Early and precise treatment for psoriatic arthritis
What gives patients with psoriatic arthritis the best possible treatment early in the disease? That is the question in NOR-SPRINT, a national clinical study led by Siri Lillegraven at Diakonhjemmet Hospital.
The study investigates whether the use of MRI and ultrasound in follow-up can provide better control of the disease than standard clinical follow-up alone.
The patients participating have recently been diagnosed and are about to start their first disease-modifying treatment. That is, treatment that is intended to slow the disease, not just alleviate symptoms.
– When we started NOR-SPRINT, the main question was whether a better understanding of where patients with psoriatic arthritis have active inflammation would lead to better treatment outcomes, says Lillegraven.
Central to clinical research
Siri Lillegraven is a rheumatologist and head of the Clinical Research Unit at Diakonhjemmet Hospital. She is also deputy head of the research center REMEDY.
For many years, she has worked on large treatment studies in rheumatology and orthopedics. She has also been central to the development of researcher-initiated clinical trials in Norway, i.e. studies that are planned and led by researchers in the health service.
– Interest in randomized controlled trials has grown over time, and it is largely driven by the experiences from ARCTIC, she says.
From everyday clinical practice to clinical studies
When Lillegraven studied medicine in Oslo, her main focus was patient care. Research became an early part of her daily work. She was recruited into the research community at Diakonhjemmet Hospital by Tore K. Kvien. He was one of the first leaders of the rheumatology community at the hospital.
– As a medical student, I was probably most interested in the clinical part of the profession, and it was a lot of coincidence that led me to start research right after my studies, says Lillegraven.
She started with observational studies. These are studies where you follow patients over time and see what happens with treatment, without having a control group.
She later became involved in the ARCTIC study, a large treatment study of patients with early rheumatoid arthritis (RA).
“Through ARCTIC, I learned how much you can learn from a clinical study. The main results influenced clinical practice and thus treatment for a great many patients,” says Lillegraven.
ARCTIC demonstrated that clinical trials can provide answers that change practice. At the same time, the study provided large amounts of data that can be used long after the study is completed. This is one of the reasons why ARCTIC continues to provide new knowledge many years after its inception.
“15 years after the study began, we are still publishing new answers to important clinical questions,” she says.
Important experiences from abroad
During her PhD, Lillegraven spent two years in the United States. She worked in the research group of Daniel H. Solomon in Boston. In the last year, she combined this with studies at the Harvard School of Public Health.
– This stay changed me a lot as a researcher. I learned an incredible amount both from the master's studies and from Solomon , says Lillegraven.
The stay gave her solid training in how clinical studies are structured to provide reliable answers. It involves, among other things, study design, statistics and method. Study design is how you set up the study so that it can actually answer the question you are asking. Method is about how to collect data in a reliable way, and statistics is about how to analyze the data correctly.
The collaboration with the Boston community has continued after she returned to Norway.
The combination of clinical work, methodological expertise and international collaboration has characterized her further work with large randomized controlled trials. A randomized controlled trial means that participants are allocated by drawing lots to different types of follow-up or treatment. In this way, researchers can prevent influence
Why NOR-SPRINT?
Today, Siri Lillegraven leads several clinical research projects. NOR-SPRINT is one of the largest and most comprehensive.
Psoriatic arthritis can present very differently from patient to patient. Some people have mostly joint problems. Others have mostly inflammation where tendons attach to bones (tendon attachments). Many people may also have skin and nail problems, and some have inflammation in the pelvis or back. This makes the disease challenging to assess and treat.
– Psoriatic arthritis can cause very different disease symptoms and be difficult to assess with clinical examination alone, says Lillegraven.
The main question in NOR-SPRINT is whether better knowledge about where the inflammation is located in the body can lead to better treatment. More precise information can make it easier to choose the right medicine for each individual patient. This is important because different medicines can work differently, depending on where the inflammation is located.
– We know that the different medications have varying degrees of effect, depending on where the patient has inflammation, says Lillegraven.
MRI and ultrasound can show inflammation that is not always detected by regular clinical examination. At the same time, such examinations take time and require resources. Therefore, it must be determined whether the benefit is large enough to be used more systematically in follow-up.
“Diagnostic imaging is resource-intensive and time-consuming, both for patients and healthcare personnel. It is important to clarify whether such examinations actually improve patient outcomes,” says Lillegraven.
How the study follows the patients
NOR-SPRINT includes patients who have recently been diagnosed with psoriatic arthritis and are about to start their first disease-modifying treatment. Patients will be followed for two years and have a total of twelve scheduled check-ups.
During the study, patients are examined thoroughly. The team looks at joints, tendon attachments, skin, nails, pelvis and back. If the treatment does not have the desired effect, it is adjusted. The goal is for patients to achieve very good control of the disease as early as possible.
– The patients who participate receive very close and good follow-up, with 12 visits over the course of two years, says Lillegraven.
It is demanding to participate in a study with such close follow-up. At the same time, it can be felt as a sense of security to have a dedicated study team close by in the first years after the disease is discovered.
– We are very grateful to all the patients who participate. It provides a unique opportunity for close follow-up throughout the first two years after the onset of the disease, says Lillegraven.
Two different follow-up strategies
All patients in the study are followed according to a clear treatment plan with clear goals. If the goals are not reached, the treatment should be adjusted stepwise. This is often called a treatment algorithm. In practice, it means a fixed plan for when to assess the effect and when to change treatment.
The difference between the groups is that the doctor in one group also receives structured information from MRI and ultrasound along the way. In this group, the absence of inflammation on ultrasound is also a treatment goal. This means that they not only look at symptoms and findings from regular examinations, but also at whether the ultrasound still shows active inflammation.
Many patients find ultrasound useful because they can see the inflammation themselves.
– We know from the past that many patients find the ultrasound examination motivating. They see where it lights up due to inflammation, and can recognize that the inflammation is disappearing as the treatment takes effect, says Lillegraven.
Ultrasound can also provide the doctor with additional information that can influence the choice of treatment, for example by advancing to a new level of treatment more quickly.
“Additional information from ultrasound may lead to a faster progression to a new level of treatment. It remains to be seen whether this also results in more patients with very good disease control,” says Lillegraven.
A national collaboration
NOR-SPRINT is being conducted at twelve hospitals across the country. This is crucial to recruiting enough patients. It also makes the results more relevant to the entire patient group, because the patients come from different locations and have different backgrounds.
The study is demanding to carry out. It requires close collaboration between rheumatologists, radiologists, laboratories and research personnel at each hospital. It also requires good logistics, i.e. planning and flow in everything from examinations to samples, registrations and appointments.
– NOR-SPRINT would not have been possible without the fantastic efforts of many colleagues in hospitals around Norway. The spirit of hard work in Norwegian rheumatology is impressive, says Lillegraven.
She also points out that such collaborations are an important reason why Norway can conduct large studies that also receive attention beyond the country's borders.
“With relatively rare diagnoses, many studies are impossible to conduct at a single center,” she says.
The patients in the study represent a wide variation in disease presentation and life situation, which strengthens the value of the study and makes the results more relevant to common clinical practice.
– We know that the patients represent the breadth of the patient group, which strengthens the findings, says Lillegraven.
An important part of REMEDY
NOR-SPRINT is a core study in REMEDY, the research center for the treatment of musculoskeletal diseases at Diakonhjemmet Hospital. The fact that the study is part of a center means that it receives support from a larger structure around it. This may include shared expertise in study design and statistics, but also support for coordination and practical implementation.
– REMEDY has given us the opportunity to develop a more solid organization that ties together our studies and raises the quality of the projects, says Lillegraven.
The study is closely linked to the Clinical Trials Unit. This is a unit that provides practical support and expertise in conducting clinical studies. NOR-SPRINT also involves several fellows who work on different parts of the data material. The data material is extensive and allows for multiple analyses over time.
“NOR-SPRINT is collecting extensive data. We believe the study will give rise to a number of analyses and articles on various aspects of psoriatic arthritis,” says Lillegraven.
The center also provides space for academic exchange across projects and disciplines. It strengthens both research and research education, including through REMEDY's Young Researcher Program for younger researchers.
Further significance
Experience from research on rheumatoid arthritis shows that targeted and early treatment can yield very good results. For psoriatic arthritis, there are still several unanswered questions. At the same time, the potential for improvement is great, both in terms of choice of treatment and how patients are followed up.
– Experience from the RA field gives me confidence that there is potential to achieve even better results in psoriatic arthritis, says Lillegraven.
The goal of NOR-SPRINT is to provide knowledge that can contribute to better and more precise treatment, both in Norway and internationally. The results may have implications for future treatment recommendations and for the follow-up of patients in routine clinical practice.
In clinical trials, it is not only positive findings that are valuable. Clear negative findings can also be important, because they can save patients and healthcare systems from interventions that do not provide sufficient benefit.
“We must design the study so that it is interesting with both positive and negative answers. The study must be conducted with such good quality that it provides the clearest answers possible,” says Lillegraven.
For younger clinicians considering research, large treatment trials can be demanding but also very meaningful. They take time, require collaboration, and do not tolerate half-baked solutions. At the same time, they can produce results that impact patient care for years to come.
– Large treatment studies take many years and require a lot of hard work. It is absolutely crucial that you work in a team where you feel comfortable and that you are interested in the research question, says Lillegraven.
