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Help! I’ve developed an immunity to Botox

Leah Hardy: ‘It seems there is a small but growing number of people for whom Botox no longer works as well – or at all’ - Heathcliff O'Malley for The Telegraph
Leah Hardy: ‘It seems there is a small but growing number of people for whom Botox no longer works as well – or at all’ - Heathcliff O'Malley for The Telegraph

After months of lockdown, during which stress-induced frown lines etched themselves deeper into my skin, I was excited about the prospect of a light dusting of my favourite wrinkle-reducer, Botox.

Sarah Tonks, a highly qualified doctor who has treated me successfully in the past, popped a few injections into the ‘elevens’ between my brows and I trotted home to wait for the magic to happen.

Over the next few days, I scowled at myself furiously in the mirror, expecting that at any moment, I would find my crumpled face had become suddenly youthfully smooth.

Except it didn’t happen. After two weeks, I sent Sarah a selfie of my still ferocious frown. Baffled, she suggested I go back for a top-up. Which I did. Only for nothing to happen yet again.

Why? It seems there is a small but growing number of people for whom Botox no longer works as well – or at all. Once it was thought that if your Botox didn’t work, this was because of a ‘bad batch’, a fake product or a poor injector. But now we know that the toxin itself can trigger the production of antibodies which, in effect, may vaccinate the user against its effects.

A 2013 study found that one in 200 people developed these antibodies. And there is growing concern that as more of us fall into the ‘long time users’ camp, we are at greater risk of the treatment losing its power.

Botox – and similar wrinkle treatments – contain a highly diluted form of Botulinum toxin. Injected, it prevents chemical messages reaching muscles, weakening or inactivating them.

But the body is capable of recognising the foreign proteins in Botox and mounting an immune response against them, deactivating the toxin before it can do its work.

Dr David Jack is a plastic surgeon who specialises in aesthetics. He says: “I've seen a few patients who appear to have developed some immunity to Botox. It is estimated by Allergan, which manufactures Botox, that the incidence of this in long-term patients is around 0.3-0.6 per cent, with varying degrees of resistance.”

In 2019, experts from Merz Aesthetics which manufactures a similar botulinum toxin injectable called Xeomin, said that 13.9 per cent of patients developed antibodies against their regular botulinum toxin treatment with “ongoing treatment identified as a major risk factor.” The company also claims that 69 per cent of 2,201 users “experienced a decline in treatment effects” after at least three treatments.

If you are one of the patients for whom a wrinkle-relaxer isn’t working as well as it used to, the temptation might be to up your dose or have treatments more often. But this could just make matters worse.

Professor Nick Lowe is a consultant dermatologist at London’s Cranley Clinic. He has been at the forefront of Botox research for decades. He says resistance is more likely to occur if you have larger doses, have it too frequently or start using it too early. “The higher your cumulative dose, the greater the risk,” he says, pointing out that it is most likely to affect patients having high doses for medical reasons. But, he adds, “you’ve probably had a fair amount of it over the last 30 years.”

This is true. At 58, I’ve had a long on-off romance with Botox. Almost three decades ago I was one of the first people in the UK to be injected with the then-unknown miracle toxin.

It was for a magazine article and the photographer who came to capture the moment fainted when she saw the syringe coming towards my face.

But it worked. My nascent frown lines vanished within a week, and I looked and felt more serene. Studies have linked Botox with feeling better, possibly because it breaks a feedback look between angry or sad facial expressions and the brain. No wonder I kept coming back.

Since then, I’ve had fairly regular top-ups to nix the ‘elevens’ between my brows. Over the years doctors have injected into my forehead, around the mouth and even in my neck. Sometimes I’ve also had a bigger dose injected into the muscles of my jaw to prevent my severe tooth grinding habit.

The understanding that Botox immunity is linked to higher doses and long-term use could be bad news for the increasing number of young women seduced by claims that Botox will not only give them the glossy, glazed look of a Love Island contestant but also prevent ageing. They could spend their 20s with immobilised foreheads, only to find that when they really do ‘need’ it – their wrinkle jabs no longer work.

“I’ve seen this very early treatment called ‘prejuvenation’. But I think it is unethical,” says Lowe, who adds that treatment is better started in the 30s or later. He also says that the fad for “baby Botox” – sprinkles of low dose Botox injected over a larger area and repeated as often as every six to eight weeks – could be risky because more frequent top-ups are also linked to increased resistance. “It’s probably a better idea to have a sensible amount injected every six months,” he says.

Lowe says that previous food poisoning with Botulism may also produce antibodies that inactivate the treatment, or, more flatteringly, that I might just have a robust immune system.

So how can you prevent Botox immunity from happening to you? As well as keeping doses moderate and spacing treatments at least three to six months apart, you might consider using a different brand. Lowe says there are three versions of type A botulinum toxin wrinkle treatments licensed in the UK: Botox, Azzalure and Xeomin, also known as Bocouture.

He says that once a person develops immunity to one, they are normally resistant to them all.

However, Xeomin, which has hired Gwyneth Paltrow as its poster girl, claims that its “pure” formula is less likely to trigger resistance in the first place. Botox contains various complexing proteins, which help to keep the product stable. Xeomin still has stabilising proteins but has had the complexing proteins removed. It cites research in animals showing that complexing proteins “may have a higher potential to cause an immune response” and says that its formula produces fewer antibodies.

But Lowe is sceptical. “I don’t think there is enough evidence for this theory,” he says. “I think the toxin itself is likely to be the cause of resistance,” he says. To add to the confusion, studies have shown that some people with antibodies still respond perfectly well to Botox, and nobody knows why. And remember that total non-responders like me are still rare. Tonks says that since she moved into aesthetics in 2008, she has injected Botox literally thousands of times, but I am, to her knowledge, her first total non-responder. “You are very unlucky,” she tells me.

Tonks says I could wait it out and hope that my immunity fades over six months, although there are no guarantees. Alternatively, says Lowe, I could try a type B botulinum toxin treatment called NeuroBloc. This was developed for people who have developed immunity to type A formulations and need treatment for medical reasons. However, treatment tends to be more painful, and the effects generally last two months compared to four to six months. I’m not tempted.

After my initial shock and disappointment that my secret weapon against wrinkles no longer worked, I am counting my blessings that my Botox habit was purely for vanity rather than a medical need. And as the likes of Andie McDowell and Jodie Foster showed recently on the Cannes red carpet, lines can be beautiful and expressive. I shall continue to use good quality skincare and daily SPF and try to cultivate an inner serenity that I hope will be reflected in my now rather more mobile mid-life face.

Alternatives to Botox

If you don’t like your lines but can’t or don’t want to have Botox, what are your options?

Dr Lowe says small doses of filler in frown lines can help soften them. This needs an expert hand as wrongly injected filler close to the eyes can, in very rare cases, cause blindness. Skin-boosting treatments such as microneedling and radiofrequency may help plump up the skin, as can medical skincare such as Retin-A, combined with daily sunscreen.

Sarah Tonks suggests I might try one of the newer ‘skin boosters’ which inject tiny quantities of hyaluronic acid into the superficial layers of the skin for a dewy, plumped look or which can be placed directly into fine lines. “I like Hydrobooster which is specifically for lines and wrinkles that you’d normally treat with Botox. Short threads such as Nordyx, introduced under the skin, can encourage the skin to produce its own natural collagen. They are great for crows’ feet and are long-lasting. They also give a very natural effect and don’t affect movement.”