Brun has researched personalized treatment. Could her research be the solution for patients who don't benefit as much from medications as others?
Over 50,000 Norwegians have a chronic inflammatory disease of the joints, intestines or skin. Since modern treatment became available in the 1990s, people with chronic inflammatory diseases have had a much better life. They are free from the late effects of the diseases, such as damaged joints or leaky intestines.
Today, two out of three can be treated to feel almost completely well. Not everyone gets full help from treatment. For some, the medications stop working over time, and the disease gets worse. For those who lose the effect of the medications, everyday life can be significantly affected.
– I have conducted research to find out what really happens when treatment with such a widely used drug as infliximab no longer works, says Marthe Kirkesæther Brun.
She conducted research for her doctorate at the REMEDY research center at Diakonhjemmet Hospital.
Brun's work provides the answer to why some patients do not get sufficient effect from biological treatment with infliximab – and what can be done about it.
The results have led to new treatment guidelines in Norway.
From research to improved treatment
– These antibodies are an important reason why patients do not get a good enough effect from the treatment, explains Brun.
Research shows that the dosage of infliximab should be adjusted to the individual patient. To adjust the dosage, drug levels and antibodies in the blood are measured regularly. This is called therapeutic drug monitoring. This way of following up patients has led to more people getting better results and avoiding flare-ups of the disease.
“ Monitoring drug levels in patients to adjust dosage may therefore be useful in patients treated with infliximab. This is especially true for those who have risk factors for developing antibodies,” says Brun.
Risk factors include high disease activity, smoking, rheumatoid arthritis, and low blood levels of medications. Genetics also play a role. Brun's work documented that the tissue type antigen HLA-DQ2 increases the risk of developing antibodies.
Gold Medal for Outstanding Research Contributions
The King's Gold Medal is awarded to young researchers for scientific work that is an effective contribution to the research literature. The Rector of the University of Oslo, Svein Stølen, states:
– Congratulations to the eight very talented researchers! I am always equally proud and inspired every time the gold medals are awarded. The University of Oslo is the country's oldest and not least the best – thanks in large part to the contributions of our outstanding, younger researchers.
The award ceremony will take place during the University's annual party in the Aula on September 2nd.
From doctorate to practice
The doctoral project involved analyses of 615 patients with inflammatory bowel, joint or skin disease. The study showed that some patients develop antibodies that prevent infliximab from working.
Marthe Kirkesæther Brun's doctoral work was carried out at Diakonhjemmet Hospital and the research center REMEDY, in collaboration with Akershus University Hospital and Oslo University Hospital. She has been part of the national NOR-DRUM project, funded by Helse Sør-Øst and KLINBEFORSK.
Brun is now back specializing in rheumatology at Diakonhjemmet Hospital.
“ I want to contribute to ensuring that patients have the best possible everyday life, and I enjoy clinical practice,” she says. Clinical research and clinical practice go hand in hand at REMEDY and Diakonhjemmet Hospital, so I envision being able to continue with research as well.
Links to Brun's scientific articles:
- JAMA: Therapeutic Drug Monitoring vs Standard Therapy
- JOIM: Risk factors for anti-drug antibodies
- JOIM: HLA-DQ2 and immunogenicity
- The Lancet Rheumatology: Clinical consequences of infliximab immunogenicity
