The doctoral work shows a connection between the patient's immune response and treatment effect in inflammatory diseases of the joints and intestines. The research has contributed to 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 supervisor, 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 photo was taken. Photo: Diakonhjemmet hospital, Kathrine Daniloff
In her thesis "Immunogenicity of therapeutics in inflammatory joint- and bowel diseases", Ingrid Jyssum and colleagues uncover findings of great importance for patients with chronic inflammatory diseases of the joints and bowel. Most people with this type of disease need long-term treatment with immunosuppressive drugs. The immune system in these patients has a strong influence on how both vaccines and drugs work.
The research led to concrete vaccine recommendations
Jyssum has discovered that they need several doses of the COVID-19 vaccine to achieve the same protection as healthy people. These research results were important information for the public vaccine recommendations during the corona pandemic.
- Thanks to a large patient material, we were able to examine the effect of various, specific biological medicines. Some biological medicines caused patients to have a poor vaccine response, even with repeated vaccinations. These findings helped the health authorities to make good vaccine recommendations for patients who used immunosuppressive drugs during the COVID-19 pandemic, explains Jyssum.
Data material comes from patients at Diakonhjemmet hospital with inflammatory diseases of the joints, as well as patients from Ahus with inflammatory diseases of the intestine. 2,300 patients have participated.
Antibodies prevent medicine from working
Jyssum and colleagues have also carried out studies of adalimumab, the most widely used biological drug in the world against inflammatory diseases of the joints. Today, it is dosed the same for everyone, regardless of factors such as e.g. weight. A significant proportion of patients develop antibodies against adalimumab, which reduces the drug's effectiveness.
- We found that 10 per cent of the patients had developed anti-substances (antibodies) against the medicine, already after 3 months. It gave them a worse 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 the 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 against biological drugs can destroy the treatment effect we are looking for.
- Since biological medicines are very important in the treatment of many inflammatory diseases, it is important to gain knowledge about how immunogenicity prevents these medicines from working well, explains Jyssum.
Clinical research
Jyssum started working as a doctor at the Rheumatology Clinic 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 Helse Sør-East.
Jyssum's work is an important step towards better and more personalized treatment strategies for patients with serious inflammatory diseases.
- Our research emphasizes the need to monitor and possibly adjust how biological medicines are administered, in order to maximize their effect and improve outcomes for patients, says Jyssum.
The way forward
Jyssum is now back in the clinic, but divides his working time equally between the clinic and research. As a 50% postdoctoral fellow in the EU project SQUEEZE, she will be the national coordinating examiner 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 FHI to study how vaccines should be given to people who use immunosuppressive drugs.
The title of the trial lecture
"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 assistant 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, The Netherlands), Inger Gjertsson (Gothenburg University, Sweden) and Anne Spurkland (UiO), with Elisabeth Gulowsen Celius as dissertation supervisor.
The articles from the doctoral project
https://doi.org/10.1016/S2665-9913(21)00394-5
