in Boehringer's forthcoming new COPD drug! Quelle coincidence!!
The trial, conducted at what must have been enormous expense (12 months, 200 centers, 23 countries) was a success: it showed the patients stopping inhaled corticosteroids did not have a higher rate of COPD exacerbations than those continuing triple therapy (hazard ratio of 1.05 in those stopping ICS). However, there was a small reduction in lung function (about 40 mL lower FEV1) in those stopping ICS, compared to those continuing triple therapy.
An associated editorial clothes the trial in noble purposes, suggesting (with an irony that's apparently unintentional) lower health care costs and reduced risks of pneumonia could result by "stepping down" ICS. These cheers don't quite ring true (payers negotiate down the prices for combination agents, often below that of the single agents; "stepped down" patients would still pay a copay, which may be the same; some believe ICS reduce the mortality from pneumonia while minutely increasing its incidence). Nowhere is the apparent strategic goal of the multi-million dollar trial alluded to.
I'm sure Boehringer is a great company, but it's not a charity. This study's design and intended effect seems to have been to ease anxiety among physicians and patients about switching COPD patients from ICS/LABAs to Boehringer's forthcoming steroid-free once-daily combination agent (retail price yet to be announced) -- and to make that new product more attractive compared to once-daily steroid-containing inhalers (Breo Ellipta, et al) being marketed by the competition.
And in that, I must admit they have succeeded. Well played, folks.