Publications by authors named "Sella Aarrestad Provan"

18 Publications

  • Page 1 of 1

Effects of a mindfulness-based and acceptance-based group programme followed by physical activity for patients with fibromyalgia: a randomised controlled trial.

BMJ Open 2021 06 29;11(6):e046943. Epub 2021 Jun 29.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Norwegian National Advisory Unit on Rehabilitation in Rheumatology, Oslo, Norway.

Introduction: Non-pharmacological approaches are recommended as first-line treatment for patients with fibromyalgia. This randomised controlled trial investigated the effects of a multicomponent rehabilitation programme for patients with recently diagnosed fibromyalgia in primary and secondary healthcare.

Methods: Patients with widespread pain ≥3 months were referred to rheumatologists for diagnostic clarification and assessment of study eligibility. Inclusion criteria were age 20-50 years, engaged in work or studies at present or during the past 2 years, and fibromyalgia diagnosed according to the American College of Rheumatology 2010 criteria. All eligible patients participated in a short patient education programme before inclusion and randomisation. The multicomponent programme, a 10-session mindfulness-based and acceptance-based group programme followed by 12 weeks of physical activity counselling was evaluated in comparison with treatment as usual, that is, no treatment or any other treatment of their choice. The primary outcome was the Patient Global Impression of Change (PGIC). Secondary outcomes were self-reported pain, fatigue, sleep quality, psychological distress, physical activity, health-related quality of life and work ability at 12-month follow-up.

Results: In total, 170 patients were randomised, 1:1, intervention:control. Overall, the multicomponent rehabilitation programme was not more effective than treatment as usual; 13% in the intervention group and 8% in the control group reported clinically relevant improvement in PGIC (p=0.28). No statistically significant between-group differences were found in any disease-related secondary outcomes. There were significant between-group differences in patient's tendency to be mindful (p=0.016) and perceived benefits of exercise (p=0.033) in favour of the intervention group.

Conclusions: A multicomponent rehabilitation programme combining patient education with a mindfulness-based and acceptance-based group programme followed by physical activity counselling was not more effective than patient education and treatment as usual for patients with recently diagnosed fibromyalgia at 12-month follow-up.

Trial Registration Number: BMC Registry (ISRCTN96836577).
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http://dx.doi.org/10.1136/bmjopen-2020-046943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245472PMC
June 2021

Use of video consultations in an outpatient rheumatology clinic.

Tidsskr Nor Laegeforen 2021 05 19;141(8). Epub 2021 May 19.

Background: Due to the COVID-19 pandemic, the implementation of video consultations as an alternative to hospital face-to-face consultations was advanced for persons with rheumatic diseases at Diakonhjemmet Hospital. Video consultations were introduced in March 2020, and this article presents the experiences gained by healthcare professionals and patients.

Material And Method: The data was collected in June 2020 through focus-group interviews with healthcare professionals and through an anonymous online survey of patients who had attended video consultations during a period of three weeks in June 2020.

Results: The data from the focus-group interviews with seven rheumatologists and seven nurses were sorted into main thematic categories: patient, healthcare professional, consultation, and technology. The healthcare professionals felt that video consultations, with some exceptions, were appropriate in the follow-up of patients with rheumatic diseases, and especially for stable patients with no confounding issues. Of the 383 patients who were invited to participate, 139 (36 %) responded to the survey. The patients were largely satisfied with the video consultation, with a median score of 10 (quartiles 8-10) on a numerical rating scale from 0 to 10, however, 32 (27 %) patients considered the lack of clinical examination to be detrimental.

Interpretation: Video consultations are often appropriate in the follow-up of patients with a rheumatic disease.
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http://dx.doi.org/10.4045/tidsskr.20.0882DOI Listing
May 2021

The referral of patients with fibromyalgia to a rheumatological specialist care unit. Is it necessary?

Clin Exp Rheumatol 2021 May-Jun;39 Suppl 130(3):194. Epub 2021 May 13.

Department of Rheumatology, National Resource Centre for Rehabilitation in Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

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July 2021

Trajectories of change in symptom severity in patients with fibromyalgia: exploratory analyses of a randomised controlled trial.

Rheumatol Int 2021 Apr 15;41(4):691-697. Epub 2021 Feb 15.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Norwegian National Advisory Unit on Rehabilitation in Rheumatology, Vinderen, PO Box 23, 0319, Oslo, Norway.

The clinical picture of fibromyalgia (FM) symptoms fluctuates, and the symptom severity varies within and between patients. The current study aimed to identify groups of PDS trajectories and to explore differences in baseline characteristics between the potential groups of trajectories. We included patients from a completed randomised controlled trial, in total 170 patients diagnosed with FM according to the ACR 2010 criteria. The mean age was 40 years, and 94% were women. Symptom severity was assessed by the Polysymptomatic distress scale (PDS) [range 0 (no symptoms) to 31] at four timepoints over 13-18 months. Latent class growth analysis was used to identify patient trajectories based on their response pattern on the PDS. Potential differences in baseline characteristics between the trajectories were compared using appropriate statistical tests. Two distinct PDS trajectories were identified with 110 patients (65%) classified as the "no improvement" group and 60 (35%) as the "some improvement" group. Mean PDS scores at pre-baseline were ≥ 20 in both groups. At 12 months, the groups diverged, mean (SD) PDS score was 14 (3.82) in the "some improvement" group and 21 (4.12) in the "no improvement" group. There were no significant differences in baseline characteristics between the groups of PDS trajectories. We identified one group of FM patients that improved slightly during the study period and one group that not improved. There were no differences in baseline characteristics between the two groups.
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http://dx.doi.org/10.1007/s00296-021-04801-xDOI Listing
April 2021

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors - a Nordic cohort study.

Rheumatology (Oxford) 2021 08;60(8):3656-3668

Bispebjerg and Frederiksberg, The Parker Institute, Copenhagen University Hospital, Hellerup, Denmark.

Objectives: To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA).

Methods: From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001-2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP).

Results: We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9-1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7-1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9-1.1).

Conclusion: In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.
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http://dx.doi.org/10.1093/rheumatology/keaa828DOI Listing
August 2021

Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis.

Rheumatology (Oxford) 2021 08;60(8):3635-3645

Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.

Objectives: To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA.

Methods: All patients with PsA starting secukinumab or a TNFi in 2015-2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+).

Results: We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar.

Conclusion: No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.
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http://dx.doi.org/10.1093/rheumatology/keaa825DOI Listing
August 2021

One-year treatment outcomes of secukinumab versus tumor necrosis factor inhibitors in Spondyloarthritis.

Arthritis Care Res (Hoboken) 2020 Nov 30. Epub 2020 Nov 30.

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Objective: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi), in patients with spondyloarthritis (SpA) using adalimumab as the main comparator.

Methods: Observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis/non-radiographic axial SpA/undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from five Nordic clinical rheumatology registries. Comorbidities and extra-articular manifestations (psoriasis/uveitis/inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios (HR) for treatment discontinuation) and 6-months' response-rates (ASDAS<2.1/BASDAI<40mm, crude/LUNDEX-adjusted, adjusted logistic-regression analyses with odds-ratio(OR)), stratified by line of biological treatment (1 /2 /3 +).

Results: In total, 10,853 treatment courses (842 secukinumab/10,011 TNFi whereof 1,977 adalimumab) were included. The proportion treated with secukinumab during 1 /2 /3 + was 1%/6%/22%). Extra-articular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a one-year retention comparable to adalimumab as 1 or 2 , but poorer as 3 + line of therapy (secukinumab 56% (51%-61%) versus adalimumab 70% (64%-75%)), adjusted HR 1.43 (1.12-1.81). Across treatment lines, secukinumab had poorer estimates for 6-months response rates than adalimumab, statistically significantly so only for 3 + line (adjusted analyses: ASDAS<2.1 OR=0.56 (0.35-0.90), BASDAI<40mm OR=0.62 (0.41-0.95)). Treatment outcomes varied across the five TNFi.

Conclusion: Secukinumab was mainly used in biologically experienced SpA patients. Secukinumab and adalimumab performed similar in patients who had failed a first biological, although with increasing prior biological exposure, adalimumab was superior.
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http://dx.doi.org/10.1002/acr.24523DOI Listing
November 2020

Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy.

RMD Open 2020 Nov;6(3)

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To define fatigue trajectories in patients with rheumatoid arthritis (RA) who initiate biological DMARD (bDMARD) treatment, and explore baseline predictors for a trajectory of continued fatigue.

Methods: One-hundred and eighty-four patients with RA initiating bDMARDs were assessed at 0, 1, 2, 3, 6 and 12 months. Swollen and tender joint counts, patient reported outcomes (PROMs), blood samples and ultrasound examinations were collected at each time point. Fatigue was assessed by the fatigue Numeric Rating Scale (0-10) from the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire. Clinically significant fatigue was predefined as fatigue ≥4. Three trajectories of interest were defined according to level of RAID fatigue: no fatigue (≤3 at 5/6 visits), improved fatigue (≥4 at start, but ≤3 at follow-up) and continued fatigue (≥4 at 5/6 visits). Baseline variables were compared between groups by bivariate analyses, and logistic regression models were used to explore baseline predictors of continued vs improved fatigue.

Results: The majority of patients starting bDMARD therapy followed one of three fatigue trajectories, (no fatigue; n=61, improved; n=33 and continued fatigue; n=53). Patients with continued fatigue were more likely to be anti-citrullinated protein antibody and/or rheumatoid factor positive and had higher baseline PROMs compared to the other groups, while there were no differences between the groups for variables of inflammation including. Patient global, tender joint count and anxiety were predictors for the continued fatigue trajectory.

Discussion: A trajectory of continued fatigue was determined by PROMs and not by inflammatory RA disease activity.
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http://dx.doi.org/10.1136/rmdopen-2020-001372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856128PMC
November 2020

Treatment retention of infliximab and etanercept originators versus their corresponding biosimilars: Nordic collaborative observational study of 2334 biologics naïve patients with spondyloarthritis.

RMD Open 2019 23;5(2):e001079. Epub 2019 Oct 23.

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objective: Although clinical trials support equivalence of originator products and biosimilars for etanercept and infliximab, real-world studies among biologics-naïve patients with spondyloarthritis (SpA) are lacking. The objectives were to compare treatment retention in biologics-naïve patients with SpA starting either the originator product or a biosimilar of infliximab and etanercept, and to explore the baseline characteristics of these patients.

Methods: Patients with SpA (ankylosing spondylitis/non-radiographical axial SpA/undifferentiated SpA), starting infliximab or etanercept as their first-ever biological disease-modifying antirheumatic drug during January 2014-June 2017 were identified in five Nordic biologics-rheumatology registers. Baseline characteristics were retrieved from each registry; comorbidity data were identified through linkage to national health registers. Country-specific data were pooled, and data on infliximab and etanercept were analysed separately. Comparisons of treatment retention between originators and biosimilars were assessed through survival probability curves, retention rates (2 years for infliximab/1 year for etanercept) and Hazard Ratios (HR).

Results: We included 1319 patients starting infliximab (24% originator/76% biosimilar), and 1015 patients starting etanercept (49% originator/51% biosimilar). Baseline characteristics were largely similar for the patients treated with the originators compared with the corresponding biosimilars. Survival probability curves were highly similar for the originator and its biosimilar, as were retention rates: infliximab 2-year retention originator, 44% (95% CI 38% to 50%)/biosimilar, 46% (95% CI: 42% to 51%); and etanercept 1-year retention originator, 66% (95% CI 61% to 70%)/biosimilar, 73% (95% CI 68% to 78%). HRs were not statistically significant.

Conclusion: This observational study of biologics-naïve patients with SpA from five Nordic countries showed similar baseline characteristics and very similar retention rates in patients treated with originators versus biosimilars, for both infliximab and etanercept, indicating comparable effectiveness in clinical practice.
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http://dx.doi.org/10.1136/rmdopen-2019-001079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827791PMC
April 2020

Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register.

Clin Exp Rheumatol 2019 Jan-Feb;37 Suppl 116(1):58-62. Epub 2019 Jan 8.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To examine cross-sectional and longitudinal relationships between fibromyalgia (FM) and rheumatoid arthritis (RA) disease activity.

Methods: 636 patients in the observational Oslo RA register (ORAR) were invited to a clinical examination in 1999. 28-tender and swollen joint counts (TJC, SJC) and 18-tender points were assessed, the RA disease activity score (DAS-28) calculated. Fibromyalgia (FM) was diagnosed according to 1990 (FM-1990) and modified 2011 (mFM-2011) ACR criteria. At the 10-year follow-up patients completed the RA Disease Activity Index (RADAI) and Routine Assessment of Patient Index Data 3 (RAPID-3). Baseline and 10-year RA disease activity were compared across presence/absence of FM. Linear regression models were constructed with 10-year RADAI and RAPID-3 as outcome.

Results: 502 patients participated at baseline data-collection and 10-year data was available in 236. At baseline, mean (SD) age was 59.5 (12.5) years and 87% were female. 9% and 30% had FM-1990 and mFM-2011 respectively. RA-FM patients were predominantly female with higher SJC, TJC, and DAS-28 at baseline. Baseline RA-FM predicted higher levels of RADAI and RAPID-3 at the 10-year follow-up.

Conclusions: RA-FM was associated with significantly higher levels of cross-sectional and longitudinal RA disease activity. FM should be considered in patients with RA not reaching remission.
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May 2019

Effects of a community-based multicomponent rehabilitation programme for patients with fibromyalgia: protocol for a randomised controlled trial.

BMJ Open 2018 06 4;8(6):e021004. Epub 2018 Jun 4.

Department of Rheumatology, National Advisory Unit on Rehabilitation in Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Introduction: People with fibromyalgia (FM) suffer from symptoms such as widespread pain, non-refreshing sleep, fatigue and reduced quality of life. Effects of pharmacological treatment are questionable and non-pharmacological treatments are recommended as first-line therapy. To date the majority of patients with FM in Norway are not offered any targeted treatment. The aim of this randomised controlled trial is to investigate the effects of a community-based multicomponent rehabilitation programme comprising an acceptance-based and mindfulness-based group intervention, the Vitality Training Programme (VTP), followed by tailored physical activity counselling.

Materials And Methods: General practitioners refer potential participants to a rheumatologist in specialist healthcare for diagnostic clarification and assessment of comorbidities. Inclusion criteria are widespread pain/FM ≥3 months, age 20-50 and work participation (minimum part-time) within the last 2 years. The intervention group attends the VTP comprising 10 weekly 4 hour group sessions plus a booster session after 6 months. Thereafter, they receive 12 weeks of individually tailored physical exercise counselled by physiotherapists at community-based Healthy Life Centers. The control group follows treatment as usual. The primary outcome is Patient Global Impression of Change. Secondary outcomes include self-reported pain, fatigue and sleep quality, psychological distress, mindfulness, health-related quality of life, physical activity, work ability and exercise beliefs and habits. To achieve a power of 80% and allow for 10% dropout, 70 participants are needed in each arm. All analyses will be conducted on intention-to-treat bases and measured as differences between groups at 12 months follow-up.

Ethics And Dissemination: The study is approved and granted by the Norwegian South-Eastern Regional Health Authority (reference 2016015). Ethics approval was obtained from Regional Committee for Medical and Health Research Ethics (reference 2015/2447/REK sør-øst A). Results will be submitted to appropriate journals and presented in relevant conferences and social media.

Trial Registration: ISRCTN 96836577.
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http://dx.doi.org/10.1136/bmjopen-2017-021004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988178PMC
June 2018

The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Risk Factors: A 12-Month Longitudinal Study in Rheumatoid Arthritis Patients Treated with Rituximab, Abatacept and Tociliziumab.

PLoS One 2015 26;10(6):e0130709. Epub 2015 Jun 26.

Preventive Cardio-Rheuma clinic, Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To assess whether treatment with one of three novel biological DMARDs; rituximab, abatacept or tocilizumab reduce cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA).

Methods: This is an open, observational and prospective study with visits at baseline, 3, 6, and 12 months. Patients were assigned to receive rituximab, abatacept or tocilizumab according to clinical indications assessed by an independent rheumatologist. Disease activity was quantified by the disease activity score (DAS28) and extensive ultrasonography. CVD risk was assessed by total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), blood pressure and arterial stiffness measurements [pulse wave velocity (PWV) and augmentation index (AIx)]. Within group change in disease activity and CVD risk over 3 months was explored using paired samples bivariate tests. Predictors of change in CVD risk at 3 months were identified in linear regression models. Changes in CVD risk markers over the 12- month follow-up in patients receiving rituximab were assessed by mixed models repeated analyses.

Results: 24 patients on rituximab, 5 on abatacept and 7 on tocilizumab were included. At 3 months PWV was significantly reduced in the tocilizumab group only, but at 12 months rituximab patients showed a significant reduction in PWV. Reduced inflammation at 3 months was associated with increased TC and HDL-c in the entire cohort.

Conclusion: Treatment with tocilizumab and rituximab reduces PWV, a marker of CVD risk, in patients with RA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130709PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482693PMC
April 2016

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

PLoS One 2014 30;9(9):e108688. Epub 2014 Sep 30.

National Advisory Unit on Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; Department of Health Sciences, University of Oslo, Oslo, Norway.

Background: Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA.

Methods: In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals.

Results: Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred.

Conclusion: High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial.

Trial Registration: ClinicalTrials.gov NCT01436942.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108688PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182541PMC
June 2015

The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

Atherosclerosis 2012 Nov 10;225(1):160-5. Epub 2012 Sep 10.

Department of Cardiology B, Oslo University Hospital Ullevaal, Pb 4956 Nydalen, 0424 Oslo, Norway.

Background: Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies.

Methods: Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months.

Results: Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT.

Conclusion: Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.08.033DOI Listing
November 2012

Changes in arterial stiffness during continued infliximab treatment in patients with inflammatory arthropathies.

Fundam Clin Pharmacol 2011 Aug 6;25(4):511-7. Epub 2010 Sep 6.

Division of Cardiology, Oslo University Hospital Aker, 0514 Oslo, Norway.

Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased risk of cardiovascular disease. TNF-α antagonists may improve vascular function in these patients and thus be beneficial with regard to cardiovascular disease. This study evaluated arterial stiffness and disease activity between two infusions with a TNF-α antagonist (infliximab) in patients with inflammatory arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic pulse wave velocity (aPWV), and disease activity were measured in 17 patients with RA, AS, or PsA who had been treated with infliximab for at least 12 months. The patients were examined immediately before their infliximab infusion and thereafter every 10th day until their next infusion scheduled at week 4-8. AIx and aPWV did not change during the period between two infliximab infusions. The patients had a temporary improvement in the general disease activity assessed on visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02) after the infusion. In the group of patients with RA, the Disease Activity Score (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did not alter aortic pulse wave velocity or augmentation index in patients with inflammatory arthropathies who were on long-term infliximab therapy. Reductions in the general disease activity and DAS28 were not reflected in alterations of aortic stiffness or augmentation index.
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http://dx.doi.org/10.1111/j.1472-8206.2010.00872.xDOI Listing
August 2011

Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study.

Hypertension 2010 Feb 28;55(2):333-8. Epub 2009 Dec 28.

Department of Cardiology, Oslo University Hospital Aker, 0514 Oslo, Norway.

The chronic inflammatory state of rheumatoid arthritis and other inflammatory arthropathies, such as ankylosing spondylitis and psoriatic arthritis, contributes to the accelerated atherosclerosis associated with these conditions. This study evaluates the effect of treatment with tumor necrosis factor (TNF)-alpha antagonists on arterial stiffness in patients with inflammatory arthropathies. A total of 60 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and clinical indication for anti-TNF-alpha therapy were included. Thirty-five patients started with anti-TNF-alpha therapy and were compared with a nontreatment group of 25 patients. Aortic stiffness (aortic pulse wave velocity), augmentation index, and disease activity were assessed at baseline and after 3 months. Aortic pulse wave velocity (mean+/-SD) was reduced in the treatment group but not in the control group (-0.50+/-0.78 m/s versus 0.05+/-0.54 m/s, respectively; P=0.002). Concomitantly, C-reactive protein and the disease activity score were reduced in the treatment group (-9.3+/-20.2 mg/L [P<0.001] and -0.74+/-0.91 [P=0.004]). Augmentation index remained unchanged in both groups (0.1+/-7.1% versus -1.0+/-5.8%, respectively; P=0.53). In a multivariate linear regression model, only treatment with TNF-alpha antagonist and change in mean arterial pressure predicted alterations in aortic pulse wave velocity. In summary, anti-TNF-alpha therapy improved aortic stiffness in patients with inflammatory arthropathies. These findings support the idea that anti-inflammatory treatment has a favorable effect on cardiovascular risk in patients with inflammatory arthropathies.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.143982DOI Listing
February 2010

[The many faces of endocarditis].

Tidsskr Nor Laegeforen 2004 Jul;124(13-14):1788-90

Medisinsk avdeling, Lovisenberg Diakonale Sykehus, 0456 Oslo.

Background: Over the past years we have had a relatively large number of patients in our hospital with endocarditis. There has been a variety of clinical presentations, as illustrated by the following case presentations.

Material And Methods: We have conducted a search in our data-based archives of the period from 1.1.1994 to 31.12.2001 and found 25 patients discharged with a diagnosis of endocarditis. We have chosen five case histories that we discuss in the context of published literature.

Results And Interpretation: The signs and symptoms presented include a stroke, severe back pain, a swollen knee, pneumonia and cardiac failure. We especially discuss intravenous drug users and endocarditis of the heart's right side.
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July 2004
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