Désirée van der Heijde

Diakonhjemmet Hospital (Norway), Kristiania (historical), Oslo, Norway

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Publications (800)5059.17 Total impact

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    ABSTRACT: To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). 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 examination was performed by experienced sonographers using a validated grey-scale (GSUS) and power Doppler (PDUS) semiquantitative scoring system with scores 0-3 for both GSUS and PDUS in 36 joints and four tendons. We performed factor analysis in the early RA US data and selected candidate joint/tendon sets based on these results. The proportion of information in the total US scores retained in these candidate sets was assessed by R(2) from linear regression analysis. Finally, the candidate sets and previously proposed joint scores were tested in the established RA cohort, and we also evaluated the sensitivity to change with standardised response means. 227 patients with early RA and 212 patients with established RA were included. We identified two candidate sets of joints/tendons: candidate set A consisted of seven joints/two tendons (meatacarpophalangeal 1 (MCP1), MCP2, proximal interphalangeal 3, radiocarpal, elbow, metatarsophalangeal 1 (MTP1), MTP2, tibialis posterior tendon, extensor carpi ulnaris tendon) and set B of nine joints/two tendons (MCP5 and MTP5 added to set A). Unilateral reduced scores retained 78%-85% of the information in total score, while bilateral reduced scores retained 89%-93%, and both sets performed better than previously proposed reduced joint scores, and similar or slightly better regarding sensitivity to change. The reduced GSUS and PDUS scores retained most of the information from the total score and performed well in a validation cohort of established RA. NCT01205854, ACTRN12610000284066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 06/2015; DOI:10.1136/annrheumdis-2015-207572 · 9.27 Impact Factor
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    Tissue Antigens 06/2015; 85(6):497-8. DOI:10.1111/tan.12563 · 2.35 Impact Factor
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    ABSTRACT: Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis. The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints. JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage. Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs. Clinicaltrials.gov NCT00195663 . Registered 13 September 2005.
    Arthritis Research & Therapy 05/2015; 17(1). DOI:10.1186/s13075-015-0626-1 · 4.12 Impact Factor
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    ABSTRACT: The aim of this work was to develop a consensual recommendation under the auspices of the Assessment of SpondyloArthritis international Society (ASAS) for early referral of patients with a suspicion of axial spondyloarthritis by non-rheumatologists. The development of a referral recommendation consisted of four phases: (1) systematic literature review, (2) the first Delphi round aiming at identification of unmet needs and development of a candidate list of referral parameters, (3) the second Delphi round aiming at identification of the most useful combination of referral parameters and (4) final discussion and formal endorsement by ASAS membership. The following consensus on a referral recommendation was achieved as a result of the Delphi processes and final voting: "Patients with chronic back pain (duration ≥3 months) and back pain onset before 45 years of age should be referred to a rheumatologist if at least one of the following parameters is present: Inflammatory back pain; human leucocyte antigen-B27; Sacroiliitis on imaging if available (X-rays or magnetic resonance imaging); Peripheral manifestations (arthritis, enthesitis, dactylitis); Extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis); Positive family history for spondyloarthritis; Good response to non-steroidal anti-inflammatory drugs; Elevated acute phase reactant." A consensual ASAS-endorsed referral recommendation for patients suspected of having axial spondyloarthritis was developed as a flexible and universal strategy to be used in clinical practice by primary care physicians or non-rheumatology specialists. The practical value of this strategy applied in different settings should be determined in future studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 05/2015; DOI:10.1136/annrheumdis-2014-207151 · 9.27 Impact Factor
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    ABSTRACT: A systematic literature review (SLR; 2009-2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations. Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014. Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care. The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 05/2015; DOI:10.1136/annrheumdis-2015-207526 · 9.27 Impact Factor
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    ABSTRACT: To investigate 1) which spinal mobility measures (SMMs) are most frequently impaired in patients with AS, 2) whether a hierarchy of impairment could be established and 3) whether assessing fewer measures sufficiently captures impairment in spinal mobility. Patients from the Outcome in AS International Study (OASIS) were followed-up for 12 years. SMMs were considered impaired when falling below predefined cutoffs, derived from normal individuals. The proportion of patients in whom each SMM was impaired was calculated using baseline observation. In patients with ≥1 impaired SMM, we investigated how often impairment in spinal mobility would be missed if only a fixed number of SMMs was assessed. Analyses were repeated using all 12-year observations. A total of 216 patients were included (70% males). Lateral spinal flexion (LSF) was the most frequently impaired measure, followed by modified Schober (mSchober), tragus-to-wall, cervical rotation, intermalleolar distance and chest expansion, respectively. This hierarchy was strikingly consistent over time, and independent of gender, symptom duration and presence of syndesmophytes. In patients with ≥1 impaired SMM, LSF was impaired most frequently (86%), followed by mSchober (58%). If only LSF was measured, 14% of patients with impairment in any SMM would be missed; if additionally mSchober was measured, 9% would be missed. LSF followed by mSchober are the most frequently impaired mobility measures in AS, reflecting an earlier involvement of the lumbar spine, followed by involvement of the thoracic and cervical spine. In clinical practice LSF and mSchober suffice to screen impairment in spinal mobility. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    05/2015; DOI:10.1002/acr.22614
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    ABSTRACT: To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA). In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3). Ultrasound (US) was scored for synovial thickening and osteophytes, radiographs for osteophytes and JSN (Osteoarthritis Research Society International score), and anatomical phases (Verbruggen-Veys score). Pain was assessed during physical examination. Correlations of MRI with US and radiographic features were assessed with generalizability theory. With generalized estimating equations analyses, MRI features were associated with pain, adjusting for confounding. Forty-three percent, 27%, 77%, and 61% of joints had synovial thickening (moderate/severe), BML, osteophytes, and erosions on MRI, respectively. Intraobserver reliability, assessed in 6 patients, was good (ICC 0.77-1.00). Correlations between osteophytes, JSN, and erosions on radiographs and MRI were moderate, substantial, and fair (ICC 0.53, 0.68, and 0.32, respectively); MRI showed more lesions than radiography. Correlation between synovial thickening and osteophytes on MRI and US was moderate (ICC 0.43 and 0.49, respectively). MRI was more sensitive for synovial thickening, US for osteophytes. Pain was associated with moderate/severe synovial thickening (adjusted OR 2.4, 95% CI 1.06-5.5), collateral ligaments (4.2, 2.2-8.3), BML (3.5, 1.6-7.7), erosions (4.5, 1.7-12.2), and osteophytes (2.4, 1.1-5.2). MRI is a reliable and valid method to assess inflammatory and structural features in HOA. It gives additional information over radiographs and US.
    The Journal of Rheumatology 05/2015; DOI:10.3899/jrheum.140338 · 3.17 Impact Factor
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    ABSTRACT: To evaluate metric properties of the SpondyloArthritis Research Consortium of Canada (SPARCC) score of the sacroiliac (SI) joints. Patients with back pain (≥ 3 months, ≤ 2 years, onset < 45 years) were included in the SPACE cohort (SpondyloArthritis Caught Early). Patients with (possible) axial spondyloarthritis had followup visits after 3 and 12 months and were treated according to clinical practice. Magnetic resonance imaging (MRI) of the SI joints (MRI-SI) was scored in 2 independent campaigns (campaign 1: at baseline and 3 months; campaign 2: at baseline, 3 months, and 12 months) by 2 different blinded reader pairs, applying the Assessment of Spondyloarthritis International Society (ASAS) definition (MRI-SI+ vs MRI-SI-; discordant cases were adjudicated by a third reader) and SPARCC score (mean of 2 agreeing readers). Calculations were made for agreement between SPARCC score cutoff values and a consensus judgment of MRI-SI+ (ASAS definition) as external standard, change in SPARCC score, and smallest detectable changes (SDC) over 3 and 12 months. SPARCC score ≥ 2 showed best agreement with MRI-SI+ in both campaigns. Regarding observed changes in relation to SDC, SPARCC score changed in 70/151 patients; 26/70 patients changed > SDC (3.4), of whom 20 patients received stable treatment over 3 months in campaign 1. Over 3 months, 20/68 patients showed changes in SPARCC score; 11/20 > SDC (2.1), of whom 8 patients received stable treatment. Over 1 year, 23/74 patients changed their SPARCC score; 14/23 changed > SDC (2.4), of whom 7 received stable treatment in campaign 2. SPARCC score ≥ 2 can be used as surrogate for a consensus judgment of MRI-SI+ (ASAS definition) in clinical trials. The SDC ranged from 2.1-3.4 dependent on reader pair and were close to the proposed minimum important change of 2.5.
    The Journal of Rheumatology 05/2015; DOI:10.3899/jrheum.140806 · 3.17 Impact Factor
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    ABSTRACT: Objective. To test the feasibility of collecting, storing, retrieving and analysing necessary information to fulfil a preliminary set of quality indicators (QIs) that have been proposed by an international task force in a large multinational clinical practice database of patients with RA. Methods. Data from all 12 487 patients with 46 005 visits in the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology database from January 2008 until January 2012 were analysed to test the feasibility of collecting information on 10 QIs: time to diagnosis; frequency of visits; assessment of autoantibodies and radiographs, disease activity and function; disease remission, low disease activity, normal function; time to first DMARD and type of first DMARD. For each QI, two aspects were assessed: information availability and target achievement. Results. Information was available for <50% of patients regarding the following QIs: time to diagnosis, assessment of ACPAs or radiographs, time to first DMARD and type of first DMARD. Information was available for function assessment in 49% of visits and 67% of patients and for disease activity assessment in 85% of visits and 86% of patients. Information relevant to the QI frequency of visits was available for all patients. Relevant information to calculate the proportion of patients who achieved a defined target could be obtained for all QIs. Conclusion. Collecting storing, retrieving and analysing the core data necessary to meaningfully assess quality of care is feasible in a multinational, practice-based electronic database.
    Rheumatology (Oxford, England) 04/2015; DOI:10.1093/rheumatology/kev108 · 4.44 Impact Factor
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    ABSTRACT: A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 04/2015; 74(7). DOI:10.1136/annrheumdis-2014-206971 · 9.27 Impact Factor
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    ABSTRACT: To identify factors associated with elevated arterial stiffness in a 5-year follow-up of patients with ankylosing spondylitis (AS). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath AS disease activity index (BASDAI) and AS disease activity score (ASDAS) were recorded in 2003, and arterial stiffness (Augmentation Index (AIx) and pulse wave velocity (PWV)) in 2008/2009. Patients were grouped into quartiles according to baseline CRP, ESR and BASDAI and four ASDAS groups. Trend analyses were performed using ANCOVA (AIx/PWV as dependent variable) with separate models for CRP, ESR, BASDAI and ASDAS (age and gender adjusted). Independent predictors of future AIx and PWV levels were identified in multivariate linear regression models. In total, 85 patients participated. Increasing baseline values of CRP, ESR and ASDAS were associated with elevated AIx on follow-up (p(trend) 0.01, 0.05 and 0.04, respectively). Similar non-significant patterns were seen for PWV. In the multivariate analyses, baseline CRP and ASDAS were independently associated with future elevated AIx (p=0.03 and0.02, respectively). In the multivariate PWV model, results for CRP and ASDAS were non-significant. Baseline CRP and ASDAS were associated with future elevated arterial stiffness measured as AIx, supporting that disease activity is related to future risk of cardiovascular disease in patients with AS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 03/2015; DOI:10.1136/annrheumdis-2014-206773 · 9.27 Impact Factor
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    ABSTRACT: Evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in GO-REVEAL. The GO-REVEAL trial was a phase 3, randomized, double-blind trial with placebo-control through wk24 followed by an open-label extension of golimumab 50/100mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5/7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity [PtGA] score ≤20 (0-100), Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤0.5, and ≤1 tender enthesis point). Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at wk14 (23.5% vs. 1.0%; p<0.0001), wk24 (28.1% vs. 7.7%; p<0.0001), and wk52 (42.4% vs. 30.2%; p=0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomisation, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ-DI) and overall disease activity (PtGA) at wk256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ-DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio [95%CI]=0.514 [0.321,0.824]; p=0.006) and ≥4 (odds ratio [95%CI]=0.480 [0.290,0.795]; p=0.004) consecutive visits. Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis Care and Research 03/2015; DOI:10.1002/acr.22576 · 4.04 Impact Factor
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    ABSTRACT: To explore whether changes of MRI-defined synovitis and bone marrow lesions (BMLs) are related to changes in joint tenderness in a 5-year longitudinal study of the Oslo hand osteoarthritis (OA) cohort. We included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and contrast-enhanced synovitis in the distal and proximal interphalangeal joints were evaluated on 0-3 scales in n=69 and n=48 patients, respectively. Among joints without tenderness at baseline, we explored whether increasing/incident synovitis and BMLs were associated with incident joint tenderness using generalised estimating equations. Among joints with tenderness at baseline, we explored whether decreasing or resolution of synovitis and BMLs were associated with loss of joint tenderness. We adjusted for age, sex, body mass index, follow-up time and changes in radiographic OA. Among joints without tenderness at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220 (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant associations to incident joint tenderness were found for increasing/incident synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58) independent of structural progression. We found a trend that resolution of synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but these associations were non-significant. The Oslo hand OA cohort is the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were significantly associated with incident joint tenderness, whereas no significant associations were found for decreasing or loss of synovitis and BMLs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 03/2015; DOI:10.1136/annrheumdis-2014-206829 · 9.27 Impact Factor
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    ABSTRACT: Objectives: Few longitudinal studies have studied the association between body mass index (BMI) and hand osteoarthritis (OA). We aimed to explore the association between BMI and progressive hand OA in a longitudinal study of the Oslo hand OA cohort. Method: Participants with existing hand OA had hand radiographs and BMI data taken at baseline and 7-year follow-up (n = 103). The radiographs were read according to the Kellgren–Lawrence (KL) scale. First, we examined the association between baseline BMI and incident OA (KL grade ≥ 2) in joints without OA at baseline (adjusted for age and sex) using generalized estimating equation (GEE) analyses. Second, we examined whether changes in BMI from baseline to follow-up were associated with increasing KL sum score from baseline to follow-up using linear regression. We repeated the analyses using changes in number of joints with symptomatic OA and patient-reported pain and physical function as the outcome. Results: The mean (SD) age at baseline was 61.6 (5.6) years and 91 (94%) of the cohort were women. The mean (SD) BMI was 25.7 (4.0) kg/m2 at baseline and the mean (SD) BMI change was 1.1 (2.0) kg/m2. There was no relationship between baseline BMI and development of more joints with OA during follow-up. Similarly, there was no association between change in BMI and hand OA progression, increasing hand pain or disability. Conclusions: In the Oslo hand OA cohort, higher BMI was not related to hand OA progression.
    Scandinavian Journal of Rheumatology 03/2015; DOI:10.3109/03009742.2014.994560 · 2.61 Impact Factor
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    ABSTRACT: Objectives. To evaluate the efficacy and safety of sarilumab in combination with methotrexate (MTX) for treatment of rheumatoid arthritis (RA). Methods. Adults with moderate-to-severe RA and inadequate response to MTX were randomized (1:1:1) to sarilumab 150mg, 200 mg, or placebo every 2 weeks (q2w) with MTX for 52 weeks. Results. Baseline characteristics were similar among groups. For all three co-primary endpoints, sarilumab 150mg and 200mg groups demonstrated statistically significant improvements vs placebo: ACR20 response at Week 24 (58.0%, 66.4% vs 33.4%; p<0.0001), HAQ-DI at Week 16 (-0.53, -0.55, vs -0.29; p<0.0001) and mTSS at Week 52 (0.90, 0.25 vs 2.78; p<0.0001). The most common treatment-emergent adverse event was infection; serious infections incidence was 2.6%, 4.0%, and 2.3% (sarilumab 150mg, 200 mg, and placebo, respectively). Elevations in alanine aminotransferase >3-fold the upper limit of normal in 9.5%, 8.0%, and 2.1% of patients led to discontinuation of 24 patients. Elevated total cholesterol levels were observed in 36.8%, 43.0% and 18.3% of sarilumab 150mg, 200 mg and placebo patients, respectively. Neutrophil counts 500-<1000 Giga/L occurred in 5.1% and 7.8%, <500 Giga/L in 0.9% and 0.7% of sarilumab 150mg and 200mg patients, respectively, and none receiving placebo. Conclusions: In RA patients treated with sarilumab (150mg and 200mg q2w) in combination with MTX, both doses provided sustained clinical efficacy, significantly improving symptomatic, functional, and radiographic outcomes. Sarilumab was generally well tolerated. The adverse events observed in this study were consistent with IL-6 signaling blockade. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    03/2015; 67(6). DOI:10.1002/art.39093
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    ABSTRACT: Objective: Previous reports of RAPID-axSpA (NCT01087762) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks (wks) in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). We herein report efficacy and safety data from a 96-wk interim data cut of RAPID-axSpA. Methods: RAPID-axSpA is double-blind and placebo-controlled to Wk24, dose-blind to Wk48 and open-label to Wk204. Outcome variables assessed included ASAS20/40 and ASAS-partial remission responses (analyzed by non-responder imputation [NRI]), and ASDAS, ASDAS Inactive Disease, ASDAS Major Improvement, BASDAI, BASFI and BASMI-linear (analyzed by last observation carried forward [LOCF]). Safety data are shown for patients treated with ≥1 dose of CZP. Results: 325 patients were randomized, of whom 218 received CZP from Wk0. Of these, 93% completed Wk24, 88% Wk48 and 80% Wk96. Improvements in ASAS responses were maintained to Wk96 (ASAS20: 67.4%, 72.0%, 62.8% at Wks 24, 48, 96, respectively), as well as improvements in ASDAS, BASDAI (mean score: 3.3, 3.1, 3.0 at Wks 24, 48, 96, respectively), BASFI and BASMI-linear. Comparable improvements were observed with both dosing regimens (200mg Q2W/400mg Q4W) and in AS and nr-axSpA patients. In the Safety Set, adverse events occurred in 279 patients (88.6%) and serious adverse events in 41 (13.0%). No deaths or malignancies were reported. Conclusion: Clinical improvements to Wk24 in both CZP dosing regimens were sustained to Wk96. Similar sustained improvements were observed in AS and nr-axSpA subpopulations. The safety profile was in-line with previous reports from RAPID-axSpA, with no new safety signals observed with longer exposure duration. This article is protected by copyright. All rights reserved. Copyright © 2014 American College of Rheumatology.
    03/2015; 67(3). DOI:10.1002/art.38973
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    ABSTRACT: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. 3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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    ABSTRACT: To compare the risk of cardiovascular disease (CVD) in ankylosing spondylitis (AS) and population controls, and to examine the associations between disease activity and CVD risk. A cross-sectional study was done of patients with AS grouped according to Ankylosing Spondylitis Disease Activity Score (ASDAS) into ASDAS-high and ASDAS-low. Markers of vascular pathology, impaired endothelial function [asymmetric dimethylarginine (ADMA)], and arterial stiffness [augmentation index (AIx) and pulse wave velocity (PWV)], and traditional CVD risk factors [blood pressure, lipids, body mass index (BMI), CVD risk scores] were compared between AS and controls as well as across ASDAS-high versus ASDAS-low versus controls using ANCOVA analyses. Altogether, 151 patients with AS and 134 controls participated. Patients had elevated ADMA (μmol/l) and AIx (%) compared to controls: mean difference (95% CI): 0.05 (0.03, 0.07), p < 0.001 and 2.6 (0.8, 4.3), p = 0.01, respectively. AIx increased with higher ASDAS level, p(trend) < 0.04. There were no significant group differences of PWV. BMI was higher in ASDAS-high compared to ASDAS-low (p = 0.02). Total cholesterol was lower in AS compared to controls, and lower with higher ASDAS, p(trend) = 0.02. CVD risk scores were similar across groups except for Reynolds Risk Score, where the ASDAS-high group had a significantly higher score, compared to both ASDAS-low and controls. Elevated ADMA and AIx in AS support a higher CVD risk in AS. Elevated AIx and BMI in AS with high ASDAS indicate an association between disease activity and CVD risk. Lower total cholesterol in AS may contribute to underestimation of CVD risk.
    The Journal of Rheumatology 02/2015; 42(4). DOI:10.3899/jrheum.141018 · 3.17 Impact Factor
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    ABSTRACT: To evaluate whether intravenous gadolinium (Gd) contrast administration can be eliminated when evaluating synovitis and tenosynovitis in early arthritis patients, thereby decreasing imaging time, cost, and invasiveness. Wrist MRIs of 93 early arthritis patients were evaluated by two readers for synovitis of the radioulnar, radiocarpal, and intercarpal joints, according to the Rheumatoid Arthritis MRI Scoring method (RAMRIS), and for tenosynovitis in ten compartments. Scores of MRI images without Gd contrast enhancement were compared to scores obtained when evaluating all, including contrast-enhanced, MRI images as reference. Subsequently, a literature review and pooled analysis of data from the present and two previous studies were performed. At the individual joint/tendon level, sensitivity to detect synovitis without Gd contrast was 91 % and 72 % for the two readers, respectively, with a specificity of 51 % and 81 %. For tenosynovitis, the sensitivity was 67 % and 54 %, respectively, with a specificity of 87 % and 91 %. Pooled data analysis revealed an overall sensitivity of 81 % and specificity of 50 % for evaluation of synovitis. Variations in tenosynovitis scoring systems hindered pooled analyses. Eliminating Gd contrast administration resulted in low specificity for synovitis and low sensitivity for tenosynovitis, indicating that Gd contrast administration remains essential for an optimal assessment. • Eliminating gadolinium contrast administration results in low specificity for synovitis • For tenosynovitis, sensitivity is low without gadolinium contrast administration • Gadolinium contrast administration remains essential for evaluating synovitis and tenosynovitis in early arthritis.
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    ABSTRACT: To test medication adherence using the Compliance-Questionnaire-Rheumatology (CQR). Invitation letter and CQR were sent to 240 patients with rheumatoid arthritis. Followup CQR was sent 3 months later. Adherence was evaluated using CQR 80% cutoff scores. Seventy-eight patients who were being treated with disease-modifying antirheumatic drugs provided full information on the CQR at both points in time. Eleven patients (14.1%) were classified as adherent based on taking compliance (TC), with only 3 patients (3.8%) adherent in regard to correct dosing (CD) [followup: 13 (16.7%) and 3 (3.8%) for TC and CD, respectively]. Nonadherence was not related to disease activity or side effects. We demonstrated low adherence, suggesting differences between doctors' records and patients' practice of antirheumatic drug therapy.
    The Journal of Rheumatology 01/2015; 42(3). DOI:10.3899/jrheum.140982 · 3.17 Impact Factor

Publication Stats

31k Citations
5,059.17 Total Impact Points

Institutions

  • 2007–2015
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo, Norway
    • University of Alberta
      • Department of Medicine
      Edmonton, Alberta, Canada
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
    • Toronto Western Hospital
      Toronto, Ontario, Canada
    • Ludwig-Maximilian-University of Munich
      • Department of Physical Medicine and Rehabilitation
      München, Bavaria, Germany
  • 2005–2015
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
    • University of the Pacific (California - USA)
      Stockton, California, United States
    • Medisch Centrum Leeuwarden
      Leewarden, Friesland, Netherlands
    • German Rheumatism Research Centre
      Berlín, Berlin, Germany
  • 2014
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
    • Oregon Health and Science University
      Portland, Oregon, United States
  • 2007–2014
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2013
    • Novartis Institutes for BioMedical Research
      Cambridge, Massachusetts, United States
  • 2010–2013
    • Medical University of Vienna
      Wien, Vienna, Austria
    • Medisch Centrum Haaglanden
      's-Gravenhage, South Holland, Netherlands
  • 2005–2013
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2012
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
    • Laval University
      Quebec City, Quebec, Canada
  • 1997–2012
    • University of Leeds
      • School of Medicine
      Leeds, England, United Kingdom
  • 2011
    • Arthritis Research UK
      Chesterfield, England, United Kingdom
  • 2005–2011
    • University of Toronto
      Toronto, Ontario, Canada
  • 2002–2011
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1997–2011
    • Maastricht University
      • Department of Internal Medicine
      Maestricht, Limburg, Netherlands
  • 1998–2009
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2008
    • Menzies Research Institute
      Hobart Town, Tasmania, Australia
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 2004–2007
    • University of Washington Seattle
      Seattle, Washington, United States
    • Carol Davila University of Medicine and Pharmacy
      • Department of Internal Medicine and Rheumatology
      Bucharest, Bucuresti, Romania
  • 2000–2006
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2003–2005
    • Boston University
      Boston, Massachusetts, United States
    • St. Josefs Hospital
      Клоппенбург, Lower Saxony, Germany
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
  • 2001–2004
    • Stanford University
      • Division of Immunology
      Palo Alto, California, United States
  • 1999
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1989–1992
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands