New drug therapy that could beat the misery of hay fever forever
New drug therapy that could beat the misery of hay fever forever: A combination of two immunotherapy drugs are being trialled as a long-term solution for the condition
As a keen gardener, Steve Moore would have liked to spend his Sunday afternoons mowing the lawn.
But this task has to be done by his wife Abi, 45, a commercial director, because his hay fever is so severe he can’t even go outside when his neighbours are cutting the grass, let alone do the job himself.
‘Within minutes my eyes are red and streaming,’ says Steve, 47, an operations director from Epsom in Surrey.
‘I’ve had bad hay fever since I was at primary school and remember being collected before the end of lessons by my mum because my eyes were streaming so much I couldn’t see.
The trial was launched last year and it is hoped that the treatment — daily tablets and having an injection every two weeks for two years — will take effect within four months
‘It has stayed with me ever since and limits what I can do. I’ve had to face a job interview panel with puffy eyes and a runny nose and I can’t do any contact sport in the summer because I can’t wear my contact lenses as my eyes are so sore.’
Sometimes, his symptoms are so bad he has to drive his car to work rather than use his electric motorcycle as usual ‘so that I can cocoon myself from the pollen and take advantage of the air-conditioning’.
But Steve — father of Jessica, 17, and Austin, eight — is hopeful that this year will be different.
He is one of more than 100 people taking part in a new trial at the Royal Brompton Hospital in London that is testing a combination of two immunotherapy drugs — Grazax (generic name lyophilisate) and Dupixent (dupilumab) — as a long-term solution for the 13 million people in the UK blighted by hay fever.
The trial was launched last year and it is hoped that the treatment — daily tablets and having an injection every two weeks for two years — will take effect within four months.
Steve, who started the treatment in November, does not have long to wait to see if the new therapy has worked because the hay fever season has already begun thanks to the unseasonably warm weather.
I had it so severely my nose collapsed
Julie McBride, 47, from Northampton, works in pastoral support at Northampton University.
There was a point in my life when I hated the spring and summer because it meant one thing: hay fever.
Some of my earliest memories, from when I was about ten years old, are of coming home from school and getting straight in the shower to wash off the pollen. Then I would lie on my bed with a wet towel over my head to relieve my streaming eyes and soothe my swollen nose.
Julie McBride, 47, from Northampton, works in pastoral support at Northampton University. She says: ‘There was a point in my life when I hated the spring and summer because it meant one thing: hay fever’
As I got older, I tried everything to help, even acupuncture, but nothing ever touched my hay fever. At times it felt as if it was controlling my life.
I’d wake in the night with a runny nose, unable to breathe. I’d have to strip my bedding and wash several times to get rid of the pollen. But even that only helped for a few hours.
I’d keep my car windows up even on sweltering days, and couldn’t attend summer events without planning in advance how I would wipe my eyes and streaming nose.
In 2016, after repeated visits to my GP, they referred me to an allergy specialist. He ran pinprick tests that confirmed I was allergic to tree pollen and would get hay fever from March to September.
Antihistamine medication did nothing. I went back to my allergy specialist that year as my symptoms worsened.
My nose felt almost permanently blocked and a scan showed that my septum (the ridge of cartilage that separates the nostrils) had collapsed under the pressure on my sinuses, caused by hay fever. I had to have surgery to rebuild it.
In 2019, my allergy doctor sent me a letter about a trial of an immunotherapy tablet which might desensitise me to pollen, and asked if I wanted to take part. I jumped at the chance.
I had to put a medicine that contained pollen, a pill called Grazax, under my tongue every day for three years.
I started taking it at the end of summer, so didn’t feel much of a benefit. But the following March I didn’t have any hay fever symptoms. No itchy nose, no streaming eyes — nothing. It had worked.
That summer was amazing. It was the first time I could go outdoors without psyching myself up.
I finished taking the medication last year because the trial ended. I wish I could have stayed on it for ever.
When I stopped taking the pills, I had some itchiness and streaming eyes, but nowhere near as bad as it was before.
I am hoping this year won’t be as bad either. If my hay fever does return, I’ll be begging to go back on the medication.
After 40 years of suffering, it was the only thing that took away my hay fever misery.
Interview: JULIE COOK
‘A warm February — as we’ve had — tends to lead to an earlier onset of the birch pollen season,’ says Dr Beverley Adams-Groom, a pollen forecaster at Worcester University.
But that doesn’t mean the season will be worse. We tend to have ‘bad’ tree pollen years — where more high pollen days trigger worse symptoms in more people — every other year as pollen develops in two-yearly cycles.
Forecasters predict that the hay fever season will be milder this year compared with 2021. But even if the predictions are correct, millions will still be affected by debilitating hay fever symptoms — sneezing, running nose and itchy eyes, as well as fatigue.
However, hay fever is often not taken seriously, says Stephen Durham, a professor of allergy and respiratory medicine at Royal Brompton and Harefield Hospitals and Imperial College London.
‘It is often trivialised by doctors and family members who don’t have it, but it really can have a major impact on people’s quality of life and performance at school or in the workplace,’ he says.
‘Hay fever often interferes with sleep quality and prevents outdoor activities during what, for most of us, is the best time of the year. It may also be associated with asthma with more serious and occasionally life-threatening consequences.’
Research published in the Journal of Allergy and Clinical Immunology in 2007 showed that teenagers who had hay fever symptoms on the day they were sitting an exam were 40 per cent more likely to drop a grade from their predicted exam results.
Hay fever occurs when an allergen — commonly grass or tree pollen — sends the body’s immune system into overdrive. Sufferers have high levels of a particular antibody called immunoglobulin E (IgE) that binds to ‘mast’ cells in the lining of the nose.
When pollen comes into contact with these mast or signalling cells, this alerts the IgE antibodies and, in turn, triggers the explosive release of chemicals such as histamine from the mast cells to attack or get rid of the allergen — in the process causing the telltale symptoms of sneezing, runny nose and sore and streaming eyes.
Earlier season, but could this year be milder?
Scientists are able to predict months in advance how severe the hay fever season is likely to be, as well as when it will start.
Its severity is based on a number of factors, including the pre-season growing temperatures for plants that trigger hay fever, as this determines how much pollen they will produce, says Dr Beverley Adams-Groom, a pollen forecaster at the University of Worcester.
‘Birch tree pollen is produced in the previous June or July, when a spell of good weather can increase pollen production,’ she says. ‘Grass pollen production is higher when April and May are warm and wet.’
So, based on last year’s temperatures, it looks as if we’re due a milder hay fever season.
A warm February normally means an earlier birch pollen season, as we are already experiencing this year. But that doesn’t necessarily make the season end sooner. What matters for the longevity of the season is how warm it is from now.
‘If the weather for a particular plant is warm and sunny, allowing plenty of pollen dispersal, then the season is more likely to be shorter as the flowers become exhausted more quickly,’ says Dr Adams-Groom.
The grass pollen season is usually shorter when the weather is good during June and early July, she adds. ‘During cool or wet weather, the grasses close their flowers and sit tight until better weather returns.’
It has previously been suggested that these symptoms can be confused with Covid, but they are quite different, says Professor Durham. ‘With Covid, the main symptoms are cough, fever and loss of smell — although both may be associated with general symptoms of fatigue and malaise.’
In fact, hay fever sufferers may actually be protected against Covid. They have been shown to have fewer of the receptors in the lining of their noses and bronchial tubes on to which the spike protein of the Covid virus can latch.
Hay fever affects one in four Britons, although the number is rising, partly as a result of rising temperatures which boosts pollen levels. While most people get it in the spring and summer, some people are affected all year round.
‘Grass pollen is the most common trigger but tree pollen is becoming an increasing problem, owing to climate changes and the increased popularity of birch trees in urban areas,’ says Professor Durham.
For the all-year-round sufferers, the problem is hazel and alder tree pollen in late winter. Between 40 to 60 per cent of hay fever sufferers find symptoms ease with over-the-counter medicines.
Antihistamine tablets (such as cetirizine, brand name Zirtek, and loratadine, brand name Clarityn) block the effects of histamine by locking on to histamine receptors in the nose and throat.
Corticosteroid nasal sprays such as beclomethasone (brand name Beconase) and fluticasone (Flixonase) work by suppressing the immune response to grass pollen in the nose.
For severe eye symptoms, eye drops containing sodium cromoglicate (brand name Opticrom) block the release of histamine from mast cells in the eye, although these have to be repeated several times daily; olopatidine (Opatanol) eye drops only need to be given twice daily. Many people don’t realise they need a combination of treatments to keep symptoms at bay.
The majority with moderate hay fever need a regular daily antihistamine as a preventative treatment plus a steroid-based nasal spray and eye drops, says Dr Timothy Watts, a consultant adult allergy specialist at The London Clinic and the Homerton Healthcare NHS Foundation Trust.
When it comes to choosing an antihistamine, Professor Durham recommends using the more modern non-drowsy versions such as cetirizine and loratadine: ‘This is what I take for my hay fever’, he says, adding: ‘The generic versions of cetirizine and loratadine on the bottom shelf of the chemist are just as good and less expensive.’
Steroid nasal sprays should be taken ‘in the early morning and possibly evening as well, depending on the type of spray or prescription’, says Dr Watts.
‘It is very important that patients take this treatment every day, throughout the whole hay fever season, and where possible start two to three weeks before the season kicks off or before you have any symptoms, to prevent an initial attack happening.’
If over-the-counter medications don’t help, a GP can prescribe stronger versions, while a specialist can prescribe immunotherapy injections and pills, which are aimed at effectively ‘retraining’ the immune system. The jabs introduce minute but increasing doses of grass pollen extract via weekly then monthly injections for several years to build up the body’s tolerance to grass or tree pollen.
The idea is that this desensitises the immune system’s response to the allergen, blocking the action of mast cells so that the body no longer reacts, or has a reduced reaction, in some cases making symptoms disappear. While these injections are effective, they may cause an allergic reaction so have to be given in specialist clinics.
Recently, another form of immunotherapy — grass pollen tablets which can be taken at home — have been shown to be a safer alternative. Such treatments are effective for people with severe hay fever and the beneficial effects last at least two years after stopping the treatment.
The pollen behind your symptoms
January to April: Hazel and alder tree pollen (a small proportion of hay fever sufferers affected).
Late March to late May: Birch pollen (25 per cent affected).
April to June: Oak pollen (20 per cent affected).
May to Au gust: Grass pollen (95 per cent affected).
End of June to September: Weed pollen (20 per cent affected).
A 2007 Cochrane review of 51 studies involving 2,871 patients with hay fever who underwent desensitisation treatment found it resulted in ‘significant reductions in symptom scores and medication use’.
‘Exposing people to grass pollen in this way is a very effective treatment for the 10 per cent of people who really have debilitating hay fever,’ says Professor Durham. ‘The treatment works within two to four months. However, you need to treat patients for three years in order to get a big improvement in their hay fever for several years afterwards.’
Accessing these treatments — widely used in Europe and the U.S. — can be difficult in the UK because they need to be administered or prescribed by an allergy specialist, and they are in short supply.
A House of Lords report in 2007 recommended that every region should have a specialist NHS allergy centre led by at least two adult and two paediatric allergy consultants.
Yet still there are only eight NHS centres led by a full-time allergy specialist across the country.
Perhaps not surprisingly, patients with hay fever in Europe and the U.S. are 200 times more likely to receive immunotherapy than UK patients. In Germany, 7 per cent of adults with hay fever are treated with immunotherapy, compared with 0.03 per cent in the UK.
The new research by Professor Durham is investigating whether adding dupilumab injections, given fortnightly, to the existing immunotherapy pill Grazax for grass pollen allergies will make the treatment more effective, longer-lasting and shorten the desensitisation treatment course to two years.
Dupilumab is a monoclonal antibody — a laboratory-produced molecule engineered to target parts of the immune system that have gone into overdrive.
‘Specifically, it targets two chemicals called cytokines — interleukin 4 and 13 — by blocking their common receptor. These cytokines are produced by cells that drive the allergic response,’ says Professor Durham.
Researchers hope that adding the two treatments, that act in different ways, together will make the treatment more effective and longer-lasting. ‘This could mean patients are able to take the drugs for a shorter period of time but with longer-lasting benefits,’ says Professor Durham.
Steve joined the trial — the GRADUATE study, funded by the Immune Tolerance Network of the National Institutes of Health in the U.S. — last year after hearing about it on the radio.
Although he had tried different over-the-counter and prescription treatments over the years, none really worked. ‘My GP didn’t see it as a credible condition as the symptoms were seasonal, even though they were having a significant impact on my life,’ he says.
At the height of the season, he is so badly affected that his social life virtually grinds to a halt as he shelters inside. ‘So when I heard the advert on the radio for the trial, I thought I’d give it a go.’
The 108 participants on the study will be split into three treatment groups; Grazax and dupilumab, Grazax and a placebo injection, and two placebo treatments.
Neither the patients nor the researchers know what treatment the patient is getting.
The participants will record their symptoms via an app once the hay fever season starts.
During the two years on treatment, and one year after, they will also undergo blood tests every three months and a nasal allergen challenge (where a dose of grass pollen is blown up each nostril to see how the patient responds).
Results are expected in 2025.
Another new treatment being investigated for grass pollen hay fever is a drug known as IRL201104, which resets the immune system.
Participants on the ARIAS trial, being carried out at Guy’s and St Thomas’ Hospital in London, will receive six doses of either this experimental drug or a placebo over three months.
It is hoped that the study will provide evidence about how the new treatment works, the optimal dose and how long the treatment needs to be given.
With the hay fever season upon us, Dr Adams-Groom says anyone who is affected should start their treatment now.
‘This will prevent you getting the first really bad attack of hay fever that would then make you more sensitive,’ she says.
And if you don’t want to take a pill, she suggests trying barrier creams and gels that you rub around the nostrils to catch pollen before it can enter the nose — and wearing a face mask that covers the mouth and nose during the summer months because it’s ‘the pollen getting up the nose and triggering a histamine reaction that causes all the symptoms’.
‘Also, try to avoid bringing pollen into the home on clothing, washing and pets. Change clothing when coming in from outside, dry clothes indoors and wipe pets down with a damp cloth after being outside.’
Meanwhile, Steve thinks it is likely that he is on the active drug arm of the trial, rather than the dummy treatments, because so far he hasn’t had even a twitch of a sneeze, even though the season has started.
He hopes this will finally be the end of more than 40 years of hay fever misery.
‘To have a dramatic improvement in hay fever symptoms after all this time would be quite something,’ he says with some understatement.
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