The WISDOM of ICS

I was speaking at a local educational meeting in Perth last night, the topic being COPD, as it usually is at the moment. Every month another inhaler is released, another device, another pharma company courting our prescribing pens, another combination of drugs. So when I’m asked to go out to speak to our primary cary colleagues, it’s usually about this ever expanding world of therapeutic options. The biggest current controversy has to be the apparent contradiction that ICD/LABA has been shown to reduce all cause mortality (p=0.052), reduce exacerbation rates, slow the rate of FEV1 decline, and improve quality of life, but also been shown to increase pneumonia rates in large meta-analyses, as well as individually in large studies. At the end of my little show, I’m aways asked “Double, or Triple therapy?” LABA/LAMA or LABA/LAMA/ICS?

The recent WISDOM study announced at the recent ERS, and published simultaneously in the NEJM, attempted to answer that specific question. Over 2000 patients run in on triple therapy, were randomised to stepwise withdrawal of the ICS, or continuation of triple therapy. Over a 12 month study period, the primary outcome was time to first moderate or severe exacerbation of COPD. There was no difference between either arm – withdrawal of the ICS made no difference.

Great study. But not perfect. I’d like to see a ‘real world’ study that covers the same withdrawal of steroids protocol. In this study patients were run in on triple therapy whether they needed it or not. Stopping the ICS in those patients who didn’t need it would predictably not lead to much… I’d like to take patients with COPD in the real world who have been escalated to triple therapy, and withdraw their ICS, see what happens. This was done in asthma about 10 years ago, in a primary care environment – ICS was halved in a real world population, and nothing happened. I should dig out that reference. And the study still accepted all-comers with COPD, with no attempt to separate the phenotypic groups within the heterogeny of COPD. I’d like to see the individual patient data – some patients must have deteriorated on withdrawal of ICS, because we see that it real life. Don’t we?

The inhaler landscape gets more colourful, and of varied shapes in the next few months – we’ve been waiting for the first LABA/LAMA to market, and we’ll see what is it soon enough. In my doctor-lifetime the evidence based medicine guidance has gone from LABA then LABA/ICS then LABA/LAMA/ICS; to LAMA then LAMA/LABA/ICS and no LABA/LANMA option at all; to what will soon be (I’m sure) LAMA then LAMA/LABA, then LAMA/LABA/ICS for a very select few.

Interesting times.

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