Could long-term injections replace daily pills that treat chronic illnesses?

A new medication, given twice a year, could reduce the number of patients taking daily tablets

Zilebesiran only has to be administered once every six months as an injection, in contrast to most blood pressure medications, which should be taken every day as tablets. Getty Images

For all the money and effort that goes into developing drugs, they can be rendered ineffective if they are not taken properly.

Rates of non-adherence, which may involve skipping doses or taking them at the wrong time, can be around 50 per cent among patients prescribed medication for chronic illnesses.

It is a key reason why drugs underperform in the real world compared to when they are tested in carefully controlled trials, where adherence tends to be higher.

Aside from the wasted spending on medication, the effects of non-adherence are significant. A study published in May in Nature Reviews Drug Discovery reported that it results in the deaths of about 125,000 patients in the US alone each year.

“Poor adherence is also estimated to cause 10 per cent of all hospitalisations and underlies $100–300 billion of avoidable healthcare costs annually,” the study said.

This is why recent trial results indicating that a drug called Zilebesiran, effective at treating blood pressure, have sparked interest.

Zilebesiran only has to be administered once every six months as an injection, in contrast to most blood pressure medications, which should be taken daily as tablets.

“There’s a lot of evidence that if we have a drug-delivery regime which works and is given once and lasts for three months, six months or whatever, it’s much, much better because, one, there’s regularity in that dose and two, the dose is maintained at the correct level,” said Dr Bharat Pankhania, a senior clinical lecturer at the University of Exeter Medical School in the UK.

“So long-term medications are a great advance in the scientific technology whereby it’s a case of take and forget.”

Drug holidays

Failing to take tablets properly can be a particular problem for conditions, such as high blood pressure, where patients typically do not have symptoms.

“If you are a chronic patient, the tendency is as you become asymptomatic if the treatment works, you think, ‘I’m feeling well, why should I take the drug?’ This is a very known effect with, for example, hypertension,” said Professor Oscar Della Pasqua, professor of clinical pharmacology and therapeutics at University College London.

“Hypertensive patients don’t have symptoms and you think ‘I will stop taking the drug,’ or you stop taking the drug as you should, or you have dose gaps – you don’t have your new prescription, you don’t go to the pharmacy – we call drug holidays.

“Altogether, this variable adherence pattern can lead to potential complications, recurrence of a condition and so on.”

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“With hypertension, the complications can include an increased risk of stroke, a potentially disastrous outcome for the patient and something that results in increased costs for the healthcare provider,” Prof Della Pasqua said.

Patients stop taking medicine

There are varied reasons why patients do not take their drugs as they are meant to.

A 2011 review paper in Mayo Clinic Proceedings noted that some causes relate to the patient, such as a lack of understanding about the medication or a lack of involvement in decision-making about treatment.

Unpleasant side effects may also cause patients to stop taking their medication.

Other reasons are linked to doctors, who may prescribe a complex treatment regimen or not explain adverse effects properly. Dealing with multiple doctors may also lower adherence.

“Believing that medication non-adherence is the 'fault' of the patient is an uninformed and destructive model that is best abandoned,” the study authors wrote.

Dr Bharat Pankhania, a senior consultant on communicable disease control in the UK. Courtesy: Dr Pankhania

Certain patients have conditions that may make them less likely to take their medication. Among those likely to not follow a course are those with Alzheimer’s disease, where rates of non-compliance have been estimated to be between 17 per cent and 100 per cent. Those with psychosis are also less likely to follow a course of medication.

“A lot of people with psychosis have erratic lifestyles or erratic behaviours. It’s not that they’re bad people, it’s the way their illness is,” Dr Pankhania said.

Longer-lasting

The answer, in some cases, is a medication given as a depot injection, which involves administering a liquid that releases the drug slowly. With antipsychotic medications, the patient may receive an injection once every several weeks or even less often.

Depot injections may be given for a wide variety of other purposes, such as birth control, in which case they may last around three months, and to combat prostate cancer, which lasts as long as six months.

As well as improving adherence, drugs administered less often by injection or IV infusion offer an opportunity for a healthcare professional to see the patient.

“That’s where you combine intervention with a follow-up of the patient’s condition,” Prof Della Pasqua said.

“That aligns the visit with the GP or the nurse, so you have a very regular interaction with your healthcare professional.”

Just as providing longer-lasting medication reduces the number of times people have to take a drug, combining vaccines can also cut the number of injections required.

This is often done with vaccines for children, such as the measles, mumps and rubella vaccine. In some instances, a single injection may offer protection against as many as six diseases.

However, there may be downsides associated with medications that are given less frequently.

If an injection lasts for months, it becomes harder to adjust the dosage. With a hypertension drug, there could be the risk that patients experience episodes of low blood pressure.

Better adherence is often seen as a benefit of medications that need to be taken only infrequently, but Dr Andrew Freedman, a reader in infectious diseases at Cardiff University in the UK, highlighted a pitfall.

“If someone is not very good at taking their drugs if you miss a once-every-six-month dose, you are not getting it at all,” Dr Freedman said.

“If you miss the odd daily dose of a blood pressure medication, it’s going to be less problematic.”