Merete Lund Hetland's research while affiliated with IT University of Copenhagen and other places

Publications (448)

Article
Objectives: To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods: We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through eff...
Article
Objective: It remains disputed how much the risk of Staphylococcus aureus bacteraemia (SAB) is increased in patients with rheumatoid arthritis (RA), and the extent to which orthopaedic implants explain the risk. We assessed SAB incidence rates (IRs) and incidence rate ratios (IRRs), comparing RA patients with a general population cohort (GPC) and...
Article
Objectives To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator. Methods Observational coho...
Article
Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in combination with a tumour necrosis factor inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi a...
Article
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Biopharmaceuticals have revolutionized the treatment of many diseases such as diabetes, cancer, and autoimmune disorders. These complex entities provide unique advantages like high specificity towards their target. Unfortunately, biopharmaceuticals are also prone to elicit undesired immunogenic responses (immunogenicity), compromising treatment eff...
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Objective The programmed death-1 (PD-1) pathway is essential for maintaining self-tolerance and plays an important role in autoimmunity, including rheumatoid arthritis (RA). Here, we investigated how membrane-bound and soluble (s)PD-1 influence bone homeostasis during chronic inflammation, exemplified in RA. Methods Bone mineral density and bone m...
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Objectives To investigate whether patient-reported outcomes vary across countries and are influenced by cultural/contextual factors. Specifically, we aimed to assess inter-country differences in tender joint count (TJC), pain and patient’s global health assessment (PGA), and their impact on disease activity (DAS28-CRP) in rheumatoid arthritis (RA)...
Article
Objectives: To develop and validate in real-world patients a conversion algorithm from the Multidimensionel Health Assessment Questionnaire physical function scale (MDHAQ) to the Stanford HAQ disability index physical function scale (HAQ) score. Methods: From the DANBIO registry, 13 391 patients with rheumatoid arthritis (RA, n = 8,983), psoriat...
Article
Objective Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. Method Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 wa...
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Background/Purpose: In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more...
Article
Objectives: In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of firs...
Article
Objectives: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating tumour necrosis factor inhibitor (TNFi) treatment. Methods: Prospectively collected data on bio-naïve axSpA and PsA patients from routine car...
Article
Objectives: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating tumour necrosis factor inhibitor (TNFi) treatment. Methods: Prospectively collected data on bio-naïve axSpA and PsA patients from routine care i...
Article
Objectives To explore the association of maternal rheumatoid arthritis (RA) to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (SRQ) and Den...
Article
Objective : To explore the registration, pattern and burden of clinical enthesitis among routine-care patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in the Danish nationwide DANBIO registry. Methods : In patients with PsA and axSpA in DANBIO, prospectively registered data from 2010-2020 on clinical entheseal assessment...
Article
Objectives: In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels...
Article
Objective A randomized controlled trial [Joint Resources – Sedentary Behaviour (JR-SB) intervention] aimed to reduce sedentary behaviour and increase light-intensity physical activity in patients with rheumatoid arthritis (RA) through motivational counselling and text messages. Since a large proportion of invited patients declined to participate, t...
Article
Objectives: It remains challenging to identify rheumatoid arthritis (RA) patients at a high risk of joint destruction. The C-X-C motif chemokine 13 (CXCL13) has previously been suggested as a marker of disease activity in RA. Here, we investigate the potential of plasma CXCL13 as a marker of long-term radiographic status and progression. Methods:...
Article
Objectives: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered tumor necrosis factor inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining...
Article
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We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to...
Article
Objectives: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. Method: One-hundred patients with established RA,...
Article
Purpose: The “Joint Resources – Sedentary Behavior Study” (JR-SB) revealed significant behavioral and cardio-metabolic effects of reducing daily sedentary behavior replaced by light-intensity physical activity in patients with rheumatoid arthritis. This study explores the participant perception and experiences of the intervention and impact on the...
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Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methot...
Article
Objective : To determine how best to incorporate the patient perspective into rheumatoid arthritis remission criteria. Methods : At OMERACT 2020, several studies, including a longitudinal multi-centre study testing the validity of adding patient-valued domains to the ACR/EULAR criteria, were presented and discussed by the virtual Special Interest...
Article
Objectives To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease. Furthermore, to explore characteristics of patients with/without physical consultations in the clinic, and impact of early versus establishe...
Article
Background Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bio-naïve axial spondyloarthritis (axSpA) patients treated in routine care is limited. Objectives To investigate secular trends in baseline characteristics and retention, remission and response rates in axSpA patients initia...
Article
Background In clinical practice, some patients with axial spondyloarthritis (axSpA) fail several consecutive biological treatments (bDMARDs). How this group of ”refractory” patients should best be defined, how common they are, and what their characteristics are, is poorly understood. Objectives To explore the point prevalence of bDMARD refractory...
Article
Background Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bionaïve psoriatic arthritis (PsA) patients treated in routine care is limited. Objectives To investigate secular trends in baseline characteristics and retention, remission and response rates in PsA patients initiating a fi...
Article
Background Busy rheumatologists may assess disease activity and risk for radiographic progression (RP) in RA with informal, qualitative versions of evaluator and/or patient global assessments (EGA and PGA). RA patient care may be improved by having a convenient, objective disease activity measure that predicts risk for RP more accurately than EGA o...
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Background During the COVID-19 pandemic, widespread changes in how we work have been observed. Working from home is not an option for everyone. At work it may be difficult to keep social distance, which may lead to fear and anxiety of being infected with SARS-CoV-19 or of spreading the virus. Objectives To explore frequency of anxiety and concerns...
Article
Background Interstitial lung disease (ILD) is an established extra-articular manifestation of rheumatoid arthritis (RA). Few studies have investigated the prevalence of ILD in patients with psoriatic arthritis (PsA). Methotrexate (MTX) is frequently used in the treatment of both RA and PsA and has been suggested to be a risk factor for the developm...
Conference Paper
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Background The interplay between genetics and drug response in rheumatoid arthritis (RA) has shown that response to biologics varies between individuals and that a large proportion of patients show no clinical improvement (Plenge and Bridges, 2011). Despite the disappointing scenario, to date, only a few genetic markers have been consistently ident...
Article
Background Rheumatoid Arthritis (RA) is associated with increased cardiovascular co-morbidity including acute coronary syndrome (ACS), partly due to effects of systemic inflammation. Disease-modifying anti-rheumatic drugs (DMARDs) may reduce RA disease activity, but act through several pathways and may themselves have an impact on cardiovascular ri...
Article
Background Women with rheumatoid arthritis (RA) are at increased risks of adverse pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA). However, the link between RA disease activity, type and timing of anti-rheumatic treatment, and the risk of these outcomes remains unclear. Objectives To explore the associations...
Article
Background The COVID-19 pandemic has caused lockdown, reduced access to face-to-face consultations, anxiety about taking immunosuppressive agents and self-isolation ¹ which potentially impact rheumatic disease control negatively. However, changes in behavior including self-protection strategies during the ongoing pandemic and impact on rheumatic di...
Article
Objectives: In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthr...
Article
Objective To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological disease-modifying anti-rheumatic drugs (bDMARDs) at 2-year follow-up in rheumatoid arthritis (RA) patients in sustained remission. Methods Patients in sustained remission (DAS28-CRP≤2.6) and no radiographic progression the prev...
Article
Objective In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rit...
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Background Subclinical synovitis by ultrasound is a frequent finding in rheumatoid arthritis (RA) patients in remission and has been shown to be related to erosive progression, risk of flare and unsuccessful drug tapering, but it has not been investigated how a DAS28 T2T-steered strategy in routine care affects the presence of subclinical synovitis...
Article
Objectives Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with the general population and, second, to develop a simple clinical pred...
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Background: To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. Methods: Twelve women with RA and five healthy women were included in...
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Objective There is a lack of real‐life studies on IL‐17 inhibition in psoriatic arthritis (PsA). We assessed real‐life 6‐/12‐month effectiveness (i.e. retention, remission, low‐disease‐activity [LDA] and response rates) of the IL‐17 inhibitor secukinumab in PsA patients overall, and across 1) number of prior biologic/targeted synthetic Disease‐Modi...
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Background: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings wi...
Article
To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received me...
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Aims In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients...
Article
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...
Article
Objective To assess whether gene expression signatures associated with rheumatoid arthritis (RA) before pregnancy differ between women who improve or worsen during pregnancy, and determine whether these expression signatures are altered during pregnancy when RA improves or worsens. Methods Clinical data and blood samples were collected before preg...
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Objective To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. Design Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. Setting Twenty nine rheumatology departments in Swed...
Article
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 a...
Article
Objectives: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. Methods: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs...
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Background: Human and animal studies support the involvement of diet in the development of CID -chronic inflammatory diseases such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis. Objective: This cohort study aimed to investigate the association between intake of fibre, red and processed m...
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Objectives: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries. Methods: Real-life data from 13 Eu...
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Objectives: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. Methods: We...
Article
Objectives: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. Methods: PsA patients registered in the Nordic rheumatology registries initiating any...
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Objective: To compare joint inflammation seen by whole-body magnetic resonance imaging (WBMRI), with “whole-body” ultrasound and clinical assessments, in patients with active rheumatoid arthritis (RA) before and during tumor necrosis factor-inhibitor (TNF-I, adalimumab) treatment. Methods: In 18 patients with RA, clinical assessment for joint tende...
Article
Background Axial spondylarthritis (axSpA) patients treated with a tumour necrosis factor inhibitor (TNFi) may receive a concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), although the value of combination therapy remains unclear. Objectives Describe the proportion and phenotype of patients with axSpA initiating the...
Article
Background Smoking is a known risk factor for rheumatoid arthritis (RA). It is largely unknown whether smoking has any impact on disease activity and treatment outcomes (e.g. achieving remission on methotrexate and time to first biological disease modifying anti-rheumatic treatments (bDMARD)) in early RA with a modern treat-to-target strategy. Obj...
Article
Background Staphylococcus aureus is a frequent cause of bacteremia (SAB) associated with high mortality and morbidity. Patients with rheumatoid arthritis (RA) are at increased risk of septic arthritis and prosthetic joint infection with S. aureus . Objectives To assess the incidence rate (IR) of first-time SAB in patients with RA and to estimate t...
Article
Background To determine the real-life 6- and 12-month secukinumab effectiveness in Europe overall, as well as stratified by prior biologic disease-modifying anti-rheumatic drug (bDMARD)/targeted synthetic (ts)DMARD use. Objectives Real-life data from axSpA patients treated with secukinumab from 13 countries in the European Spondyloarthritis (EuroS...
Article
Background The effect of different treatment escalations on MRI inflammation in rheumatoid arthritis (RA) patients following an MRI treat-to-target (T2T) strategy has not previously been investigated. Objectives To compare the effect of different treatment escalations on MRI inflammation, physical function and disease activity in RA patients in cl...
Article
Background Achieving remission according to stringent criteria such as Simplified Disease Activity Index (SDAI) and ACR/EULAR Boolean remission is associated with a better long-term outcome in patients with RA ¹ . Possible predictors of achieving stringent remission in patients in clinical remission, following targeted treatment strategies, have no...
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Background The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established. Objectives The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess...
Article
Background Low vitamin D levels are common in Rheumatoid Arthritis (RA) ¹ , and possibly associated with disease course, ² but data on vitamin D levels during long-term disease course has not been reported previously. Objectives To describe vitamin D trajectories from time of diagnosis through 10 years follow-up in early diagnosed RA patients. Me...
Article
Background A head-to-head trial (EXCEED) has indicated similar effectiveness of secukinumab (SEC) and the tumor necrosis factor inhibitor (TNFi) adalimumab (ADA) in psoriatic arthritis (PsA). In the clinical setting, treatment retention serves as a combined measure of overall effectiveness and tolerability. Objectives To explore baseline patient c...
Article
Background Disease activity in rheumatoid arthritis (RA) patients is measured through composite scores which are considered treatment targets and thus facilitate clinical decision making. Scores often combine a mix of objective and subjective measures, and, although the latter (e.g. pain, patient’s global, 28 tender joint count (TJC)) may be impact...