The doctoral thesis shows a connection between the patient's immune response and the effect of treatment in inflammatory diseases of the joints and intestines. The research has contributed to a greater understanding of how the immune system affects the effect of biological medicines and COVID-19 vaccines in people with such diseases.
The new doctor with supervisors, assessment committee and dissertation chair, from left Gert-Jan Wolbink, Espen A. Haavardsholm, Ingrid Jyssum, Guro L. Goll, Silje W. Syversen, Nils Bolstad, Inger Gjertsson and Elisabeth Gulowsen Celius. Anne Spurkland was not present when the picture was taken. Photo: Diakonhjemmet Hospital, Kathrine Daniloff
In their thesis "Immunogenicity of therapeutics in inflammatory joint- and bowel diseases", Ingrid Jyssum and colleagues reveal findings of great importance for patients with chronic inflammatory diseases of the joints and intestines. Most people with this type of disease require long-term treatment with immunosuppressive drugs. The immune system of these patients strongly influences how both vaccines and drugs work.
The research led to specific vaccine recommendations
Jyssum has revealed that they need multiple doses of the COVID-19 vaccine to achieve the same protection as healthy people. These research results were important information for public vaccine recommendations during the corona pandemic.
– Thanks to a large patient material, we were able to investigate the effects of different, specific biological medicines. Some biological medicines caused patients to have a poor vaccine response, even with repeated vaccination. These findings helped health authorities to make good vaccine recommendations for patients who used immunosuppressive medicines during the COVID-19 pandemic, explains Jyssum.
Data material comes from patients at Diakonhjemmet Hospital with inflammatory joint diseases, as well as patients from Ahus with inflammatory bowel diseases. 2300 patients have participated.
Antibodies prevent medicine from working
Jyssum and colleagues have also conducted studies of adalimumab, the most widely used biological drug in the world for inflammatory joint diseases. Today, it is dosed the same for everyone, regardless of factors such as weight. A significant proportion of patients develop antibodies to adalimumab, which reduces the drug's effectiveness.
– We found that 10 percent of the patients had developed antibodies to the drug, already after 3 months. This gave them a poorer effect of the treatment. We also found that the measurable level of adalimumab in the blood was relevant to the treatment effect. This indicates a need for more customized dosing, based on individual response patterns, emphasizes Jyssum.
She explains that these research results can provide a basis for personalizing treatment with biological drugs to the individual even more than today, in order to achieve good treatment results.
Activation of the immune system
Immunogenicity is the ability of a foreign substance to activate the immune system. Depending on the active substance in question, immunogenicity can be a desired or an undesired effect. Vaccines are designed to elicit a desired immune response, while an immune response directed at biological drugs can destroy the treatment effect we are looking for.
–Since biological drugs are very important in the treatment of many inflammatory diseases, it is important to gain knowledge about how immunogenicity prevents these drugs from working well, explains Jyssum.
Clinical research
Jyssum started working as a physician at the Clinic for Rheumatology at Diakonhjemmet Hospital in 2019. From January 2021 to December 2023, she has had a 100 percent position as a research fellow, with financial support from South-Eastern Health.
Jyssum's work is an important step towards better and more personalized treatment strategies for patients with serious inflammatory diseases.
“Our research highlights the need to monitor and possibly adjust how biologic drugs are administered to maximize their efficacy and improve outcomes for patients,” says Jyssum.
The way forward
Jyssum is now back in the clinic, but divides her working time equally between clinic and research. As a 50% postdoctoral fellow in the EU project SQUEEZE, she will be the national coordinating investigator in the RA-DRUM study, a multinational study, which is coordinated from the REMEDY center at the hospital. She is also involved in further collaboration between REMEDY and the Norwegian Institute of Public Health to study how vaccines should be given to people using immunosuppressive medications.
Trial lecture title
"Targeting immunological memory in autoimmune disease: Novel opportunities for immunotherapy"
Supervisors, assessment committee and dissertation supervisor
Her main supervisor has been Guro Løvik Goll, and co-supervisors have been Silje Watterdal Syversen, Nils Bolstad and Espen A. Haavardsholm. The assessment committee consisted of Gert-Jan Wolbink (Amsterdam University Medical Centre, Free University Amsterdam, Netherlands), Inger Gjertsson (Gothenburg University, Sweden) and Anne Spurkland (UiO), with Elisabeth Gulowsen Celius as the defence chair.
The articles from the doctoral project
https://doi.org/10.1016/S2665-9913(21)00394-5
