Désirée van der Heijde

University of Oslo, Kristiania (historical), Oslo, Norway

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Publications (543)3218.55 Total impact

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    ABSTRACT: Introduction This 28-week, phase IIIb study assessed safety and maintenance of response to certolizumab pegol (CZP) in a diverse population of rheumatoid arthritis (RA) patients, stratified by prior anti-TNF exposure, concomitant methotrexate (MTX) use and disease duration. The ability to predict achievement of low disease activity (LDA) at week 28 from improvements in Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) and Clinical Disease Activity Index (CDAI) up to week 12 was assessed. Methods The 28-week study population included all patients who completed the double-blind (DB) phase and entered the open-label (OL) phase, receiving 200 mg CZP every 2 weeks (Q2W) ≥16 weeks. In the 12-week DB period, patients with active RA and an inadequate response to ≥1 disease-modifying antirheumatic drug (DMARD) were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4 then 200 mg Q2W) or placebo (Q2W), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years). Results A total of 955 patients entered the OL phase. At week 28, similar clinical improvements were seen in those receiving CZP throughout (CZP → CZP; n = 771) and those receiving placebo during the DB phase and switching to CZP in the OL phase (placebo → CZP; n = 184) (ACR20 response rate = 59.7 % vs. 53.3 %; ACR50/ACR70 response rates were also similar). Effect of CZP treatment was similar regardless of prior anti-TNF use, disease duration and concomitant DMARDs, based on ACR20 response rates. The percentage of patients achieving DAS28(ESR) LDA at week 28 was calculated for DAS28(ESR), SJC or CDAI responders at earlier time points. Reductions from baseline (Δ) of DAS28(ESR) <1.2, ΔSJC <25 % or ΔCDAI <10 by week 12 were associated with <9 % chance of achieving LDA at week 28 regardless of prior anti-TNF exposure. Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified. Conclusions A diverse population of RA patients with varying disease duration showed rapid and sustained clinical improvements on CZP treatment, regardless of prior anti-TNF or concomitant DMARD use. Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28. No new safety signals were observed. Trial registration ClinicalTrials.gov, NCT00717236, 15 July 2008 Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0841-9) contains supplementary material, which is available to authorized users.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0841-9 · 3.75 Impact Factor
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    ABSTRACT: Objectives: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results: Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions: Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number: JapicCTI-101263.
    Annals of the rheumatic diseases 11/2015; DOI:10.1136/annrheumdis-2015-208052 · 10.38 Impact Factor
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    ABSTRACT: Objective: To compare the total amount of physical activity (TPA) and time spent in various activity intensities of patients with ankylosing spondylitis (AS) and population controls, and to explore factors related to physical activity (PA). Methods: Subjects were asked to wear a triaxial accelerometer for 7 days and to complete a series of questionnaires. Multivariable regressions were used to assess generic determinants of TPA in patients and controls, and in patients to explore demographic and disease-specific determinants of various PA intensities. Results: One hundred and thirty-five patients [51 ± 13 yrs, 60% men, body mass index (BMI) 26.0 ± 4.3 kg/m(2)] and 99 controls (45 ± 12 yrs, 67% men, BMI 25.1 ± 4.3 kg/m(2)) were included. Patients did not differ from controls regarding TPA (589 vs 608 vector count/min, p = 0.98), minutes/day spent in sedentary (524 vs 541, p = 0.17), and light PA (290 vs 290 p = 0.95), but spent fewer minutes/day in moderate to vigorous PA (MVPA; 23 vs 30 min/day, p = 0.006). Perceived functional ability (physical component summary of the Medical Outcomes Study Short Form-36) and BMI were associated with TPA independent of having AS (p interaction = 0.21 and 0.94, respectively). Additional analyses in patients showed that time spent in MVPA was negatively influenced by BMI, physical function (Bath AS Functional Index), and disease duration. In patients ≥ 52 years old, a higher Bath AS Disease Activity Index was associated with less time spent in sedentary and more time spent in light activities. Conclusion: Compared with controls, patients with AS had similar TPA, but may avoid engagement in higher intensities of PA. Lower levels of functional ability and higher BMI were associated with lower TPA in both patients and controls.
    The Journal of Rheumatology 11/2015; DOI:10.3899/jrheum.150015 · 3.19 Impact Factor
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    ABSTRACT: Background: Increased risk of some comorbidities has been reported in spondyloarthritis (SpA). Recommendations for detection/management of some of these comorbidities have been proposed, and it is known that a gap exists between these and their implementation in practice. Objective: To evaluate (1) the prevalence of comorbidities and risk factors in different countries worldwide, (2) the gap between available recommendations and daily practice for management of these comorbidities and (3) the prevalence of previously unknown risk factors detected as a result of the present initiative. Methods: Cross-sectional international study with 22 participating countries (from four continents), including 3984 patients with SpA according to the rheumatologist. Statistical analysis: The prevalence of comorbidities (cardiovascular, infection, cancer, osteoporosis and gastrointestinal) and risk factors; percentage of patients optimally monitored for comorbidities according to available recommendations and percentage of patients for whom a risk factor was detected due to this study. Results: The most frequent comorbidities were osteoporosis (13%) and gastroduodenal ulcer (11%). The most frequent risk factors were hypertension (34%), smoking (29%) and hypercholesterolaemia (27%). Substantial intercountry variability was observed for screening of comorbidities (eg, for LDL cholesterol measurement: from 8% (Taiwan) to 98% (Germany)). Systematic evaluation (eg, blood pressure (BP), cholesterol) during this study unveiled previously unknown risk factors (eg, elevated BP (14%)), emphasising the suboptimal monitoring of comorbidities. Conclusions: A high prevalence of comorbidities in SpA has been shown. Rigorous application of systematic evaluation of comorbidities may permit earlier detection, which may ultimately result in an improved outcome of patients with SpA.
    Annals of the rheumatic diseases 10/2015; DOI:10.1136/annrheumdis-2015-208174 · 10.38 Impact Factor
  • Denis Poddubnyy · Astrid van Tubergen · Robert Landewé · Joachim Sieper · Désirée van der Heijde ·

    Annals of the rheumatic diseases 10/2015; DOI:10.1136/annrheumdis-2015-208553 · 10.38 Impact Factor
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    ABSTRACT: Objective: Description of use and metric properties of instruments measuring pain, physical function, or patient's global assessment (PtGA) in hand osteoarthritis (OA). Methods: Medical literature databases up to January 2014 were systematically reviewed for studies reporting on instruments measuring pain, physical function, or PtGA in hand OA. The frequency of the use of these instruments were described, as well as their metric properties, including discrimination (reliability, sensitivity to change), feasibility, and validity. Results: In 66 included studies, various questionnaires and performance- or assessor-based instruments were applied for evaluation of pain, physical function, or PtGA. No major differences regarding metric properties were observed between the instruments, although the amount of supporting evidence varied. The most frequently evaluated questionnaires were the Australian/Canadian Hand OA Index (AUSCAN) pain subscale and visual analog scale (VAS) pain for pain assessment, and the AUSCAN function subscale and Functional Index for Hand OA (FIHOA) for physical function assessment. Excellent reliability was shown for the AUSCAN and FIHOA, and good sensitivity to change for all mentioned instruments; additionally, the FIHOA had good feasibility. Good construct validity was suggested for all mentioned questionnaires. The most commonly applied performance- or assessor-based instruments were the grip and pinch strength for the assessment of physical function, and the assessment of pain by palpation. For these measures, good sensitivity to change and construct validity were established. Conclusion: The AUSCAN, FIHOA, VAS pain, grip and pinch strength, and pain on palpation were most frequently used and provided most supporting evidence for good metric properties. More research has to be performed to compare the different instruments with each other.
    The Journal of Rheumatology 10/2015; 42(11). DOI:10.3899/jrheum.141228 · 3.19 Impact Factor
  • Pedro M Machado · Xenofon Baraliakos · Désirée van der Heijde · Jürgen Braun · Robert Landewé ·
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    ABSTRACT: Objectives: To study the sequential relationship between MRI vertebral corner inflammation (VCI), vertebral corner fat deposition (VCFD) and the development/growth of radiographic syndesmophytes at the same vertebral corner (VC). Methods: Baseline, 24 and 102 weeks spinal MRIs were assessed for the presence/absence of VCI and VCFD. Anterior VCs of lateral radiographs of the cervical and lumbar spine (baseline and 102 weeks) were assessed for the development of new bone (syndesmophyte formation or syndesmophyte formation/growth combined). Data from 161 to 177 patients were analysed at the VC level using two-way and multilevel analyses adjusting for within-patient correlation and MRI reader (generalised estimating equations for binomial outcomes). Results: The presence of VCI (adjusted (adj) OR 1.75 to 1.98) as well as the presence of VCFD (adjOR 1.60 to 2.32) at any time point (TP) were significantly associated with the development of new bone. The combination of VCI and VCFD at the same VC increased the strength of the association, both for the sequential or simultaneous presence of VCI and VCFD across the three TPs (adjOR 2.12 to 2.73), as well as for the development of new VCFD preceded by VCI at a previous TP (adjOR 2.12 to 3.01). The complete absence of both VCI and VCFD across the three TPs 'protected' against new bone formation (adjOR 0.45 to 0.62). However, 40-66% of new bone still developed in VCs without MRI inflammation or fat degeneration at any of the three TPs. Conclusions: Both VCI and VCFD contribute to new bone formation in ankylosing spondylitis (AS), especially if VCI precedes VCFD. However, VCI, VCFD and this particular sequence of events only partially explain the development of new bone in AS.
    Annals of the rheumatic diseases 10/2015; DOI:10.1136/annrheumdis-2015-208011 · 10.38 Impact Factor

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    ABSTRACT: Background In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients. Methods In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains. Results ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group. Conclusions Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326 .).
    New England Journal of Medicine 09/2015; 373(14):1329-1339. DOI:10.1056/NEJMoa1412679 · 55.87 Impact Factor
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    ABSTRACT: Objectives: To investigate the longitudinal relationship between inflammatory lesions in sacroiliac joints on MRI (MRI-SI) and clinical disease activity measures (DA) in patients with axial spondyloarthritis (axSpA). Methods: Two-year follow-up data from 167 patients (50% males, mean (SD) age 33 (9) years) fulfilling the Assessment of SpondyloArthritis international Society axSpA criteria in the DEvenir des Spondylarthopathies Indifférenciées Récentes cohort with MRI-SI at baseline, 1 year and 2 years were analysed. The relationship between MRI-SI (as dependent variable) and DA (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient's global DA, night pain, C reactive protein and erythrocyte sedimentation rate, as independent variables) was investigated using two types of generalised estimating equations (GEE) models: model of absolute scores and model of change scores. Results: In the model of absolute scores, the relationship between DA and MRI-SI was different for males and females: in males, but not in females, a statistically significant relationship with MRI-SI was found for all DA except BASDAI. In the model of changes, only ASDAS (beta (95% CI): 2.79 (0.85 to 4.73) and pain at night (0.97 (0.04 to 1.90)) were significantly associated in males while again in females no significant relationship was found. ASDAS fitted the data best. Conclusions: In male patients, but not in female patients, with axSpA, clinical DA, especially if measured by ASDAS, is longitudinally associated with MRI-SI inflammatory lesions.
    Annals of the rheumatic diseases 09/2015; DOI:10.1136/annrheumdis-2015-207786 · 10.38 Impact Factor
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    ABSTRACT: Our objective was to identify distinct trajectories of disease activity state (DAS) and assess variation in radiographic progression, function and quality of life over the first two years of early rheumatoid arthritis (ERA). The CATCH (Canadian early ArThritis CoHort) is a prospective study recruiting ERA patients from academic and community rheumatology clinics in Canada. Sequential DAS28 scores were used to identify five mutually exclusive groups in the cohort (n = 1,586) using growth-based trajectory modeling. Distinguishing baseline sociodemographic and disease variables, treatment required, and differences in radio-graphic progression and quality of life measures over two years were assessed. The trajec-tory groups are characterized as: Group 1 (20%) initial high DAS improving rapidly to remission (REM); Group 2 (21%) initial moderate DAS improving rapidly to REM; Group 3 (30%) initial moderate DAS improving gradually to low DAS; Group 4 (19%) initial high DAS improving continuously to low DAS; and Group 5 (10%) initial high DAS improving gradually only to moderate DAS. Groups differed significantly in age, sex, race, education, employment , income and presence of comorbidities. Group 5 had persistent steroid requirements and the highest biologic therapy use. Group 2 had lower odds (OR 0.22, 95%CI 0.09 to 0.58) and Group 4 higher odds (OR 1.94, 95%CI 0.90 to 4.20) of radiographic progression compared to Group 1. Group 1 had the best improvement in physical function (Health Assessment Questionnaire 1.08 (SD 0.68) units), Physical Component Score (16.4
    PLoS Medicine 09/2015; 10(8). DOI:10.1371/journal.pone.0135327 · 14.43 Impact Factor
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    ABSTRACT: Aim: The aim of the study was to compare the differences between patient global disease activity (PtGDA) and physician global disease activity (PhGDA) score within and across 13 countries in the METEOR (Measurement of Efficacy of Treatment in the "Era of Outcome" in Rheumatology) database. Methods: Data from METEOR were used to compare PtGDA and PhGDA, scored independently on a 100-mm visual analog scale from 0 (best possible) until 100 (worst possible), in 23,117 visits in 5709 anonymized patients during the period between 2008 and 2012. Linear mixed models were used to model mean differences between PtGDA and PhGDA in 13 countries (Brazil, Czech Republic, France, Ireland, Italy, Latvia, Mexico, the Netherlands, Pakistan, Portugal, Spain, United Kingdom, and the United States), adjusted for differences in Disease Activity Score in 28 joints (DAS28). Generalized estimating equations were used to model differences (>20 mm) between PtGDA and PhGDA score as the outcome and countries as determinants, adjusted for DAS28. Results: Mean difference between PtGDA and PhGDA scores varied by country, from -2 mm (physician scores higher) in Mexico to +14 mm (patient scores higher) in Brazil. "Country" was a significant determinant of the difference between PtGDA and PhGDA scores, independent of differences in DAS28. With the Netherlands as reference, PtGDA and PhGDA scores for individual patients differ significantly in almost all (n = 10) countries, with the exception of France and Spain. Conclusions: Differences between patients' and physicians' assessment of GDA vary across the countries. Influence of country must be taken into account when interpreting discordances between the patient's and the physician's assessment of GDA in rheumatoid arthritis.
    Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 09/2015; 21(7):349-354. DOI:10.1097/RHU.0000000000000296 · 1.08 Impact Factor
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    ABSTRACT: Chronic back pain (CBP) is frequently the presenting symptom in patients with suspected axial spondyloarthritis (axSpA). Presence of sacroiliitis on magnetic-resonance-imaging (MRI) or HLA-B27 adds to diagnostic certainty. However, these costly tests cannot be applied in all patients with CBP. This study aims to investigate which SpA features increase the likelihood of a positive HLA-B27 or positive MRI of the sacroiliac-joints (MRI-SI) in patients with suspected axSpA. Data from 665 patients with CBP within the ESPeranza Programme were analysed. Diagnostic utility measures (LR+, LR−) for a positive MRI-SI or HLA-B27 were calculated for various definitions of inflammatory back pain (IBP), their separate items and for other SpA features. Pretest probabilityies of a positive result was 41 % for MRI-SI and 40 % for HLA-B27. For a positive MRI-SI result the most useful IBP characteristic was alternating buttock pain (LR + =2.6). Among the IBP-criteria, fulfillment of the ‘ASAS criteria’ (LR + =2.1) was most contributory. Interestingly, the addition of alternating buttock pain to the Calin/ASAS-IBP criteria (LR + =6.0 and 5.5, respectively) or the addition of awakening at second half of night to the Calin-IBP criteria (LR + =5.5) increased the pre-test probability of MRI-sacroiliitis from 41 % to 79–80 %. Dactylitis (LR + =4.1) and inflammatory bowel disease (IBD) (LR + =6.4) increased this probability to 73 % and 81 %, respectively. To forecast HLA-B27 positivity, awakening at the second half of the night, fulfillment of the ASAS-IBP definition and uveitis were the most useful, but only marginally predictive (LR + = 1.3, 1,6 and 2.6, respectively). If patients with suspected axial SpA have either 1) IBP according to Calin/ASAS definition plus alternating buttock pain, or 2) IBP according to Calin definition plus awakening at night, or 3) dactylitis or 4) IBD, the probability of finding a positive MRI-SI increases significantly.
    Arthritis research & therapy 09/2015; 17(1):265. DOI:10.1186/s13075-015-0779-y · 3.75 Impact Factor
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    ABSTRACT: As patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA. Patients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers. In the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4–15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was −3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128. In patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years. Trial registration ClinicalTrials.gov, NCT00160602 and NCT00160641. Registered 8 September 2005.
    Arthritis Research & Therapy 09/2015; 17(1). DOI:10.1186/s13075-015-0767-2 · 3.75 Impact Factor
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    ABSTRACT: Objectives: To investigate the complex relationship between inflammation, mechanical stress and radiographic progression in patients with ankylosing spondylitis (AS), using job type as a proxy for continuous mechanical stress. Methods: Patients from the Outcome in Ankylosing Spondylitis International Study were followed up for 12 years, with 2-yearly assessments. Two readers independently scored the X-rays according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Disease activity was assessed by the AS Disease Activity Score C reactive protein (ASDAS-CRP). The relationship between ASDAS and spinal radiographic progression was investigated with longitudinal analysis, with job type at baseline (physically demanding ('blue-collar') versus sedentary ('white-collar') labour) as a potential factor influencing this relationship. The effects of smoking status and socioeconomic factors were also investigated. Results: In total, 184 patients were included in the analyses (70% males, 83% human leucocyte antigen-B27 positive, 39% smokers, 48% blue-collar workers (65/136 patients in whom data on job type were available)). The relationship between disease activity and radiographic progression was significantly and independently modified by job type: In 'blue-collar' workers versus 'white-collar' workers, every additional unit of ASDAS resulted in an increase of 1.2 versus 0.2 mSASSS-units/2-years (p=0.014 for the difference between blue-collar and white-collar workers). In smokers versus non-smokers, every additional unit of ASDAS resulted in an increase of 1.9 versus 0.4 mSASSS-units/2-years. Conclusions: Physically demanding jobs may amplify the potentiating effects of inflammation on bone formation in AS. Smoking and socioeconomic factors most likely confound this relationship and may have separate effects on bone formation.
    09/2015; 1(1):e000153. DOI:10.1136/rmdopen-2015-000153
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    ABSTRACT: Objectives: To investigate the prevalence of comorbidities in early rheumatoid arthritis (ERA) and early axial spondyloarthritis (ESpA) versus the general population. Methods: Baseline data of 689 patients with ERA from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (age 48.2±12.1 years, symptoms duration 14.2±14.5 weeks) and 645 patients with ESpA from Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; age 32.8±8.4 years, axial symptoms duration 79.0±45.7 weeks) were analysed. Metabolic and cardiovascular diseases (CVD), infections and neoplasia were determined in each cohort. The prevalence (95% CI) of several comorbidities was compared with that in the French general population. For patients without CVD, the 10-year risk of developing CVD was calculated using the Framingham and SCORE equations. The heart age was calculated using the 2008 Framingham points system. Results: 42% of patients with ERA and 20.3% of patients with ESpA had at least 1 comorbidity; the most common were arterial hypertension (AHT) and dyslipidaemia. AHT prevalence (95% CI) in ERA (18.2% (15.5% to 21.3%)), but not in ESpA (5.08% (3.57% to 7.14%)), was significantly increased (p<0.05) compared with the general population (7.58%). Prevalence of tuberculosis history was higher in ERA (4.7% (3.3% to 6.6%)), and ESpA (0.99% (0.4% to 2.3%)) than in the general population (0.02%; both p<0.05). No differences were observed in malignancies, coronary heart disease or diabetes. In ERA, among patients without a history of CVD, an intermediate to high CVD risk was found. The heart age exceeded the real age by 4.1±9.6 years in ERA and by 2.1±7.0 years in ESpA (p<0.001). Conclusions: We found an increased prevalence of AHT and tuberculosis history in ERA and ESpA, and an increased CVD risk. These results should prompt rheumatologists to check these comorbidities early in the disease.
    09/2015; 1(1):e000128. DOI:10.1136/rmdopen-2015-000128
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    Désirée van der Heijde · Avani Joshi · Aileen L Pangan · Naijun Chen · Keith Betts · Manish Mittal · Yanjun Bao ·
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    ABSTRACT: To assess the impact of achieving Assessment in SpondyloArthritis international Society 40% (ASAS40) response or an Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID) state on patient-reported outcomes (PROs) among patients with non-radiographic axial SpA (nr-axSpA). Data are from ABILITY-1, a phase 3 trial of adalimumab vs placebo in nr-axSpA patients. PROs included the HAQ for Spondyloarthropathies (HAQ-S), 36-item Short Form Health Survey (SF-36) physical component summary (PCS) score and Work Productivity and Activity Impairment Questionnaire. Patients were grouped by clinical response using ASAS40 response and ASDAS disease states at week 12. Changes in PROs from baseline to week 12 were compared between groups using analysis of covariance with adjustment for baseline scores. At week 12, 47 of 179 patients were ASAS40 responders and 26 of 176 patients achieved ASDAS-ID (ASDAS <1.3). Compared with non-responders (n = 132), ASAS40 responders (n = 47) had a significantly greater improvement in mean HAQ-S (-0.65 vs -0.05, P < 0.0001), SF-36 PCS (12.4 vs 0.7, P < 0.0001), presenteeism (-24.7 vs -2.2, P < 0.0001), overall work impairment (-23.9 vs -2.5, P < 0.0001) and activity impairment (-33.5 vs -0.9, P < 0.0001) at week 12. Similarly, ASDAS-ID, ASDAS clinically important improvement (ASDAS-CII; improvement >1.1) and major improvement (ASDAS-MI; improvement >2.0) were associated with significantly greater improvements from baseline in the majority of the PROs. Among nr-axSpA patients, ASAS40, ASDAS-CII and ASDAS-MI response and achievement of ASDAS-ID were associated with statistically significant and clinically meaningful improvements in physical function, health-related quality of life and work productivity in a higher percentage of patients. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
    Rheumatology (Oxford, England) 08/2015; DOI:10.1093/rheumatology/kev267 · 4.48 Impact Factor
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    ABSTRACT: Objectives: To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors. Methods: The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls. Results: Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10-9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels. Conclusions: DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.
    PLoS ONE 08/2015; 10(8):e0134974. DOI:10.1371/journal.pone.0134974 · 3.23 Impact Factor
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    ABSTRACT: Objectives: To investigate the extent and performance of MRI lesions in the sacroiliac joint (MRI-SI) and spine (MRI-spine) in patients with suspected axial spondyloarthritis (axSpA). Methods: MRI-SI/spine of patients with chronic back pain (onset <45 years) in the SPondyloArthritis Caught Early (SPACE) cohort were scored by two well-trained readers for inflammation, fatty lesions, erosions, sclerosis/ankylosis and syndesmophytes. MRI performances were tested against the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria (positive: imaging-arm+ or clinical-arm+; negative: possible axSpA (few spondyloarthritis (SpA) features present) or no SpA). Arbitrary cut-off levels for MRI lesions were set to assure at least 95% specificity (tested in the no SpA group). Results: In total 126 patients were ASAS criteria positive (73 imaging-arm+ (22 by modified New York criteria (mNY)+; 51 by MRI+mNY-); 53 clinical-arm+) and 161 were ASAS criteria negative (89 possible axSpA and 72 no SpA). On MRI-SI (n=287), at least three fatty lesions (or at least three erosions) were seen in 45.5 (63.6)% of mNY+ patients, 15.7 (47.1)% of MRI+mNY- patients and 15.1 (13.2)% of clinical-arm+ patients versus 3.4 (6.7)% of possible axSpA patients and 2.8 (4.2)% of no SpA patients. A combined rule (at least five fatty lesions and/or erosions) performed equally well. Sclerosis and ankylosis were too rare to analyse. On MRI-spine (n=284), at least five inflammatory lesions (or at least five fatty lesions) were seen in 27.3 (18.2)% of mNY+ patients, 13.7 (21.6)% of MRI+mNY- patients and 3.8 (1.9)% of clinical-arm+ patients versus 4.5 (6.7)% of possible SpA patients and 2.9 (4.3)% of no SpA patients. Conclusions: The presence of (1) at least five fatty lesions and/or erosions on MRI-SI, (2) at least five inflammatory lesions or (3) at least five fatty lesions on MRI-spine allows an acceptable discrimination of axSpA and no SpA, while assuring >95% specificity.
    Annals of the rheumatic diseases 08/2015; DOI:10.1136/annrheumdis-2015-207823 · 10.38 Impact Factor
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    ABSTRACT: Objectives: To determine the prevalence of degenerative changes (DCs) in the spine of young patients with back pain without axial spondyloarthritis (no-axSpA), with possible axSpA (poss-axSpA) and with definite axSpA (axSpA), as shown on MRI and radiographs. Methods: Whole-spine MRI and cervical and lumbar radiography were performed in patients ≥16 years of age with chronic back pain (≥3 months, ≤2 years, onset <45 years) and potential axSpA (Spondyloarthritis Caught Early cohort). Patients were classified as no-axSpA, poss-axSpA [not fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria] or axSpA (fulfilling ASAS axSpA criteria). Images (MRI and X-rays) were evaluated on the presence of DCs by two independent readers, blinded to clinical and laboratory information as well as to the results of the other imaging modality. In cases of disagreement, a third reader served as adjudicator. A Chi-square test was used to analyse differences between patient groups according to various selected cut-off points (1-3) of individual DCs. Results: Of 274 patients (38% male, mean age: 29 years), 25 (9%) were classified as no-axSpA, 134 (48.9%) as poss-axSpA and 115 (42.0%) as axSpA. Two hundred and forty-five (89%) patients had DCs on MRI [21/25 (84%) no-axSpA, 121/134 (90%) poss-axSpA, 103/115 (90%) axSpA, P = 0.792], range 1-29 (median 5.5), and 121 (44%) patients had DCs on radiographs [13/25 (52%) no-axSpA, 62/134 (46%) poss-axSpA, 48/115 (42%) axSpA, P = 0.261], range 1-11 (median 2). Prevalence of DCs was similar between patient groups. DCs were predominantly found in the lumbar spine. Conclusion: Prevalence of DCs was high in this cohort of young patients with short-term chronic back pain, in accordance with the literature. Prevalence of DCs in no-axSpA patients, poss-axSpA patients and axSpA patients was found to be similar.
    Rheumatology (Oxford, England) 08/2015; DOI:10.1093/rheumatology/kev283 · 4.48 Impact Factor

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23k Citations
3,218.55 Total Impact Points


  • 2015
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 2008-2015
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2007-2015
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo, Norway
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2014
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
    • Oregon Health and Science University
      Portland, Oregon, United States
    • Mount Sinai Hospital, Toronto
      Toronto, Ontario, Canada
  • 2013
    • Novartis Institutes for BioMedical Research
      Cambridge, Massachusetts, United States
  • 2012
    • Laval University
      Quebec City, Quebec, Canada
    • University of Leeds
      • Section of Clinical Musculoskeletal Disease
      Leeds, England, United Kingdom
  • 1995-2011
    • Maastricht University
      • Department of Internal Medicine
      Maestricht, Limburg, Netherlands
  • 1997-2009
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2004
    • Carol Davila University of Medicine and Pharmacy
      • Department of Internal Medicine and Rheumatology
      Bucharest, Bucuresti, Romania
  • 2001
    • Boston University
      Boston, Massachusetts, United States
  • 1992
    • University of Groningen
      • Department of Statistics
      Groningen, Groningen, Netherlands
  • 1989
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands