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Are the crippling side effects of new cancer ‘miracle drugs’ worth the risk?

Surviving cancer against expectations can give patients new life. But what if the drugs that save them then leave them with another painful, incurable disease?

That’s a reality that cancer specialists and patients around the world face as more and more people benefit from immunotherapy – groundbreaking new drugs that use the body’s immune system to attack cancer.

In many cases these diseases cannot be treated further.

The first cancer immunotherapy drugs – usually given as weekly or bi-weekly infusions – were licensed in the UK in 2011 for advanced melanoma, the most serious form of skin cancer that has spread to other organs. And they have been hailed as game changers against these tumors.

The treatment costs about £ 100,000 per patient per year and has potentially crippling side effects. A doctor and patient (photo file)

The treatment costs about £ 100,000 per patient per year and has potentially crippling side effects. A doctor and patient (photo file)

For example, in the 1990s, patients with advanced melanoma survived an average of only six months. Today, the average survival rate is three to five years, and in some cases longer, thanks to immunotherapy drugs such as ipilimumab (brand name Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo). These all work by strengthening the body’s defenses to destroy cancer cells.

Patients with otherwise untreatable tumors of the lung, kidneys, head and bladder now also benefit from immunotherapy, which costs approximately £ 100,000 per patient per year.

But as the prescription of the drugs grows wider, studies suggest that thousands of patients are paying a price for the success of the treatment. Research shows that about one in ten patients who receive cancer immunotherapy will experience potentially crippling rheumatoid arthritis as a side effect.

Rheumatoid arthritis, an autoimmune disease in which the immune system mistakenly attacks the cells in the joints, affects about 350,000 people in the UK and causes painful, inflamed joints and extreme fatigue.

One in ten patients who receive cancer immunotherapy develops rheumatoid arthritis

One in ten patients who receive cancer immunotherapy develops rheumatoid arthritis

One in ten patients who receive cancer immunotherapy develops rheumatoid arthritis

The first report of such side effects was in 2018, when doctors at the Johns Hopkins Arthritis Center in Baltimore, USA, examined 30 patients who developed joint problems after taking the immunotherapy drugs ipilimumab, pembrolizumab and nivolumab. All had developed pain and inflammation in both knees within weeks of starting immunotherapy. Those who received two immunotherapy medications at the same time – a common practice to increase their effectiveness – also had inflamed lungs and intestines, the journal Seminars in Arthritis and Rheumatism reported.

Most improved after taking large doses of steroids to dampen inflammation, but a third needed stronger drugs called TNF inhibitors (which block a protein called tumor necrosis factor alpha that promotes inflammation).

While highly effective, these medications can also have side effects ranging from chronic fever and bruising to numbness and blurred vision. And while they can relieve symptoms, they are not a cure for rheumatoid arthritis.

So how can drugs designed to destroy cancer end up causing problems with our joints?

Rheumatoid arthritis is triggered when the immune system goes haywire and begins to destroy healthy joints. Scientists think the cancer drugs can put the immune system into self-destruct mode in some patients.

These drugs work by turning off specific proteins found on the surface of cells of the immune system that prevent them from attacking the body’s healthy tissues.

Cancer cells use this built-in protection system to slip past the body’s defenses. But once these proteins are inactivated by the immunotherapy drugs, the immune system is free to hunt down and destroy tumor cells.

In some cases, however, this also appears to lead to the destruction of healthy cells, such as those in the bones and joints.

And it’s not just rheumatoid arthritis that’s the problem. Other research shows that about 1 percent of patients taking the drugs develop type 1 diabetes – another common autoimmune disease, which occurs when immune cells attack the pancreas, causing patients to rely on daily insulin injections to control blood sugar. hold.

That’s the magnitude of the problem that earlier this year the European League Against Rheumatism – an agency representing rheumatoid arthritis patients and doctor groups across Europe – set up a research team.

It developed guidelines to help arthritis and cancer specialists look out for joint problems caused by the new generation of cancer drugs, in the hope that patients can be treated sooner and are therefore less likely to become seriously ill.

In acute cases, treatment may need to be discontinued and replaced with something else, such as chemotherapy.

Alan Melcher, professor of translational immunology at the Institute of Cancer Research in London, says that as more people are treated with immunotherapy drugs, doctors are getting a clearer picture of the long-term side effects.

Still, it’s still worth the risk for many patients, he adds: “These are still fairly new drugs. But I have no doubt that the benefits outweigh the cons. ‘

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