Espen Andre Haavardsholm

Diakonhjemmet Hospital (Norway) · Dept. of Rheumatology

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in...

With recent improvements in the treatment of rheumatoid arthritis (RA), remission has become an achievable goal for a large proportion of RA patients, and remission is now a defined target in current RA guidelines. However, studies have shown that progression of radiographic joint damage may occur in clinical remission, regardless of the choice of...

Objectives To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). Methods Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naïve early RA or established RA starting/switching biologics. An extensive US ex...

The association between joint damage and disability in rheumatoid arthritis (RA), especially in the later stages of disease, is a main reason why radiographic joint damage is a common and valid outcome measure in RA clinical trials. Most studies have assessed the effect of global joint damage, which has limited our knowledge regarding the individua...

To investigate whether baseline disease activity levels and responses in patients with rheumatoid arthritis (RA) changed during the period 2000-2010. Data were provided by the Norwegian disease-modifying antirheumatic drug (NOR-DMARD) study. Patients with inflammatory joint diseases starting new treatment with disease-modifying antirheumatic drugs...

Objectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA). Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including par...

Background As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibito...

Objective The objective of this study was to determine if baseline adiponectin, leptin, and resistin levels are associated with response to antirheumatic treatment in early rheumatoid arthritis (RA). Methods This study included 341 participants of the Nordic Rheumatic Diseases Strategy Trials and Registries trial with untreated early RA, randomize...

Objective The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics bef...

Objectives Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. Methods Patients in the NOR-Gout obs...

Objectives To explore the agreement between patient-reported flare status and clinically significant flare status in patients with rheumatoid arthritis (RA) in sustained remission. Method Patients with RA in remission for ≥12 months on stable treatment were included in the ARCTIC REWIND tapering trials and pooled 12-month data used in current anal...

Objectives To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). Methods Patients with treatment-naïve early rheumatoid arthritis...

Clinical trials are essential for evaluating the efficacy and safety of new treatments and health interventions. However, while pharmacological trials are well-established, non-pharmacological trials face unique challenges related to their complexity and difficulties such as recruitment, retention, intervention standardisation, selection of outcome...

Background Predicting drug response would be useful but has proven difficult. Two Norwegian cohorts of early or established rheumatoid arthritis (RA) patients included in a Nordic multi-centre study exploring personalized medicine in RA, the NORA/ScandRA consortia, were used to evaluate the predictive value of inflammatory markers as well as clinic...

Background Ultrasound (US) is sensitive for detecting monosodium urate (MSU) crystal depositions in gout, described as double contour (DC), tophi and aggregates. After persistent urate lowering treatment (ULT) we had at 1 year seen a significant decrease of the US depositions of MSU, and 85.3% of patients achieved the serum uric acid (sUA) target o...

Background The SARS-CoV-2 virus mutates continuously, posing challenges for patients with immune-mediated inflammatory diseases (IMIDs) on tumour necrosis factor inhibitors (TNFi). These patients often have diminished vaccine responses and are at a higher risk for severe infections. The efficacy of the recommended mono- and bivalent vaccine booster...

Background Tapering of tumor necrosis factor inhibitor (TNFi) treatment in patients who have reached sustained remission is debated in current guidelines, and further data are needed regarding the long-term consequences of such strategies. Objectives To assess the 3-year effects of tapering and withdrawal of TNFi versus continuing stable TNFi on d...

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapies have attenuated humoral vaccine responses and are prone to more severe infections. Assessing the persistence of cellular and humoral immunity following repeated SARS-CoV-2 vaccine doses and infection is important to evaluate the need for booster va...

Background Patients with inflammatory joint diseases on immunosuppressive therapies are vulnerable to severe COVID-19 and are recommended to receive targeted vaccine boosters. Since these patients were excluded from phase 3 vaccine trials, it is important to evaluate safety of the updated XBB.1.5 vaccine as a 3rd booster dose in this patient group....

Background The randomized controlled NORD-STAR trial demonstrated remission rates of 40-60% in patients with early rheumatoid arthritis (RA) at 24 and 48 weeks according to the Clinical Disease Activity Index (CDAI) when treated early with methotrexate in combination with prednisolone (active conventional therapy (ACT)), certolizumab pegol (CZP), a...

Background Patients on immunosuppressive therapies have diminished humoral vaccine responses to SARS-CoV-2 vaccines. Cellular immunity is crucial for long-term protection against severe COVID-19. Interferon gamma release assay (IGRA) SARS-CoV-2 tests are now commercially available for evaluation of cellular responses in clinical practice. Knowledge...

Background Ultrasound (US) is sensitive for detecting monosodium urate (MSU) crystal depositions in gout, described as double contour (DC), tophi and aggregates. Depositions decreased during the first year of serum urate lowering treatment (ULT) in the NOR-Gout study [1]. Objectives As part of the NOR-Gout study to explore the US changes in deposi...

Background Previous studies have suggested that rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) positivity selectively associates with better responses to abatacept treatment in early rheumatoid arthritis (RA). Objectives To investigate whether RF, ACPA, and shared epitope (SE) alone or in combination predict treatment r...

Background Novel follow-up strategies such as Remote Monitoring and Patient-initiated Care may allow for more targeted and efficient use of health-care resources compared to conventional prescheduled face-to-face outpatient visits. However, knowledge regarding the effectiveness of these strategies is scarce. This is the first randomized clinical tr...

Background Collagen type II (CII) is the major protein in hyaline cartilage. We have previously detected anti-CII autoantibodies in a small subgroup (7-9%) of rheumatoid arthritis (RA) patients at the time of diagnosis (1,2). After forming immune complexes with surface-bound CII in vitro, anti-CII induce cytokines and chemokines via FcgRIIa- and TL...

Background Glucocorticoids (GCs) are commonly used as part of the initial treatment in patients diagnosed with rheumatoid arthritis (RA) to rapidly suppress inflammation, a strategy often referred to as bridging therapy. However, due to concerns about adverse events and patients not being able to discontinue GCs after the intended bridging period,...

Background A majority of patients with rheumatoid arthritis (RA) display autoantibodies targeting IgG Fc (rheumatoid factor, RF), and/or post-translationally modified proteins including anti-citrullinated (ACPA), anti-carbamylated (anti-Carb), and anti-acetylated (anti-Acet) protein antibodies. ACPA are highly specific for RA and are important clin...

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease with variable clinical presentation, response to therapy, and long-term outcomes. Currently, there is a lack of predictive biomarkers to guide an individualized treatment strategy. Combinations of conventional and novel serological biomarkers might stratify patients for a more p...

Background The variability in treatment response in people with rheumatoid arthritis (RA) warrants the prediction of patients at high risk of treatment failure. Identification of biomarkers linked to clinical remission in RA is currently a challenge. Metabolomics may help to identify such biomarkers as it allows for a comprehensive exploration of d...

Objective This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA). Methods This report included 793 participants with untreated early RA from the randomised, lon...

Objectives To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. Methods IMIDs on...

Background SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods We included 76 RA patients treated with rituximab...

Background Understanding T cell responses to SARS-CoV-2 immunisation in patients on immunosuppressive treatment is important for future vaccine recommendations. Our aim was to investigate the magnitude and quality of T cell responses following repeated SARS-CoV-2 vaccine doses and COVID-19 (breakthrough infections). Methods In this prospective, ob...

Objective We investigated methotrexate safety and the influence of dose on efficacy outcomes in combination with three different biologic treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). Methods This post hoc analysis included 812 treatment‐naïve patients with early RA who were randomized (1:1:1:1) in the...

Objectives To explore the performance of the EULAR-initiated patient-reported Rheumatoid Arthritis Impact of Disease (RAID) questionnaire in relation to flares in disease activity, including comparison with other disease activity outcomes. Methods Patients with rheumatoid arthritis in sustained remission were randomised to continued stable treatme...

Background Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technol...

Objective Gout is associated with lifestyle, body mass index (BMI) and comorbidities, including dyslipidaemia. We studied how in actively treated patients, anthropometric measures and lipid levels changed over 2 years and whether they predicted gout outcomes. Methods Patients with a recent gout flare and elevated serum urate (sUA) received gout ed...

Objectives To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of adalimumab. Also, to assess the occurrence and risk factors of anti-drug antibody (ADAb) formation. Methods Non-trough adalimumab and ADAb levels were measured by automa...

BACKGROUND Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technol...

Objectives Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable t...

Background The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. Methods Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA...

Objective: Adherence to urate-lowering therapy (ULT) in gout is challenging. This longitudinal study aimed to determine 2 year changes in beliefs about medicines during intervention with ULT. Method: Patients with a recent gout flare and increased serum urate received a nurse-led ULT intervention with tight control visits and a treatment target....

Calprotectin (S100A8/S100A9, MRP8/MRP14) is a major leukocyte protein found to be more sensitive than C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) as a marker of inflammation in patients with rheumatoid arthritis (RA). The present objective was to explore the robustness of calprotectin assessments by comparing two different lab...

Background Inflammatory laboratory markers predicting response to medication would be useful in the clinics. Two Norwegian cohorts of early or established RA patients included in the NORA study (a Nordic multi-centre study exploring personalized medicine in RA) were used to explore the predictive value of calprotectin, C-reactive protein (CRP) and...

Background Several therapeutic options are currently available to treat rheumatoid arthritis (RA); however, the response to treatment is highly variable, and not all patients achieve clinical remission [1]. Obesity is suggested to lower the chances of remission [2], even though a recent observational study has shown that obesity is not associated w...

Background The formation of neutrophil extracellular traps (NETs) with extrusion of nuclear, granular and cytosolic components from a dying neutrophil, has been described extensively in patients with rheumatoid arthritis (RA), and linked to generation of autoantigens (e.g. citrullinated proteins), inflammation and organ damage. Thus far there have...

Background Patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapies are known to be at greater risk of severe COVID-19 disease, hospitalisation and death. Protective levels of anti-Spike antibodies following vaccination are yet to be determined. Objectives To examine whether post-vaccination anti-Spike antibody le...

Background Safety and efficacy of updated bivalent vaccines, containing both the original vaccine variant of SARS-CoV-2 Spike and either Omicron variants BA.1 or BA.4/5, are of particular interest in arthritis patients on immunosuppressive therapies. With the continuous emergence of new viral variants, it is important to evaluate whether updated va...

Background Serum drug levels and anti-drug antibodies (ADAb) impact the therapeutic effectiveness of most TNF-inhibitors. Possible differences in immunogenicity profile and pharmacokinetics across biosimilar and originator TNFi are still to be elucidated. Objectives To compare serum drug levels, ADAb and treatment effect in patients treated with o...

Background Lack of response to TNF-inhibitors (TNFi) can be caused by subtherapeutic drug levels and anti-drug antibodies (ADAb). Therapeutic-drug-monitoring (TDM) can help clinicians tailor treatment and may improve effectiveness, safety and cost-effectiveness of TNFi. For TDM to be validated as a clinical tool, therapeutic ranges must be identifi...

Background Tapering of disease modifying antirheumatic drugs (DMARDs) to achieve drug-free remission is a goal for the growing group of rheumatoid arthritis (RA) patients in remission. However, the long-term effects of tapering or withdrawal of DMARDs remain unclear. Objectives To compare the 3-year clinical and radiographic outcomes of three conv...

Background Neutralising anti-drug antibodies (ADAb) are a problem in treatment with TNF-inhibitors (TNFi). Prospective data are needed to better understand how ADAb formation impacts safety and treatment outcomes of TNFi. Proactive therapeutic drug monitoring (TDM) allows for timely detection of ADAb and this strategy may have a role in reducing th...

Background T cells are critical for control of viral infection with SARS-CoV-2, but knowledge is lacking on cellular immune responses following repeated vaccination and breakthrough infection in immunosuppressed patients. Objectives To examine longitudinal T cell responses across diagnoses, following vaccine series and COVID-19 in patients on tumo...

Background Gout causes pain and reduced health related quality of life. There are no longitudinal studies on work productivity in patients who are being treated-to target for their serum urate in clinical practice. Objectives We examined whether work productivity in gout patients changed over 2 years after intensive treatment with ULT, and if dise...

Background Gout is caused by depositions of monosodium uric acid crystals in joints and tissues which triggers highly painful flares. Serum urate lowering treatment (ULT) reduces the number of flares. Objectives To explore the change of crystal depositions assessed by ultrasound and dual energy computer tomography (DECT) for two years, and the ass...

Background The Rheumatoid Arthritis Impact of Disease (RAID) is a patient-reported outcome measure (PROM) originating from a EULAR initiative. It supports patient-centered care and shared decision-making between patient and rheumatologist regarding treatment and adjustment of medication. RAID could be a useful tool in remote monitoring, and its ass...

This open-label randomized clinical trial assessed the 12-month risk of disease activity flares after discontinuation of conventional synthetic DMARDs (csDMARDs) compared with continuing half-dose csDMARDs in adult Norwegian patients with rheumatoid arthritis and excellent disease control.

Background: Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti-drug antibody (ADAb) formation to infliximab. Methods: Immune-mediated inflammatory disease patients on infliximab therap...

Methotrexate is one of the cornerstones of rheumatoid arthritis (RA) therapy. Genetic factors or single nucleotide polymorphisms (SNPs) are responsible for 15%–30% of the variation in drug response. Identification of clinically effective SNP biomarkers for predicting methotrexate (MTX) sensitivity has been a challenge. The aim of this study was to...

Objectives To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. Methods An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocortic...

Objectives Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this...

Background Data on response and safety of repeated vaccinations and hybrid immunity in patients with immune-mediated inflammatory diseases on immunosuppressive therapy is needed to further develop vaccination strategies in this vulnerable population. This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-Co...

Background: The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy control...

Background: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore...

Background Rheumatoid arthritis is a chronic inflammatory disease with a well-recognised female preponderance. In this post-hoc analysis of the NORD-STAR trial, we aimed to examine sex differences in remission rates with three different biological treatments combined with methotrexate versus active conventional treatment over 24 weeks, in patients...

Background Gout is of unknown reason associated with cardiovascular disease. Ultrasound is sensitive for detecting crystal deposition and plasma calprotectin is a sensitive inflammatory marker. This study explores the associations between crystal deposition, inflammation and carotid artery pathology. Method A cross-sectional analysis of baseline a...

Objective Immunogenicity and safety following receipt of the standard SARS–CoV‐2 vaccination regimen in patients with immune‐mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard...

Background: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions to optimize it and contribute to an international consensus. Furthermore,...

Background Patients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients. Objectives To assess the effects of different initial treatments on hemostatic parameters in patients...

Background Active collaboration between patients and researchers in development and implementation of scientific projects is important to ensure a good match between patient’s preferences and the scientific focus in research, contribute to more patient-oriented health research agendas, enhance patient friendly design of research projects, and creat...

Background Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity against SARS-CoV-2 differs between this patient population and the general public is currently unknown....

Background The optimal first-line treatment of patients with early rheumatoid arthritis (eRA) is not established. Objectives To compare clinical and radiographic outcomes of active conventional therapy (ACT) with each of three biological therapies with different modes of action. Methods In this investigator-initiated, randomized, open-label, blin...

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy have an inadequate serologic response following two-dose SARS-CoV-2 vaccination, and a standard vaccination strategy of three doses for this patient group is currently under implementation in several countries. However, the serological response and s...

Background Plasma calprotectin is a sensitive inflammatory marker in patients with rheumatoid arthritis (RA) and reflects activation of granulocytes and macrophages. Plasma calprotectin has not previously been studied in a head-to-head trial of multiple biological mechanisms of action versus active conventional therapy (ACT) with methotrexate and p...