ONGOING PROJECTS

Clinical Research Unit

Introduction

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).[4] 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 [5]. 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[10] 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.[14]

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.

Objectives

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.

The aim of the study is to assess Work Disability, i.e. the extent of sick leave and receipt of a disability pension before and after having been diagnosed with pSS according to the American-European Classification Group criteria.
The severity and duration of flair-up symptoms (temporarily increase in symptoms after treatment) after local steroid injection therapy are unknown. Whether the region treated, severity of inflammation or distribution of medicine plays a role are unclear. The aim of this study is to register flair-up symptoms after steroid injection and relate any symptoms to region, present of inflammation and distribution of medicine seen on ultrasound examination. The results of this study will enable more sufficient information on flair-up symptoms to patients treated with steroid injection therapy

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.

Time plan

The study is enrolling PsA patients until February 2017

The Goback trial is a Randomised controlled trial enrolling 300 participants with difficulty in maintaining physically demanding jobs due to low back pain. The participants will be randomised and stratified according to their age and gender before being allocated in a 1:1 ratio to either control or additional occupational medicine intervention. Both groups will receive conventional treatment for their low back pain during the study. All participants will be thoroughly assessed for causes of low back pain and potential prognostic factors by questionnaires, clinical specialist assessments and magnetic resonance imaging (MRI) scans of the lumbar spine. Primary outcome is the accumulated duration of self-assessed sick leave (in days) due to low back pain during 6 months from baseline. Secondary outcomes include general self-rated back pain, disability and screening for potential prognostic factors: fear avoidance behaviour, disability, health status and degenerative MRI findings. For tertiary purposes selected outcomes will also be assessed after 1 and 2 years from baseline.

Investigators

Henrik Rindel Gudbergsen, Henning Bliddal, Marie Skougaard Nielsen, Lars Erik Kristensen

Funding

Knowledgecentre for telemedicin and The European Commissions Research and Innovation Framework Programme

Summary

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.

Homepage: www.elector.eu

 

Investigators

Henning Bliddal (principal investigator), Signe Rifbjerg-Madsen, Anton W Christensen, Bjarke B Hansen, Mikael Boesen

Sponsor

AbbVie

Summary

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

Summary

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.