Published in 2019

OBJECTIVE: To describe spontaneous changes in time spent physically inactive measured continuously by accelerometry during an 8-week weight loss intervention in overweight/obese individuals with knee osteoarthritis.

METHOD: This study was designed as an observational cohort study including individuals with concomitant overweight/obesity and symptomatic knee osteoarthritis from an osteoarthritis outpatient clinic. Participants completed an 8-week dietary intervention previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of physical inactivity for 24 hours daily during the 8-week intervention period presented as change in the average daily time spent inactive (sitting, reclined or sleeping) from one week prior to intervention to the last week of the intervention.

RESULTS: A total of 124 participants completed the dietary intervention and had valid accelerometer recordings. The mean weight loss was 12.7 kg [95% CI -13.2 to -12.1; P<.0001] after 8 weeks corresponding to a decrease in BMI of 4.3 kg/m2 [95%CI -4.5 to -4.2; P<.0001]. Significant improvements in osteoarthritis symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score) was found across all subscales; for KOOS pain an improvement of 12.8 points [95% CI, 10.6 to 15.0; P<.0001] was observed. No statistically significant change occurred in the average daily time spent inactive from baseline to follow-up (mean change: 8.8 minutes/day [95% CI, -12.1 to 29.7]; P=0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee osteoarthritis symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
ISSN 2151-464X
DOI
Status E-pub ahead of print - 1 mar. 2019

Bibliografisk note

This article is protected by copyright. All rights reserved.

Objectives: A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation.

Methods: One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level.

Results: One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation.

Conclusion: By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 58
Tidsskriftsnummer 1
Sider (fra-til) 110-119
ISSN 1462-0324
DOI
Status Udgivet - 2019

Bibliografisk note

COPECARE

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Wedell-Neergaard, A-S., Lang Lehrskov, L., Christensen, R. H., Legaard, G. E., Dorph, E., Larsen, M. K., Launbo, N., Fagerlind, S. R., Seide, S. K., Nymand, S., Ball, M., Vinum, N., Dahl, C. N., Henneberg, M., Ried-Larsen, M., Nybing, J. D., Christensen, R., Rosenmeier, J. B., Karstoft, K., Pedersen, B. K., Ellingsgaard, H. & Krogh-Madsen, R., 2019, I : Cell Metabolism.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

Originalsprog Engelsk
Tidsskrift Cell Metabolism
ISSN 1550-4131
DOI
Status E-pub ahead of print - 2019

Night work and sick leave during pregnancy: a national register-based within-worker cohort study

Hammer, P. E. C., Garde, A. H., Begtrup, L. M., Flachs, E. M., Hansen, J., Hansen, Å. M., Hougaard, K. S., Kolstad, H. A., Larsen, A. D., Pinborg, A. B., Specht, I. O. & Bonde, J. P., mar. 2019, I : Occupational and Environmental Medicine. 76, 3, s. 163-168 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The aim of our study was to investigate the acute effect of night work during pregnancy on the risk of calling in sick the following day using register-based information and the workers as their own controls.

METHODS: Using the payroll-based national Danish Working Hour Database, including all public hospital employees in Denmark, we identified 9799 pregnant women with ≥1 day shift and ≥1 night shift and ≥1 day of sick leave during the first 32 pregnancy weeks from January 2007 to December 2013. We performed fixed effects logistic regression, that is, within-worker comparisons, of the risk of sick leave of any duration starting within 24 hours after night shifts of different length versus day shifts.

RESULTS: Most of the participants were nurses (64%) or physicians (16%). We found an increased relative risk of sick leave following night shifts compared with day shifts during all pregnancy trimesters. The risk was highest for night shifts lasting >12 hours (OR 1.37, 95% CI 1.15 to 1.63 for nurses; OR 1.87, 95% CI 1.69 to 2.08 for physicians) and among women aged >35 years (OR 1.42, 95% CI 1.24 to 1.63).

CONCLUSION: Among Danish public hospital employees night shifts during pregnancy, especially shifts longer than 12 hours, increased the risk of calling in sick the following day independent of personal factors and time-invariant confounders in all pregnancy trimesters.

Originalsprog Engelsk
Tidsskrift Occupational and Environmental Medicine
Vol/bind 76
Tidsskriftsnummer 3
Sider (fra-til) 163-168
Antal sider 6
ISSN 1351-0711
DOI
Status Udgivet - mar. 2019

Opioid-Induced Reductions in Gait Variability in Healthy Volunteers and Individuals with Knee Osteoarthritis

Henriksen, M., Alkjær, T., Raffalt, P. C., Jørgensen, L., Bartholdy, C., Hansen, S. H. & Bliddal, H., 12 jan. 2019, I : Pain medicine (Malden, Mass.).

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objective: To investigate differences in gait variability induced by two different single-dose opioid formulations and an inert placebo in healthy volunteers and knee osteoarthritis patients.

Design: Experimental, randomized, double-blinded, crossover study of inert placebo (calcium tablets), 50 mg of tapentadol, and 100 mg of tramadol.

Setting: Laboratory setting.

Subjects: Healthy volunteers and knee osteoarthritis patients.

Methods: At three visits, separated by seven days, one tablet was administered per visit according to the randomization code. At each visit, a baseline measurement was done before tablet administration, after which hourly measurements were performed for six hours, yielding a total of seven measurements per visit. Gait variability was measured by three-dimensional gait analysis, recorded during six minutes of continuous treadmill walking at self-selected speed. One hundred seventy gait cycles were identified from detection of clear events of the knee joint angle trajectories. Gait variability was assessed as average standard deviations over a gait cycle of the sacrum displacements and accelerations; sagittal plane ankle, knee, and hip joint angles; step widths; and stride times.

Results: Twenty-four opioid-naïve and neurologically intact participants (12 healthy volunteers and 12 knee osteoarthritis patients) were included and completed the experiment. Tapentadol reduced the variability of sacrum displacements and accelerations compared with placebo and tramadol. There were no differences between experimental conditions regarding the variability in lower-extremity joint angle variability, step widths, or stride times.

Conclusions: In opioid-naïve and neurologically intact individuals, tapentadol seems to reduce movement variability during treadmill walking, compared with placebo and tramadol. This can be interpreted as a loss of adaptability that might increase the risk of falling if the system is perturbed.

Originalsprog Engelsk
Tidsskrift Pain medicine (Malden, Mass.)
ISSN 1526-2375
DOI
Status E-pub ahead of print - 12 jan. 2019

OBJECTIVE: To examine the reporting completeness of exercise-based interventions for knee osteoarthritis (OA) in studies that form the basis of current clinical guidelines, and examine if the clinical benefit (pain and disability) from exercise is associated with the intervention reporting completeness.

DESIGN: Review of clinical OA guidelines METHODS: We searched MEDLINE and EMBASE for guidelines published between 2006 and 2016 including recommendations about exercise for knee OA. The studies used to inform a recommendation were reviewed for exercise reporting completeness. Reporting completeness was evaluated using a 12-item checklist; a combination of the Template for Intervention Description and Replication (TIDieR) and Consensus on Exercise Reporting Template (CERT). Each item was scored 'YES' or 'NO' and summarized as a proportion of interventions with complete descriptions and each intervention's completeness was summarized as the percentage of completely described items. The association between intervention description completeness score and clinical benefits was analyzed with a multilevel meta-regression.

RESULTS: From 10 clinical guidelines, we identified 103 original studies of which 100 were retrievable (including 133 interventions with 6,926 patients). No interventions were completely described on all 12 items (median 33% of items complete; range 17-75%). The meta-regression analysis indicated that poorer reporting was associated with greater effects on pain and no association with effects on disability.

CONCLUSION: The inadequate description of recommended interventions for knee OA is a serious problem that precludes replication of effective interventions in clinical practice. By consequence, the relevance and usability of clinical guideline documents and original study reports are diminished.

PROSPERO: CRD42016039742.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 27
Tidsskriftsnummer 1
Sider (fra-til) 3-22
Antal sider 20
ISSN 1063-4584
DOI
Status Udgivet - jan. 2019

Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies

Alinaghi, F., Calov, M., Kristensen, L. E., Gladman, D. D., Coates, L. C., Jullien, D., Gottlieb, A. B., Gisondi, P., Wu, J. J., Thyssen, J. P. & Egeberg, A., jan. 2019, I : Journal of the American Academy of Dermatology. 80, 1, s. 251-265.e19

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported.

OBJECTIVES: To assess the prevalence and incidence of PsA in patients with psoriasis.

METHODS: Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis.

RESULTS: A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years.

LIMITATIONS: Between-study heterogeneity may have affected the estimates.

CONCLUSIONS: We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.

Originalsprog Engelsk
Tidsskrift Journal of the American Academy of Dermatology
Vol/bind 80
Tidsskriftsnummer 1
Sider (fra-til) 251-265.e19
ISSN 0190-9622
DOI
Status Udgivet - jan. 2019

Response to: 'Mandatory, cost-driven switching from originator etanercept to its biosimilar SB4: possible fallout on non-medical switching' by Cantini and Benucci

Glintborg, B., Loft, A. G., Omerovic, E., Hendricks, O., Linauskas, A., Espesen, J., Danebod, K., Jensen, D. V., Nordin, H., Dalgaard, E. B., Chrysidis, S., Kristensen, S., Raun, J. L., Lindegaard, H., Manilo, N., Jakobsen, S. H., Hansen, I. M. J., Dalsgaard Pedersen, D., Sørensen, I. J., Andersen, L. S., Grydehøj, J., Mehnert, F., Krogh, N. S. & Hetland, M. L., 2019, I : Annals of the Rheumatic Diseases.

Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
ISSN 0003-4967
DOI
Status E-pub ahead of print - 2019

Objectives: To investigate temporal trends in the incidence and prevalence of gout in the adult Danish population.

Methods: Using the nationwide Danish National Patient Registry, we calculated the number of incident gout patients (per 100 000 person-years) within each 1 year period from 1995 to 2015 and the prevalence of gout in 2000 and 2015. Further, we calculated age- and gender-specific incidence rates of gout from 1995 to 2015.

Results: We identified a total of 45 685 incident gout patients (72.9% males) with a mean age of 65 years (s.d. 16) at diagnosis. In both genders, an increase in age-standardized incidence rates was observed from 32.3/100 000 (95% CI 30.7, 33.9) in 1995 to 57.5/100 000 (95% CI 55.6, 59.5) in 2015 (P < 0.001). Similar trends were observed for 8950 cases diagnosed in rheumatology departments. We likewise observed an increase in the prevalence of gout from 0.29% (95% CI 0.29, 0.30) in 2000 to 0.68% (95% CI 0.68, 0.69) in 2015.

Conclusions: The annual incidence rate of gout increased by almost 80% in Denmark between 1995 and 2015. The prevalence increased by nearly 130% between 2000 and 2015. Reasons for this are unknown but may include an increase in risk factors (e.g. obesity, diabetes mellitus), longer life expectancy and increased awareness of the disease among patients and/or health professionals.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
ISSN 1462-0324
DOI
Status E-pub ahead of print - 2019

Published in 2018

2018 update of the EULAR recommendations for the management of Behçet's syndrome

Hatemi, G., Christensen, R., Bang, D., Bodaghi, B., Celik, A. F., Fortune, F., Gaudric, J., Gul, A., Kötter, I., Leccese, P., Mahr, A., Moots, R., Ozguler, Y., Richter, J., Saadoun, D., Salvarani, C., Scuderi, F., Sfikakis, P. P., Siva, A., Stanford, M., Tugal-Tutkun, I., West, R., Yurdakul, S., Olivieri, I. & Yazici, H., jun. 2018, I : Annals of the Rheumatic Diseases. 77, 6, s. 808-818 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer 6
Sider (fra-til) 808-818
Antal sider 11
ISSN 0003-4967
DOI
Status Udgivet - jun. 2018

A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process

HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC), sep. 2018, I : British Journal of Dermatology. 179, 3, s. 642-650 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome-reporting bias and limits the ability to synthesize evidence.

OBJECTIVES: To achieve global multistakeholder consensus on a core outcome set (COS) of domains regarding what to measure in clinical trials for HS.

METHODS: Six stakeholder groups participated in a Delphi process that included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final COS. The aim was for a 1 : 1 ratio of patients to healthcare professionals (HCPs).

RESULTS: A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process, which yielded a final COS that included five domains: pain, physical signs, HS-specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by HCPs but is recommended for the core domain set.

CONCLUSIONS: Routine adoption of the COS in future HS trials should ensure that core outcomes of importance to both patients and HCPs are collected.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 179
Tidsskriftsnummer 3
Sider (fra-til) 642-650
Antal sider 9
ISSN 0007-0963
DOI
Status Udgivet - sep. 2018

A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A GRAPPA-OMERACT initiative

Højgaard, P., Klokker, L., Orbai, A-M., Holmsted, K., Bartels, E. M., Leung, Y. Y., Goel, N., de Wit, M., Gladman, D. D., Mease, P., Dreyer, L., Kristensen, L. E., FitzGerald, O., Tillett, W., Gossec, L., Helliwell, P., Strand, V., Ogdie, A., Terwee, C. B. & Christensen, R., 2018, I : Seminars in Arthritis and Rheumatism. 47, 5, s. 654-665

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Tidsskriftsnummer 5
Sider (fra-til) 654-665
ISSN 0049-0172
DOI
Status Udgivet - 2018

Bibliografisk note

COPECARE

Acute sensory and motor response to 45-s heavy isometric holds for the plantar flexors in patients with Achilles tendinopathy

O'Neill, S., Radia, J., Bird, K., Rathleff, M. S., Bandholm, T., Jorgensen, M. & Thorborg, K. 1 aug. 2018 I : Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: The purpose of this study was to explore the immediate effects of heavy isometric plantar flexor exercise on sensory output (pain during a functional task and mechanical pain sensitivity) and motor output (plantar flexor torque) in individuals with Achilles tendinopathy.

METHODS: Sixteen subjects with Achilles tendinopathy participated in the study, mean (SD) age 48.6 (8.9) years and Victorian institute assessment-Achilles (VISA-A) score 61.3 (23.0). Sensory testing assessing pain during a functional task, mechanical pain sensitivity and motor output, and plantar flexor peak torque was completed prior to the intervention. All subjects completed a 45-s heavy isometric plantar flexor contraction and were then re-tested using the same sensory and motor tests. Motor output was assessed using isokinetic dynamometry at speeds previously identified as of interest in subjects with Achilles tendinopathy.

RESULTS: Only 9 of the 16 subjects experienced pain during a functional task, self-reported pain was 4.2 (1.9) numerical rating scale (NRS) pre-intervention and 4.9 (3.2) NRS postintervention (n.s.). Mechanical pressure sensitivity was 446.5 (± 248.5) g/mm2 pre-intervention and 411.8 (± 211.8) g/mm2 post-intervention (n.s.). Mean concentric plantar flexor torque at 90 and 225°/s was 47.1 (14.5) and 33.6 (11.6) Nm, respectively, pre-intervention and 53.0 (18.5) and 33.4 (6.6) Nm post-intervention (p = 0.039 and n.s.). Eccentric torque at 90°/s was 98.5 (34.2) Nm preintervention versus 106.0 (41.4) Nm post-intervention (n.s.).

CONCLUSION: In this exploratory study, patients with Achilles tendinopathy had a varied sensory and motor output response to heavy isometric contractions. Using the recommended approach of heavy 45-s isometric contractions did not offer a meaningful acute benefit for sensory or motor output for subjects with Achilles tendinopathy. Based on this study, heavy 45-s isometric contractions cannot be recommended for immediate pain relief or improved motor output for patients with Achilles tendinopathy.

LEVEL OF EVIDENCE: IV, prospective cohort study.

Originalsprog Engelsk
Tidsskrift Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
ISSN 0942-2056
DOI
Status E-pub ahead of print - 1 aug. 2018
Originalsprog Engelsk
Artikelnummer P19
Tidsskrift Endocrine Abstracts
Vol/bind 56
ISSN 1479-6848
DOI
Status Udgivet - 2018

An MRI guided treat-to-target strategy in rheumatoid arthritis patients in clinical remission improved MRI inflammation but not damage progression – Results from the IMAGINE-RA randomised controlled trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B., Glinatsi, D. E., Hetland, M. L., Ørnbjerg, L. M., Møller, J. M., Boesen, M., Christensen, R. D. K., Stengaard-Pedersen, K., Madsen, O. R., Jensen, B., Villadsen, J., Hauge, E. M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M. R., Lindegaard, H., Nielsen, S. M., Bliddal, H., Krogh, N., Ellingsen, T., Nielsen, A. H., Balding, L., Jurik, A. G., Thomsen, H. & Østergaard, M., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 126 1 s., OP0149.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer OP0149
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer Suppl. 2
Sider (fra-til) 126
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2018

An MRI Guided Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission Improved MRI Inflammation but Not Damage Progression – Results from the Imagine-RA Randomized Controlled Trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B. J., Glinatsi, D. E., Hetland, M. L., Ørnbjerg, L. M., Møller, J. M., Boesen, M., Christensen, R. D. K., Stengaard-Petersen, K., Madsen, O. R., Jensen, B., Villadsen, J. A., Hauge, E-M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M. R., Lindegaard, H., Nielsen, S. M., Bliddal, H., Krogh, N. S., Ellingsen, T., Nielsen, A., Balding, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., 2018, I : Arthritis & Rheumatology. 70, S9, 2 s., 867.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 867
Tidsskrift Arthritis & Rheumatology
Vol/bind 70
Tidsskriftsnummer S9
Antal sider 2
ISSN 1537-2960
Status Udgivet - 2018

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

Almholt, K., Hebsgaard, J. B., Nansen, A., Andersson, C., Pass, J., Rønø, B., Thygesen, P., Pelzer, H., Loftager, M., Lund, I. K., Høyer-Hansen, G., Frisch, T., Jensen, C. H., Otte, K. S., Søe, N. H., Bartels, E. M., Andersen, M., Bliddal, H. & Usher, P. A., 1 feb. 2018, I : Journal of immunology (Baltimore, Md. : 1950). 200, 3, s. 957-965

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

Originalsprog Engelsk
Tidsskrift Journal of immunology (Baltimore, Md. : 1950)
Vol/bind 200
Tidsskriftsnummer 3
Sider (fra-til) 957-965
ISSN 0022-1767
DOI
Status Udgivet - 1 feb. 2018

Knee osteoarthritis (KOA) is one of the most common causes of physical disability in the elderly population. With an increasing ageing and obese population, the prevalence of KOA is expected to rise substantially. The needs for a better understanding of the disease and tools that can predict the course of the disease, for example following treatment, are therefore imperative. 

Inflammation has over the last years been recognised as an important factor for both the symptomatology and disease course in KOA. Synovitis, inflammation of the synovium, is the hallmark of intra-articular inflammation and has been associated with pain, symptoms and disease progression. Synovitis can be visualised on conventional static MRI. However, the addition of a dynamic contrast-enhanced (DCE) MRI-sequence enables the assessment of the synovium both in regards of its morphology and perfusion. Studies in both KOA and rheumatoid arthritis have shown that DCE-MRI measures of synovitis are more sensitive than conventional static MRI in regards of microscopic synovitis and patient-reported outcome measures (PROMs).

 The aims of this PhD project were to characterise synovitis in KOA with conventional static and DCE MRI in regards of histology (study I), its association with PROMs (studies II-III) and changes following a symptoms-improving intervention (study III). We found that DCE-MRI-measures of synovitis seem to be superior to conventional static MRI in their association with histological synovitis (study I) and pain (study II) in a cross-sectional setting. However, the use of DCE-MRI over conventional static CE-MRI cannot be justified when assessing the long-term changes in synovitis following an intervention with intra-articular corticosteroids/placebo and exercise (study III). 

Evidence is mounting that KOA is constituted of different phenotypes. There is an urgent need to define these in order to improve and individualise treatment and management. It is essential to gain a better understanding of the different pro-cesses taking place in KOA, on an individual level and in the different stages of the disease. DCE-MRI may very well be a useful tool in facing these challenges especially in regards of the role of perfusion and inflammation in KOA and osteoarthri-tis in general.

Originalsprog Engelsk
Tidsskrift Danish Medical Journal
Vol/bind 65
Tidsskriftsnummer 4
ISSN 1603-9629
Status Udgivet - apr. 2018

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study

Andersen, M., Boesen, M., Ellegaard, K., Söderström, K., Søe, N. H., Spee, P., Mørch, U. G. W., Torp-Pedersen, S., Bartels, E. M., Danneskiold-Samsøe, B., Karlsson, L. & Bliddal, H., 2018, I : PLoS One. 13, 5, s. e0197001

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline.

METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.

RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.

CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 13
Tidsskriftsnummer 5
Sider (fra-til) e0197001
ISSN 1932-6203
DOI
Status Udgivet - 2018

Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis

Hawley, S., Cordtz, R., Dreyer, L., Edwards, C. J., Arden, N. K., Delmestri, A., Silman, A., Cooper, C., Judge, A. & Prieto-Alhambra, D. 2018 I : Seminars in Arthritis and Rheumatism. 47, 5, s. 605-610

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales.

METHODS: Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend.

RESULTS: We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates.

CONCLUSIONS: Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Tidsskriftsnummer 5
Sider (fra-til) 605-610
ISSN 0049-0172
DOI
Status Udgivet - 2018

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