Cand. Med. Ingrid Egeland Christensen has recently completed her doctorate at the Diakonhjemmet Hospital and the research center REMEDY. The dissertation, Serious infections in patients with inflammatory joint diseases, sheds light on the increased risk of serious infections in patients treated with biological drugs.
In the picture you see, from left, Tore Kvien, Siri Lillegraven, Ingrid Egeland Christensen, head supervisor Sella Arrestad Provan and Till Uhlig.
Christensen's research shows that patients with inflammatory joint diseases, who are treated with biological drugs, have a significantly higher risk of serious infections.
Biological drugs are central to the treatment of inflammatory diseases of the joints and intestines. At the same time, the drugs dampen the immune system and increase the risk of a common infection becoming serious.
- These patients receive clear information that they must take a break from the medication if they get an infection, says Christensen.
Higher risk than the general population
The research shows that the risk of serious infections is twice as high as in the general population. It also seems that the risk remains high while one is undergoing treatment. Patients with rheumatoid arthritis are also at greater risk of infections compared to those with psoriatic arthritis or spondyloarthritis.
Research influences clinical practice
Christensen's research has already influenced the treatment of patients with inflammatory joint diseases at Diakonhjemmet Hospital. Increased awareness of the risk of infection has strengthened the awareness of vaccinating patients receiving biological treatment to prevent an infection from becoming serious.
COVID-19 and vaccination response
During the COVID-19 pandemic, Christensen participated in a study that investigated how patients with inflammatory diseases responded to corona vaccination. The study showed that these patients had a weaker antibody response and lost the antibodies faster than healthy people. The findings have contributed to recommendations for more frequent vaccination doses for this patient group.
Although Christensen is now looking forward to working in the clinic full-time, she has a strong desire to continue with clinical research in the future.
- REMEDY is an internationally recognized research centre, and it is certainly something I would like to be a part of again, in the long term, she says.
More about the doctorate
Cand. Med, Ingrid Egeland Christensen (PhD) defended her dissertation on 25 September 2024. Before she defended her doctoral thesis, she gave her trial lecture, with the stated topic: "Risks of malignancy due to rheumatoid arthritis and the modification of risk associated with disease‐modifying antirheumatic drug therapy”. The doctorate is affiliated with the University of Oslo, Department of Clinical Medicine.
Supervisors and dissertation
Christensen's doctoral work was supervised by Sella Aarrestad Provan, Till Uhlig, Tore Kvien and Siri Lillegraven. The assessment committee consisted of Kevin Winthrop, Mari Hoff and Berit Flatø, while the defense supervisor was Erik Øie.
Berit Flatø, Kevin Winthrop, Ingrid Egeland Christensen, Mari Hoff and Erik Øie
A doctorate from Diakonhjemmet hospital and the REMEDY centre
The doctoral work is based on the Diakonhjemmet hospital and the REMEDY centre. In addition, there has been close collaboration with the department of gastroenterology at Akershus University Hospital in connection with the planning and implementation of the Nor-vaC study. It is also important to highlight all departments that have been and are involved in the NOR-DMARD study.
The purpose of this doctoral project has been to map the incidence and to investigate the risk of serious disease in patients with inflammatory arthritis disease.
- As the treatment of arthritis has developed significantly over the past 25 years, we wanted to investigate whether this has had an impact on the risk of serious infections - and whether this has changed over time, says Christensen.
She explains that they also wanted to investigate when there is the greatest risk of serious infections after the patient has started treatment with a biological medicine.
- We have therefore compared the incidence and risk between patients with arthritis and the control population and compared the risk between different types of inflammatory joint disease during treatment with biological drugs, she explains.
This doctoral project analyzes data from the longitudinal observational study NOR-DMARD.
The NOR-DMARD register
The doctoral work related to infection risk is based on data from the NORwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) study, a registry with more than 10,000 patients with inflammatory arthritis disease.
NOR-DMARD was established in 2000 at Diakonhjemmet Hospital, and today four hospitals participate. Since its establishment, over 18,000 individual treatment courses have been registered in around 11,000 patients with inflammatory arthritis disease. In 2017, REK gave permission to link patients in the NOR-DMARD register to the Causes of Death Register and the Norwegian Patient Register, and in 2019 each patient in the NOR-DMARD was linked to 10 randomly selected controls who were matched for age, gender and place of residence. Until this work, all research into serious infections and biological treatment has come from data on populations outside Norway, which are not necessarily completely comparable.
Greater risk of infections in rheumatoid arthritis
The first article in this PhD project was published in 2021 in the Annals of Rheumatic Diseases. Here, the incidence of serious infections is compared between patients with rheumatoid arthritis and psoriatic arthritis who receive treatment with biological drugs within the tumor necrosis factor inhibitor (TNFi) group.
- We found that patients with psoriatic arthritis had a clearly lower risk of serious infections compared to patients with rheumatoid arthritis. We believe this finding is of clinical importance, she emphasizes.
Equally great risk of serious infection over time
NOR-DMARD has included patients for around 24 years, and in the second article we found that the risk of serious infection in patients with arthritis who receive biological treatment has remained unchanged since 2009.
The researchers also investigated whether the risk of serious infections in patients with arthritis has changed over time compared to the general population.
- We found that patients with arthritis who are treated with biological drugs have approximately twice the risk of serious infections than the general population, she says.
They found that the risk of serious infection has not changed over time, either within each patient population or compared to the general population. They also found no evidence that the risk changes over time during a course of treatment.
Poorer antibody response to vaccination
As part of his doctoral work during the Covid-19 pandemic, Christensen has participated in the Nor-vaC study. This longitudinal observational study is based on Diakonhjemmet hospital and Akershus University Hospital. It was established to map the response to Covid-19 vaccination in patients with inflammatory rheumatic joint disease and inflammatory bowel disease, who are treated with immunosuppressive drugs.
Data from the Nor-vaC study was used to investigate the duration of the antibodies formed after two doses of corona vaccine, and compared the duration of the antibody response in patients against healthy controls. The work has shown that patients with inflammatory disease in the joints or intestines had a poorer antibody response to vaccination, and that the patients lose their antibodies faster than healthy controls. The findings were important information in the discussion about vaccination strategy and booster doses, and supported the need for repeated vaccination of this patient group.
Improved patient care
Christensen's research has led to improved treatment and follow-up of patients with inflammatory diseases who are treated with biological drugs.
