Is canakinumab really a wonder drug?

This weekend’s health headlines were dominated by claims of a ‘wonder drug’ reducing heart attacks and ‘halving’ cancer.

The Telegraph
The Sun
The Independent
The Express

Now I could of course start by pointing out that every one of these reports chose to cite the relative risks (‘halves’, ‘cuts by 25%’) rather than giving us the absolute figures (how many people actually had a heart attack?) from the trial, but there are more problems than this to the story.

First up it was a large and seemingly well-conducted trial, published in a top journal (The New England Journal of Medicine), so that’s a good start. Although many journalists looked for balance though, citing the current costs of the drug as prohibitive and that the trial was sponsored by the pharmaceutical company that manufacturer it, and some mentioned that the drug increased infection risk, very few stated one thing that seems crucial to me: that the study found no evidence that the drug lowered mortality levels. On average, it apparently did not save lives.

So were the researchers getting over-excited? Well, not necessarily — the trial was actually all about determining the mechanisms of heart disease.

Lowering blood ‘cholesterol’ levels (actually, LDL levels) has long been thought to be a good way to improve our cardiovascular health. But a group of researchers think that cholesterol isn’t the whole story — that heart attacks and stroke could also be related to inflammation in the body. This is often measured by looking at the levels of markers in the blood with snappy names such as interleukin-6 and high-sensitivity C-reactive protein. Statins tend to reduce both ‘bad cholesterol’ AND these markers of inflammation, so it’s not been clear how important inflammation is in causing cardiovascular problems.

These researchers, then (sponsored by the pharmaceutical company Novartis), set out to find out, by using an anti-inflammatory drug, canakinumab, which was known to reduce inflammation without changing cholesterol levels. Would this improve cardiovascular health on its own? If it did, then inflammation is likely to be an important part of cardiovascular health. If not, then it looks as though cholesterol is the main player.

The trial was on 10,000 people who had already had a heart attack and had high levels of high-sensitivity C-reactive protein. Each got a 3-monthly injection of either a dose of canakinumab or placebo, and had their health, cholesterol and inflammation marker levels followed for 4 years.

As was hoped, the canakinumab reduced their inflammation markers and did not affect their cholesterol levels. But what happened to their health?

Outcome data from ‘Antiinflammatoy Therapy with Canakinumab for Atherosclerotic Disease’, Ridker et al., New England Journal of Medicine 2017 DOI: 10.1056/NEJMoa1707914. Participants were followed over a median of 3.7 years, meaning that the cost per participant of the drug for the length of the trial would be, on average, £140,000 (at current NICE costings).

The table above summarises some of the key findings from the trial. There was no statistically significant difference in mortality between those taking the drug and those taking placebo — so, on average there’s no evidence from this trial that it’s a life-saver.

It did significantly reduce cardiovascular events — but it significantly increased serious and fatal infections.

It didn’t significantly affect the risk of getting cancer — but it did reduce the number of people dying from it (it was already known that it blocked a pathway important for the progression of some cancers). It also had beneficial effects on arthritis, which it was already known to have.

The researchers are therefore very happy that their trial showed that the theory that inflammation was an important part of heart disease is supported by these results. But the clinical significance of their conclusions is cautious: in patients who have had a heart attack and have high levels of inflammation then an anti-inflammatory drug like this (there are others that work in similar ways) could be used alongside a cholesterol-reducing statin to help bring their risk of heart disease down. But it does come with the downside of increasing serious infection risk, and there’s no evidence from this trial that, on average, it saves lives. This is probably the most important information that a reader would want to know about the drug, and yet it was not reported by the media. Clearly it made a much more headline-grabbing story without this key information — but a misleading one.

No ‘wonder drug’ then. Perhaps no surprise either!

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