Désirée van der Heijde

Leiden University, Leyden, South Holland, Netherlands

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Publications (876)6112 Total impact

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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: Objective: To understand the impact of ankylosing spondylitis (AS) on work disability (WD) over 12 years compared with the general population, and explore factors predicting adverse work outcome, defined as new (partial) work disability (WD) or reduction in working hours. Methods: Source of data was the Outcome in AS International Study (OASIS), which includes patients from the Netherlands, France and Belgium. Standardized WD rates over time compared to the general population were calculated using indirect standardization (Dutch patients only). Cox survival analyses identified baseline predictors as well as time-varying factors influencing adverse work outcome over 12 years. Results: Of 215 patients, 55 (26%) were full-WD at baseline and 139 (65%) were at risk for adverse work outcome during follow-up. When compared to the general population, work disability over 12 years continued to be increased in Dutch males (Incidence Rate (IR):2.9 (95%CI:1.2;4.6)), but less clearly females (IR:1.2 (95%CI:-0.4;2.9)). Within the entire sample, baseline predictors of adverse work outcome over 12 years were residence in the Netherlands (vs.France/Belgium) (Hazard Rate (HR):3.4; [95%CI:1.4-8.4]) and worse Bath AS Functional Index (BASFI) (HR)1.2; [95%CI:1.0-1.4]). Time-varying predictors over 12 years were residence in the Netherlands, uveitis and either BASFI or Bath AS Disease Activity (BASDAI) with age and inflammatory bowel disease. Conclusions: Although WD was already prevalent at inclusion in the cohort, a substantial proportion of patients incurred further adverse work outcome over 12 years. In addition to country of residence, uveitis, age and self-reported physical function or disease activity predicted long-term adverse work outcome. This article is protected by copyright. All rights reserved.
    09/2015; DOI:10.1002/acr.22730
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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: Introduction: 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. Methods: 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. Results: 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). Conclusions: 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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    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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    ABSTRACT: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. NCT01258738. 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 08/2015; DOI:10.1136/annrheumdis-2015-207596 · 10.38 Impact Factor
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    ABSTRACT: Anti-tumor necrosis factor agents (anti-TNFs) are frequently used in combination with methotrexate to treat rheumatoid arthritis (RA). We investigated the effect of background methotrexate dose, in combination with anti-TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. A pre-specified subgroup analysis comparing two methotrexate dose categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials RAPID1 (NCT00152386) and RAPID2 (NCT00160602) according to treatment group: CZP 200 mg, CZP 400 mg or placebo, every two weeks. Inclusion criteria required methotrexate dose ≥10 mg/week. Efficacy endpoints included Week 24 ACR20/50/70 responses analyzed by logistic regression, and changes from baseline in DAS28(ESR) and van der Heijde modified Total Sharp Score (mTSS) analyzed by ANCOVA. Incidence rates of treatment-emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post-hoc sensitivity analysis investigated three methotrexate dose categories: ≤10 mg/week; >10 and ≤15 mg/week; and >15 mg/week. 638, 635 and 325 patients received CZP 200 mg, CZP 400 mg and placebo, respectively. At Week 24, treatment responses in both CZP groups were uninfluenced by baseline methotrexate dose category, and were superior to placebo group, for all investigated endpoints: ACR20/50/70, DAS28(ESR) and mTSS. TEAE incidence rates were higher in patients receiving methotrexate ≥15 mg/week for most TEAE types, across treatment groups. CZP efficacy was not affected by background methotrexate dose category. It can be hypothesized that to minimize TEAEs, background methotrexate doses could be tailored to individual patient tolerance without affecting CZP efficacy. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    08/2015; DOI:10.1002/acr.22676
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    ABSTRACT: This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.Genes and Immunity advance online publication, 30 July 2015; doi:10.1038/gene.2015.24.
    Genes and immunity 07/2015; DOI:10.1038/gene.2015.24 · 2.91 Impact Factor
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    ABSTRACT: Background: Axial spondyloarthritis (axSpA) comprises ankylosing spondylitis (radiographic axSpA) and non-radiographic (nr-)axSpA and is associated with psoriasis, uveitis and inflammatory bowel disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment. Objectives: To determine the benefits and harms of NSAIDs in axSpA. Search methods: We searched CENTRAL, MEDLINE and EMBASE to 18 June 2014. Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs of NSAIDs versus placebo or any comparator in adults with axSpA and observational cohort studies studying the long term effect (≥ six months) of NSAIDs on radiographic progression or adverse events (AEs). The main comparions were traditional or COX-2 NSAIDs versus placebo. The major outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), radiographic progression, number of withdrawals due to AEs and number of serious AEs Data collection and analysis: Two review authors independently selected trials for inclusion, assessed the risk of bias, extracted data and assessed the quality of evidence for major outcomes using GRADE. Main results: We included 39 studies (35 RCTs, two quasi-RCTs and two cohort studies); and 29 RCTs and two quasi-RCTs (n = 4356) in quantitative analyses for the comparisons: traditional NSAIDs versus placebo, cyclo-oxygenase-2 (COX-2) versus placebo, COX-2 versus traditional NSAIDs, NSAIDs versus NSAIDs, naproxen versus other NSAIDs, low versus high dose. Most trials were at unclear risk of selection bias (n = 29), although blinding of participants and personnel was adequate in 24 trials. Twenty-five trials had low risk of attrition bias and 29 trials had low risk of reporting bias. Risk of bias in both cohort studies was high for study participation, and low or unclear for all other criteria. No trials in the meta-analyses assessed patients with nr-axSpA.Traditional NSAIDs were more beneficial than placebo at six weeks. High quality evidence (four trials, N=850) indicates better pain relief with NSAIDs (pain in control group ranged from 57 to 64 on a 100mm visual analogue scale (VAS) and was 16.5 points lower in the NSAID group (95% confidence interval (CI) -20.8 to -12.2), lower scores indicate less pain, NNT 4 (3 to 6)); moderate quality evidence (one trial, n = 190) indicates improved disease activity with NSAIDs (BASDAI in control group was 54.7 on a 100-point scale and was 17.5 points lower in the NSAID group, 95% CI -23.1 to -11.8), lower scores indicate less disease activity, NNT 3 (2 to 4)); and high quality evidence (two trials, n = 356) indicates improved function with NSAIDs (BASFI in control group was 50.0 on a 100-point scale and was 9.1 points lower in the NSAID group (95% CI -13.0 to -5.1), lower scores indicate better functioning, NNT 5 (3 to 8)). High (five trials, n = 1165) and moderate (three trials, n = 671) quality evidence (downgraded due to potential imprecision) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (52/1000 and 2/1000) and NSAID (39/1000 and 3/1000) groups after 12 weeks (risk ratio (RR) 0.75, 95% CI 0.46 to 1.21; and RR 1.69, 95% CI 0.36 to 7.97, respectively). BASMI and radiographic progression were not reported.COX-2 NSAIDS were also more efficacious than placebo at six weeks. High quality evidence (two trials, n = 349) indicates better pain relief with COX-2 (pain in control group was 64 points and was 21.7 points lower in the COX-2 group (95% CI -35.9 to -7.4), NNT 3 (2 to 24)); moderate quality evidence (one trial, n = 193) indicates improved disease activity with COX-2 (BASDAI in control groups was 54.7 points and was 22 points lower in the COX-2 group (95% CI -27.4 to -16.6), NNT 2 (1 to 3)); and high quality evidence (two trials, n = 349) showed improved function with COX-2 (BASFI in control group was 50.0 points and was 13.4 points lower in the COX-2 group (95% CI -17.4 to -9.5), NNT 3 (2 to 4)). Low and moderate quality evidence (three trials, n = 669) (downgraded due to potential imprecision and heterogeneity) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (11/1000 and 2/1000) and COX-2 (24/1000 and 2/1000) groups after 12 weeks (RR 2.14, 95% CI 0.36 to 12.56; and RR 0.92, 95% CI 0.14 to 6.21, respectively). BASMI and radiographic progression were not reported.There were no significant differences in benefits (pain on VAS: MD -2.62, 95% CI -10.99 to 5.75; three trials, n = 669) or harms (withdrawals due to AEs: RR 1.04, 95% CI 0.60 to 1.82; four trials, n = 995) between NSAID classes. While indomethacin use resulted in significantly more AEs (RR 1.25, 95% CI 1.06 to 1.48; 11 studies, n = 1135), and neurological AEs (RR 2.34, 95% CI 1.32 to 4.14; nine trials, n = 963) than other NSAIDs, these findings were not robust to sensitivity analyses. We found no important differences in harms between naproxen and other NSAIDs (three trials, n = 646), although other NSAIDs appeared more effective for relieving pain (MD 6.80, 95% CI 3.72 to 9.88; two trials, n = 232). We found no clear dose-response effect on benefits or harms (five studies, n = 1136). Single studies suggest NSAIDs may be effective in retarding radiographic progression, especially in certain subgroups of patients, e.g. patients with high CRP, and that this may be best achieved by continuous rather than on-demand use of NSAIDs. Authors' conclusions: High to moderate quality evidence indicates that both traditional and COX-2 NSAIDs are efficacious for treating axSpA, and moderate to low quality evidence indicates harms may not differ from placebo in the short term. Various NSAIDs are equally effective. Continuous NSAID use may reduce radiographic spinal progression, but this requires confirmation.
    Cochrane database of systematic reviews (Online) 07/2015; 7:CD010952. DOI:10.1002/14651858.CD010952.pub2 · 6.03 Impact Factor
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    ABSTRACT: DESIR is a prospective longitudinal multicentric French cohort of patients with inflammatory back pain suggestive of spondyloarthritis, with a 10-year-follow-up. The purpose is to evaluate the performances of the different sets of classification criteria for axial spondyloarthritis, and to describe the frequency and characteristics of the clinical features of axial spondyloarthritis. Demographic data and items allowing classification and indices calculation were collected, as well as biologic and imaging data. Baseline data are analyzed. The performance of the several classification criteria sets was evaluated (likelihood ratio) with the physician's diagnosis as external gold standard. For the clinical presentation of axial spondyloarthritis, a descriptive analysis was conducted. Seven hundred and eight patients are included. Ninety-two percent of them satisfy at least one set of classification criteria: mNY 26%, Amor 79%, ESSG 78%, ASAS 70%; physician's confidence level 6.8±2.7. 81 and 83% of patients fulfil modified (including MRI) Amor or ESSG criteria. Axial involvement is present in 100% of the cases. NSAIDs are taken by 90%, with an NSAID sore of 50±46. BASDAI over 40 is noted in 60% and elevated CRP in 30% of the cases. HLA-B27 is present in 58%. According to ASDAS CRP levels, 12.7% are in inactive disease, 63% in high disease activity; mean BASFI was 30. Peripheral involvement is present in 57%, with arthritis in 37% of these. Enthesitis is noted in 49% of the patients, and first symptom in 22.5%; anterior chest wall involvement is noted in 44.6%, and dactylitis in 13%. For extra articular manifestations, psoriasis is recorded in 16%, uveitis in 8.5% and IBD in 5.1%. Smoking is present in 36.3% and hypertension in 5.1% of the cases. These data represent the base of evaluation of the follow-up of this cohort, allowing future specific studies. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
    Joint, bone, spine: revue du rhumatisme 07/2015; DOI:10.1016/j.jbspin.2015.02.006 · 2.90 Impact Factor
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    ABSTRACT: To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA). 14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3η protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs. Median serum 14-3-3η autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demon-strated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85-0.95). At an optimal cutoff of ≥ 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3η autoantibodies to 14-3-3η protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3η autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF- and ACPA-seronegative patients were positive for 14-3-3η autoantibodies. 14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.
    The Journal of Rheumatology 07/2015; 42(9). DOI:10.3899/jrheum.141385 · 3.19 Impact Factor
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    ABSTRACT: To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. (NCT01451203). 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 07/2015; DOI:10.1136/annrheumdis-2015-207511 · 10.38 Impact Factor
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    ABSTRACT: Background/Purpose Axial spondyloarthritis (axSpA) is a chronic inflammatory disease marked by back pain and stiffness. The objective of this study was to determine if golimumab (GLM) is superior to placebo (PBO) in patients with non-radiographic-axSpA (nr-axSpA). Methods This was a Phase 3, double-blind, randomized, PBO-controlled trial evaluating subcutaneous (SC) GLM 50 mg vs PBO in patients aged ≥18 to ≤45 years with active nr-axSpA according to Assessment of SpondyloArthritis international Society (ASAS) criteria ≤5 years since diagnosis; high disease activity and inadequate response or intolerance to NSAIDs. Patients were randomized 1:1 to GLM or PBO SC every 4 weeks. The primary endpoint was ASAS 20 attainment at week 16. Key secondary endpoints were ASAS 40, ASAS partial remission, BASDAI 50 response, and Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) sacroiliac (SI) joint score. Results Of 198 patients randomized, 197 were treated (GLM=97; PBO=100). Mean age was 31 years; 57% were male. At baseline, mean BASDAI was 6.5 (SD=1.5), ASDAS was 3.5 (SD=0.9), and SPARCC MRI SI was 11.3 (SD=14.0). The primary endpoint, ASAS 20, was achieved by significantly more GLM patients than PBO patients (71.1% vs. 40.0%, respectively p<0.0001). ASAS 40 was also achieved by significantly more GLM patients than PBO (56.7% vs 23.0%, respectively; P<0.0001). The incidence of adverse events did not differ meaningfully between groups. Conclusion Patients with active nr-axSpA treated with GLM had significantly greater improvements in symptoms than patients treated with PBO. GLM was well-tolerated and had a favorable benefit-risk profile. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 07/2015; 74(Suppl 2). DOI:10.1002/art.39257

Publication Stats

33k Citations
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  • 2007–2015
    • Leiden University
      Leyden, South Holland, Netherlands
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo, Norway
  • 2005–2015
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 1995–2015
    • Maastricht University
      • Department of Internal Medicine
      Maestricht, Limburg, 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
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • Novartis Institutes for BioMedical Research
      Cambridge, Massachusetts, United States
  • 2012
    • University of Leeds
      • Section of Clinical Musculoskeletal Disease
      Leeds, England, United Kingdom
    • Laval University
      Quebec City, Quebec, Canada
  • 2011
    • Arthritis Research UK
      Chesterfield, England, United Kingdom
  • 1997–2009
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2008
    • Menzies Research Institute
      Hobart Town, Tasmania, Australia
  • 2004
    • Carol Davila University of Medicine and Pharmacy
      • Department of Internal Medicine and Rheumatology
      Bucharest, Bucuresti, Romania
  • 2003
    • St. Josefs Hospital
      Клоппенбург, Lower Saxony, Germany
  • 2001–2002
    • Stanford University
      • Division of Immunology
      Stanford, CA, United States
    • Boston University
      Boston, Massachusetts, United States
  • 2000
    • Freie Universität Berlin
      • Institute of Social and Cultural Anthropology
      Berlín, Berlin, Germany
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1999
    • St George Hospital
      Sydney, New South Wales, Australia
  • 1989–1992
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands