Clinical Research Unit
SECTION 1: ADMINISTRATIVE INFORMATION
Effect of a liraglutide-based weiht-loss intervention on radiographic knee osteoarthritis progression in patients with overweight: a secondary analysis of a randomized controlled trial.
Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease with heterogenous symptoms that affect a variety of structures in a distinct individual way. Symptoms experienced by the individual patient might include clinical manifestations involving skin, joints, entheses, nails, and/or other connective tissues. Nonetheless, patients diagnosed with PsA suffer from the alleged same disease they experience a diverse range of symptoms and manifestations which respond very differently to available treatments.
Current treatment strategies include first line treatment with disease modifying anti-rheumatic drugs (DMARDs) with little and/or unsatisfactory effect in PsA (1-3) . Biological treatment of PsA include Tumor Necrosis Factor α (TNFα) inhibitors and Interleukin 17 (IL-17) inhibitors (4). Nevertheless, 20-30% of PsA patients fail to respond to available biological agents (5, 6) which might be explained by different response to drugs due to different patient- and/or disease specific characteristics as implied in one study of survival rates of TNF inhibitor in patients with two different PsA phenotypes (7). This is demonstrating the importance in comparing the immune pathological findings with patient- and disease specific characteristics and treatment response.
T-cell differentiation with development of the T-cell into specific T-cell phenotypes is believed to play an important role in the immune pathological pathway of PsA (8, 9). While T helper cell type (th) 1 and th17 cells are believed to play a part in development of adaptive autoimmune response and tissue damage in PsA, recent knowledge further implement an innate autoinflammatory response (10). Nevertheless, the association between different T-cell phenotypes in PsA remain unclear and current evidence has also been associating several additional cell types of both innate and adaptive immunity with the developing inflammatory response leading to PsA (8).
Studies on the effect of treatment on human T cell phenotypes is limited. In PsO, TNFα inhibition has shown decreased levels of circulating Th17 cell and reduced Th1 activity (11, 12), while one study showed increased numbers of circulating Th17 cells in patients with inflammatory arthritis (including PsA) during TNFα inhibitor treatment (13). Studies regarding effect of treatment on immune cell phenotypes, including both methotrexate (MTX), IL17 inihibitors (IL17i) and TNFα inhibitors (TNFi), are needed in order to further understand immune pathological mechanisms of PsA. Furthermore, it is important to investigate immune cell phenotypes and associations with different clinical PsA phenotype that might provide knowledge on how to choose between treatments to ensure optimal effect on various symptoms.
Weight loss as treatment for gout in patients with concomitant obesity: Protocol for a proof-of-concept randomised, non-blinded, parallel-group trial
Psoriatic arthritis (PsA) is a chronic inflammatory disorder characterized by peripheral joint inflammation, nail involvement, enthesitis, tenosynovitis and dactylitis, as well as increased risk of extra-articular manifestations (psoriasis, uveitis, urethritis, inflammatory bowel disease) and other co-morbidities, especially metabolic, cardiovascular and psychological disorders.[1-3] During the last decades, the treatment of PsA has improved dramatically, mainly due to the introduction of biological disease modifying anti-rheumatic drugs (bDMARDs) such as tumor necrosis factor inhibitors (TNFIs). TNFIs are expensive and may cause serious side effects why prescription of these drugs in Denmark is reserved for patients with ongoing, severe disease who are unresponsive to treatment with conventional synthethic (cs)DMARDs. Response to TNFIs is however insufficient in approximately 50% of patients in routine care . Predictors of outcomes to TNFI therapy have been suggested to include clinical, laboratory, lifestyle-related and demographic factors although the overall evidence for specific response modifiers is limited.[6-9] A better understanding of the complex interaction between genetic/biologic and environmental factors is necessary to elaborate risk profiles and personalized treatment recommendations. A gender bias in the prevalence and pathophysiology[11-13] in PsA has been suggested by recent literature and we hypothesize that gender could also play a central prognostic role in relation to therapeutic outcomes. Although some studies already support this idea, the results have been diverging emphasizing the need to further explore this research question.
Project supervisor: Signe Rifbjerg-Madsen1,2, MD, PhD Student
Clinically responsible physician: Kirstine Amris1,2, Consultant, MD
Senior Biostatistician: Robin Christensen1, BSc, MSc, PhD
Other collaborators: Bente Danneskiold-Samsøe1, Professor, MD, DMSc Henning Bliddal1, Professor, MD, DMSc Anton T. Christensen1,2 , MD, PhD Student Christian Cato Holm1, MSc,
Database manager DANBIO collaborators: Merete Lund Hetland3 Professor, MD, PhD, DMSc Niels Steen Krogh4, MSc, Database manager Affiliations:
Association between surrogate markers of inflammation as detected by ultrasound and results of an intensive weight loss program obese patients with knee osteoarthritis: a prospective cohort study based on the CAROT Trial v. 2.0 (january 17, 2017)
~Fatigue defined as being sustained physical tiredness, mental exhaustion, and a lack of energy is a
well-known symptom of many chronic diseases (1;2) and often a crucial aspect in the management of
chronic diseases (3).
It is a common symptom in patients with psoriatic arthritis (PsA) and for patients impacted by fatigue
it is deemed to be one of the most significant symptoms (2;4;5). Moreover, patients with PsA are
characterised by having a decreased quality of life compared to other patient groups and often fatigue
is reported to be the limiting factor in terms of participation in daily activities (6;7).
Though fatigue is considered an important outcome measure for PsA patients this outcome is not yet
embedded completely in clinical practice or in the scientific thinking within this disease-area. Fatigue
is rarely reported by clinicians and studies on patient-reported fatigue outcomes are limited (2;8)
However, the focus on fatigue is increasing. Recent studies describe the association between fatigue in
PsA and pain, female gender, physical disability, medication status, psychological distress,
longstanding sick leave, and loss of work ability (3;5). Furthermore, biological agents are shown to
have a positive impact and beneficial effect on patients suffering from fatigue suggesting a link
between fatigue and inflammatory signalling (9;10). Moreover, fatigue was only recently added in the
GRAPPA-OMERACT’s core set of outcome measures for PsA (2;4)
To our knowledge the association between underlying components of fatigue in relation to PsA has
never been explored on basis of data from large cohort studies. The aim of the study is to describe the
degree of fatigue in patients with PsA in a nationwide study, and to explore important associated
components of fatigue.
The objective of this study is to investigate whether PsA comorbidities, assessed by use of the CCI, are associated with disease activity, treatment response and treatment adherence in patients with PsA treated with their first TNFi. Furthermore, we will assess whether depression and/or anxiety have an influence on the treatment effect and adherence.
Persistent pain is a common symptom in patients with psoriatic arthritis (PsA) and may be caused by ongoing inflammation in joints, entheses and tendons. In some cases, ongoing pain may be due to “sensitization” of nerve cells involved in pain processing, which leads to increased pain perception even in the absence of disease activity. We aim to study pain mechanisms in relation to disease activity measured by clinical examination and ultrasound (US) of several musculoskeletal structures, in patients with PsA. Further, we intend to clarify if assessment of pain mechanisms and US are valuable tools to predict response to anti-inflammatory treatment in PsA.
The study is enrolling PsA patients until February 2017
Henrik Rindel Gudbergsen, Henning Bliddal, Marie Skougaard Nielsen, Lars Erik Kristensen
Knowledgecentre for telemedicin and The European Commissions Research and Innovation Framework Programme
The ELECTOR project aims to develop a web-based platform for home-based monitoring of self-reliant patients with rheumatoid arthritis. The solution will encompass point-of-care devices for the measurement of biochemistry at home and a web-based user interface for capturing patient reported outcomes.
The proposed eHealth platform will encompass point-of-care devices used for measuring biochemistry at home and a web-based graphical user interface for communication, knowledge transfer and for the reporting of questionnaires as well as joint assessments. This solution will constitute a reliable, safe and straightforward method for obtaining self-assessments and facilitate easy, rapid and customizable access to health care assistance at times of need.
The end result is a platform that will provide an integrated and direct collection of data into patient notes in the set-up of an e-Health outpatient clinic for citizens with rheumatoid arthritis. This solution will constitute a reliable, safe and straightforward method for obtaining self-assessments and facilitate easy and rapid access to health care assistance at times of need for the individual patient.
Henning Bliddal (principal investigator), Signe Rifbjerg-Madsen, Anton W Christensen, Bjarke B Hansen, Mikael Boesen
Joints with osteoarthritis are characterized by inflammation in many instances. The inflammation may cause tissue damage, while also be a major contributor to the clinical problems with the joint, especially pain. Over the years, joints with inflammation have been treated with injection of glucocorticosteroids to deal with this problem. This treatment, however, is not a lasting solution to the inflammation and there is a demand for other medications with anti-inflammatory properties. In this project, subjects with defined signs of inflammation in the osteoarthritic knee joint will be enrolled in a RCT. Test drug is acting on Il-1 and the effect will be followed both clinically and by imaging, in this case dynamic contrast enhanced MRI. The randomization has 4 arms with one placebo and three active, with a distribution 1:2:2:2. The test medication is given as injection every 2 weeks for a year.
Principal investigator: Eva Ejlersen Wæhrens(EEW), OT, PhD; Study manager/ Facility coordinator: Alice Røpke (AR), OT; Co-Investigator: Karen Ellegaard(KE), PT, PhD; Biostatistician: Robin ChristensenRC), M.Sc., PhD; Co-Investigator: Marius Henriksen(MH), PT, PhD; Co-Investigator/ Medically responsible: Signe Rifbjerg-Madsen (SRM), MD; Co-Investigator: Henning Bliddal(HB), MD, D.M.Sc. Co-Investigator/: Bente Danneskiold-Samsøe(BDS), MD, D.M.Sc
Female patients with rheumatoid arthritis will be randomized to hand exercise therapy as an add on to a compensatory intervention program focused on joint protection, assistive devices and alternative methods of doing. Hand exercise effects on self-reported and observed ADL ability, disease activity and grip strength will be assessed. Furthermore, the perfusion of the synovial tissue as indicator of inflammation in the wrist and finger joints will be determined by means of US Doppler.