Cand. Med. Ingrid Egeland Christensen has recently completed her doctorate at Diakonhjemmet Hospital and the research center REMEDY. Her thesis, Serious infections in patients with inflammatory joint diseases, highlights 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, main 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.
Biologic drugs are central to the treatment of inflammatory diseases of the joints and intestines. At the same time, the drugs suppress 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 their medications if they get an infection, says Christensen.
Higher risk than the general population
Research shows that the risk of serious infections is twice as high as in the general population. It also appears that the risk remains high while on treatment. Patients with rheumatoid arthritis are also at higher 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 infection risk has strengthened awareness of vaccination in 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 examined how patients with inflammatory diseases responded to the coronavirus vaccination. The study showed that these patients had a weaker antibody response and lost their antibodies more quickly than healthy individuals. The findings have contributed to recommendations for more frequent vaccination doses for this patient group.
Although Christensen now looks 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 center, and it is definitely 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 doctoral thesis on 25 September 2024. Before defending 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 doctoral degree is affiliated with the University of Oslo, Department of Clinical Medicine.
Supervisors and public defense
Christensen's doctoral thesis 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 chair was Erik Øie.
Berit Flatø, Kevin Winthrop, Ingrid Egeland Christensen, Mari Hoff and Erik Øie
A doctorate from Diakonhjemmet Hospital and the REMEDY Center
The doctoral work is based at Diakonhjemmet Hospital and the REMEDY Center. 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 illness in patients with inflammatory arthritis.
“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 the risk of serious infections is greatest after the patient has started treatment with a biological drug.
– 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.
NOR-DMARD registry
The doctoral work related to infection risk is based on data from the NORwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) study, a registry of more than 10,000 patients with inflammatory arthritis.
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. In 2017, REK gave permission to link patients in the NOR-DMARD registry to the Cause of Death Registry and the Norwegian Patient Registry, and in 2019, each patient in NOR-DMARD was linked to 10 randomly selected controls who were matched for age, gender and place of residence. Until this work, all research on serious infections and biological treatment has come from data on populations outside Norway, which is not necessarily completely comparable.
Greater risk of infections in rheumatoid arthritis
The first article in this doctoral project was published in 2021 in the Annals of Rheumatic Diseases. It compares the incidence of serious infections between patients with rheumatoid arthritis and psoriatic arthritis receiving treatment with biological drugs from the tumor necrosis factor inhibitor (TNFi) group.
“We found that patients with psoriatic arthritis had a significantly lower risk of serious infections compared to patients with rheumatoid arthritis. We believe this finding is of clinical significance,” she emphasizes.
Equal 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 receiving biological treatment has been 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 biologic drugs have approximately twice the risk of serious infections than the general population, she says.
They found that the risk of serious infection did not change over time, either within each patient population or compared to the general population. Nor did they find any evidence that the risk changes over time within 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 at Diakonhjemmet Hospital and Akershus University Hospital. It was established to map the response to Covid-19 vaccination in patients with inflammatory rheumatoid arthritis and inflammatory bowel disease, who are treated with immunosuppressive drugs.
Data from the Nor-vaC study were used to investigate the duration of antibodies formed after two doses of the coronavirus vaccine, and compared the duration of the antibody response in patients with healthy controls. The work has shown that patients with inflammatory diseases of 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 treated with biological drugs.
