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Measuring biological drugs and anti-drug antibodies in patients



With new technology, researchers will make it possible for doctors to prescribe medicine containing biologicals based on an assessment of the levels in the individual patient. This kind of pharmaceutical is often characterised by being expensive, and the effort will therefore benefit both individual patients and hospital finances.

In recent years, biological drugs for diseases such as arthritis and cancer have become popular in the health sector due to positive results in patient treatment. This type of medicine is based on particular proteins known as therapeutic antibodies, and these are extremely difficult and expensive to manufacture.

Sales of therapeutic antibodies are increasing rapidly and figures this year have reached more than DKK 370 billion globally. There is much to indicate that this trend will continue as researchers from all over the world get better at designing more antibodies with specific properties.

“Research in biological medicine is in full swing at a global level. We’ve only seen the beginning when it comes to using therapeutic antibodies in the health sector, and we’re facing a future in which we’ll see the introduction of many more,” says Associate Professor Peter Kristensen, who has years of experience in developing new antibodies.

When is enough enough?
For example, a one-year treatment of a patient’s rheumatoid arthritis symptoms can cost as much as DKK 200,000, which means there is very good reason to see whether doctors can become better at prescribing the right dose, according to Associate Professor Kristensen.

“It’s very difficult today to find out whether the treatment with therapeutic antibodies will have any effect at all on the individual patient, or how much medicine the patient regularly needs to achieve the optimal effect. If there is just ten per cent too much on average, this could provide an interesting overall financial savings potential for the hospitals, which can benefit other patients,” he says.

The researchers at Aarhus University have entered into a collaboration with the Danish Rheumatology Biobank (Dansk Reuma Biobank) and, in the coming years, they will develop new methods for dosing therapeutic antibodies more accurately on the basis of a simple blood test. The idea is to measure the amount of medicine remaining in the bloodstream before giving the next injection.

This might sound straightforward, but it is actually far from it.

“If you want to give the right dose, you have to take into account how much medicine is still in the body. This is complicated by the fact that therapeutic antibodies are designed to resemble the body’s own antibodies,” says Associate Professor Kristensen.

He will initially develop a method for measuring the therapeutic antibodies used to treat symptoms of rheumatoid arthritis. The method can easily be adapted to other types of biological medicine.

One antibody out of billions
For this purpose, the researchers will use a library of billions of recombinant produced antibodies, and the researchers have developed technologies that make it possible to identify one single antibody from among the multitude, and subsequently optimise it in the laboratory.

They have previously used the technology for research into conditions such as cancer and ageing, and they will now use it to find exactly the recombinant antibody required to bind to rheumatoid arthritis medicine and not to the body’s own antibodies.

“We know we can find recombinant antibodies in our library with such specific properties that they can bind to different types of biological medicine without also binding to the naturally occurring antibodies in the body. One of the possible points of attack is the sugars that attach themselves to the antibodies in the blood. They’re so small that we can’t characterise them, but we know that the specific action mechanisms of the antibodies are affected,” says Associate Professor Kristensen.

Once the researchers have selected the relevant recombinant antibodies, there is still quite a bit of engineering work required to integrate them in a measuring instrument that is both inexpensive and precise. This could be a test similar to the one used to measure blood sugar levels. Here the patient pricks a small hole in the skin and applies a drop of blood to a strip.

By carrying out cheap and frequent measurements, the patient will know with a great degree of accuracy when it is time for the next injection with the expensive biological medicine.

Cheap tests can reduce overdoses
The measuring method will also assist doctors in their assessment of the effect of the medical treatment. This is because therapeutic antibodies do not work on all patients and the effect may decrease with time.

This happens when the body begins to recognise the medicine as a foreign substance. In this process, new antibodies are developed against the biological medicine which therefore stops working.
“If we can measure when the new antibodies start to fight the biological medicine, we’ll have a better chance of giving medicine that works for individual patients. This way, we’ll be able to provide more reliable treatment, and we can cut down on the consumption of very expensive medicine in cases where it has no effect anyway,” says Associate Professor Kristensen.

PHOTO TOP: Using new technology, researchers will make it possible to measure when it is time for the patient’s next injection with expensive biological medicine. They hope to be able to provide better individual treatment and cut down medical expenses. The photo shows Associate Professor Peter Kristensen who is developing a new method for dosing therapeutic antibodies in treatment of patients with rheumatoid arthritis. (Photo: Anders Trærup)