Publications (49)177.77 Total impact

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    ABSTRACT: We aimed to assess the association of the degree of radiologic damage at baseline with long-term patient-related outcomes (PRO) in patients with severe rheumatoid arthritis (RA). This prospective observational single-centre study (Ratingen, Germany) included all RA patients starting treatment with methotrexate (MTX) between 1980 and 1987. Standardised clinical evaluations and radiographs of hands and feet were obtained at baseline and during the following years. About 18 years later, patients were invited for a re-assessment. PRO were assessed in three dimensions according to the International Classification of Functioning and Disability (ICF). Statistical analyses comprised multivariable models using baseline values for radiologic damage of hands and feet, age, gender, disease duration, rheumatoid factor positivity, measures of disease activity, and response to MTX as covariates. At baseline, the mean disease duration was 8.5 years. The disease was active with a mean number of swollen joints of 18 (out of 32) and a mean erythrocyte sedimentation rate of 55 mm/hour. Radiologic damage was present in 95% of the patients. After 18 years, patient-related outcomes could be assessed in 78/271 patients (29%). Among chosen covariates, only the degree of baseline radiologic damage as measured by the Ratingen score was predictive of all long-term PRO (p<0.016). In this cohort including patients with severe RA, baseline radiologic damage was a good long-term predictor of PRO related to all three ICF dimensions.
    No preview · Article · Aug 2015 · Clinical and experimental rheumatology
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    ABSTRACT: Methotrexate (MTX) is the anchor drug in the treatment of patients with rheumatoid arthritis (RA). MTX shows effects on disease activity and mortality. However, it is unclear whether the effect of MTX on mortality depends on its effect on disease activity. In a post-hoc analysis we analysed the data of our cohort established in Ratingen, Germany, and included all patients starting treatment with MTX (n=271) between 1980 and 1987. One year after baseline (BL), response to MTX treatment was assessed using a modified ACR 20 response. Follow-up data of 250 patients were available after 10 and 18 years. After 1 year, there were 66% responders and 20% non-responders; only 14% had discontinued MTX treatment due to side effects or lack of efficacy. Most patients continued MTX treatment irrespective of efficacy. Ten years after BL, 61% of the patients were still treated with MTX. After 18 years, the responder-group showed a standardised mortality ratio of 1.6 compared to 3.2 for the group of non-responders. However, when adjusting for age, gender, response to MTX treatment one year after BL, number of swollen joints and comorbidities after 10 years an independent association of continued MTX treatment with lower mortality was found for the period 10 to 18 years after BL (hazard ratio (HR): 0.63, 95% confidence interval: 0.43-0.92, p=0.015). In this cohort, the mortality lowering effect of continued MTX use was partly independent of its effect on disease activity. This finding may affect treatment decisions concerning RA patients with insufficient response to MTX.
    No preview · Article · Apr 2014 · Clinical and experimental rheumatology
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    ABSTRACT: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
    Full-text · Article · Nov 2010 · Clinical and experimental rheumatology

  • No preview · Article · Jun 2010 · Annals of the rheumatic diseases
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    ABSTRACT: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 <or=3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.
    Full-text · Article · Nov 2007 · Annals of the Rheumatic Diseases

  • No preview · Article · Jun 2007 · Annals of the rheumatic diseases
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    ABSTRACT: The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse' (78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All 22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers applying the van der Heijde-modified Sharp scoring method and was reflected in their scores.
    Full-text · Article · Feb 2007 · Arthritis research & therapy

  • No preview · Article · Jun 2006 · Annals of the rheumatic diseases

  • No preview · Conference Paper · Jun 2006
  • Yebin Jiang · Harry Kenneth Genant · Gertraud Herborn · John T Sharp · Fan Li
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    ABSTRACT: PURPOSE Recent advances in molecular engineering and improvements in understanding the pathophysiology of arthritic disorders have resulted an unprecedented number of new therapeutic agents being submitted for clinical testing. Imaging is needed to identify appropriate subjects for clinical studies and to monitor disease progression, treatment response, and complications of disease or therapy. We compared the reproducibility and agreements of semiquantitative scoring of erosion (E), joint space narrowing (J), and their combination (T) in the hands of patients with rheumatoid arthritis (RA), using laser-digitized images on high-resolution monitors from a PACS versus the original radiographs. METHOD AND MATERIALS Hand radiographs of 60 patients were obtained at 2 visits (baseline, 6 to 24 months follow-up), digitized at 100 and 50 �m pixel sizes, blinded to sequence, and independently scored by 3 experienced readers using the Genant or Sharp methods. RESULTS Inter-technique intra-reader intraclass correlation coefficients (ICCs) for each of the two visits were 0.94-0.99 E, 0.91-0.95 J, and 0.90-0.97 T; and 0.95-0.99 E, 0.88-0.97 J, and 0.95-0.98 T for progression between the two visits. Intra-technique intra-reader ICCs were 0.96-0.99 E, 0.89-0.95 J, and 0.93-0.97 T for the two visits; and 0.94-0.99 E, 0.90-0.96 J, and 0.93-0.97 T for progression. Intra-technique inter-reader ICCs were 0.81-0.93 E, 0.70-0.79 J, and 0.80-0.86 T for the two visits; and 0.92-0.96 E, 0.89-0.92 J, and 0.91-0.93 T for progression. Inter-technique intra-reader ICCs for new lesions in intact joints at baseline were 0.89-0.98. Over all, the Genant and the Sharp methods showed similar reproducibility and close correspondence. CONCLUSIONS Scoring ERO, JSN, and Total, either at one time point or serially, using different scoring methods, of digitized images produces high inter- and intra-reader and inter- and intra -technique reproducibility that is equal to and provides results very close to that of the original radiographs. This technique seems robust and may be useful in centralized radiographic assessment in multi-center epidemiological studies of RA, or in clinical studies evaluating the therapeutic efficacy of antirheumatic agents.
    No preview · Conference Paper · Nov 2004
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    R Rau · G Herborn · S Wassenberg
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    ABSTRACT: This is an overview over the history and present state of knowledge of radiographic signs of erosion healing. The existence of healing or repair has been confirmed; different observers agree in the identification of healing; it may be identified without knowing the sequence of the films. As healing indicates that inflammation has discontinued for several months in an individual joint, it might represent a good additional outcome measure in RA clinical trials.
    Full-text · Article · Sep 2004 · Clinical and experimental rheumatology
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    R Rau · G Herborn
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    ABSTRACT: This is a literature review on the efficacy and toxicity of low dose weekly methotrexate treatment in rheumatoid arthritis. Personal recommendations on dosing and monitoring (of) the drug are given.
    Preview · Article · Sep 2004 · Clinical and experimental rheumatology
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    ABSTRACT: The genetic background of rheumatoid arthritis (RA) is only partly understood, and several genes seem to be involved. The matrix metalloproteinases MMP1 (interstitial collagenase) and MMP3 (stromelysin 1) are thought to be important in destructive joint changes seen in RA. In the present study, functional relevant promoter polymorphisms of MMP1 and MMP3 were genotyped in 308 patients and in 110 controls, to test whether the polymorphisms contribute to the severity of the disease measured by radiographic progression of joint destruction. For comparison, the shared epitope of HLA DR4 and DR1 (SE) was determined by polymerase chain reaction. There was no association of MMP polymorphisms with susceptibility to RA. However, a strong linkage disequilibrium was observed between the 1G/2G (MMP1) and the 5A/6A (MMP3) polymorphisms (P < 10(-6); linkage disequilibrium index D' = 0.46). In factorial regression, the degree of radiographic joint destruction correlated significantly with the 1G-5A haplotype (P = 0.0001) and the interaction term 'estimated number of 1G-5A haplotypes x duration of disease' (P = 0.0007). This association was phasic, indicating that possession of the 1G-5A haplotype has a protective effect over a period of about 15 years of RA, but might be associated with a more pronounced radiographic progression later on. Similar results were also found with the 1G allele of MMP1 alone (P = 0.015) and with the interaction term 'estimated number of 1G alleles x duration of disease' (P = 0.014). The correlation of SE with the Ratingen score was comparable (0.044). The regression model of MMP haplotypes explained 35% of the variance of the radiographic score, whereas the SE explained 29%. The 1G-5A haplotype across the closely linked MMP1 and MMP3 gene loci is a newly described genetic factor strongly associated with the progression of joint damage in RA. Our findings suggest that there are haplotypes in a MMP cluster region that modify the joint destruction in RA in a phasic manner.
    Full-text · Article · Feb 2004 · Arthritis research & therapy
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    ABSTRACT: The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.
    Full-text · Article · Jun 2003 · The Journal of Rheumatology
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    R Rau · G Herborn · H Fenner

    Full-text · Article · Feb 2003 · Arthritis & Rheumatology
  • R Rau · G Herborn · H Menninger · O Sangha
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    ABSTRACT: To compare the radiographic outcomes after 36 months in patients with early erosive rheumatoid arthritis (RA) who were treated with methotrexate (MTX) or gold sodium thiomalate (GSTM). In a randomized, double-blind fashion, 174 patients from two centres were assigned to receive weekly intramuscular injections of either 15 mg MTX or 50 mg GSTM. After 12 months, the study was continued as an open prospective study for an additional 2 yr, administering the same amount of MTX and half of the GSTM dose. Radiographic outcomes were assessed by standardized methods in all patients at baseline and after 6, 12, 24 and 36 months. Intention-to-treat analysis showed that patients treated with MTX had higher radiographic scores and more erosive joints at all follow-up points. However, there was no statistically significant difference between the two treatment groups. The progression rate was significantly slower during the second and third years of follow-up in both groups. Baseline and time-integrated (area under the curve over 6 months) disease activity parameters were good predictors of radiographic outcome after 3 yr. Seropositivity was not an independent predictor of progression. However, patients who were positive for rheumatoid factor had higher time-integrated disease activity (with less response to treatment) and thus their disease was significantly more progressive. Both of the disease-modifying compounds used in this study, MTX and GSTM, were able to reduce the slope of radiographic progression during 3 yr of follow-up. There was some advantage for parenteral gold but no significant intergroup difference.
    No preview · Article · Mar 2002 · Rheumatology
  • R Rau · S Wassenberg · G Herborn · W T Perschel · G Freitag
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    ABSTRACT: Conventional radiographic scoring methods in rheumatoid arthritis (RA) are designed to quantify progression and disregard any improvement. Reparative changes observed during longterm followup of RA have rarely been described as healing phenomena. Healing may become increasingly important with the availability of more potent antirheumatic drugs. We investigated whether radiologic healing phenomena can be identified by different observers in a blinded fashion. Healing phenomena were defined as (1) reappearance (and sclerosis) of the cortical plate, (2) partial or complete filling in of an erosion, or (3) subchondral bone sclerosis with osteophyte formation (secondary osteoarthritis). Pairs of radiographs of hands, wrists, and forefeet [taken 2 to 8 (mean 4.8) yrs apart] of 34 patients were selected from longterm studies: 24 sets with healing phenomena and 10 with progressive disease without healing. The radiographs were blinded and read in pairs in random order by 3 observers unaware of the patients selected for the study. One observer read the set a second time after 8 weeks, resulting in a total of 4 observations. Thirty-eight joints were rated 0 to 5 depending on the amount of surface destruction. In addition an attempt was made to identify joints with healing phenomena. The data were analyzed with help of descriptive statistics such as means, standard deviations, and frequency tables. Out of 1292 joints scored at the second time point, 74 had healing phenomena. These joints were identified in a mean of 89% (95/89/88/82%, respectively) in the 4 observations performed by the 3 readers. Patients without healing phenomena were correctly identified by all observers. In 54 joints less typical healing phenomena were seen in all observations. Sixty-two joints with healing in addition to the 74 joints were seen in 3 observations, 76 in 2, and 127 in one observation. All observers agreed that 1090 joints had no healing phenomenon. The 24 patients with healing had a slight reduction in the Ratingen score, while the 10 patients without healing showed a moderate progression. In the group with healing an increase and decrease in the score occurred in the same patients at different joints. In patients with RA followed for several years healing or reparative changes of erosions can be observed. These phenomena can be identified by different observers with high sensitivity even when the observers are blinded to chronological sequence of the films.
    No preview · Article · Jan 2002 · The Journal of Rheumatology
  • S Wassenberg · V Fischer-Kahle · G Herborn · R Rau
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    ABSTRACT: Radiographic features of psoriatic arthritis (PsA) are very characteristic and differ from those observed in rheumatoid arthritis, especially in two aspects: 1) the distribution of affected joints (i.e. DIP joints), 2) the presence of destructive changes and bone proliferation at the same time. A scoring method for PsA, therefore, has to account for these characteristics of PsA. To develop, describe and validate a method for scoring radiographic changes in patients with PsA. DESCRIPTION OF THE METHOD: Forty joints of the hands and feet are scored for destruction and proliferation. In the destruction score (DS) grading on a 0-5 scale is based on the amount of joint surface destruction: 0 = normal, 1 = one or more erosions with an interruption of the cortical plate of > 1 mm with destruction of the total joint surface up to 10%, 2 = 11-25%, 3 = 26-50%, 4 = 51-75%, 5 = > 75% joint surface destruction. The proliferation score (PS) sums up any kind of bony proliferation typical for PsA; graded 0-4: 0 = normal, 1 = bony proliferation of 1-2 mm or bone growth < 25% of the original size (diameter), 2 = bony proliferation 2-3 mm or bone growth 25-50%, 3 = bony proliferation > 3 mm or bone growth > 50%, 4 = bony ankylosis. The DS (0-200) and the PS (0-160) can be summed up to the total score (0-360). VALIDATION OF THE METHOD: To validate the method x-rays of 20 patients with active PsA taken 3 years apart were read twice in pairs, knowing the chronological order but not knowing demographic, clinical or laboratory data of the patients. The data were analyzed with a hierarchical analysis of variance model. There was good agreement between the first and the second reading of the same rater and between the two raters regarding the destruction score. The agreement regarding the proliferation score was lower but still acceptable. The reliability of the method to describe change over time--relation of progression (intra-patient variance) to the measurement error (inter-rater variance)--was 3.9 for the DS, 2.8 for the PS and 4.1 for the total score. The minimal detectable change when the readings of two raters were compared (inter-rater MDC) was 5.8, 5.0 and 4.6%, respectively of the maximum possible score for the destruction, the proliferation and the total score. These data compare very well with the results of standard scoring methods in rheumatoid arthritis. We propose a method for scoring radiographic change in psoriatic arthritis which reliably quantifies the progression of the disease seen on radiographs.
    No preview · Article · Jul 2001 · Zeitschrift für Rheumatologie
  • R Rau · G Herborn · H Fenner

    No preview · Article · Jan 2001 · Rheumatology
  • R Rau · G Herborn · S Zueger · H Fenner
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    ABSTRACT: To investigate the relationship between radiographic disease progression in the presence or absence of rheumatoid arthritis (RA) linked HLA-DRB1 alleles after early introduction of disease modifying antirheumatic drug therapy in patients with RA over a study period of 6 years. One hundred nine patients of a trial comparing intramuscular (im) gold sodium thiomalate (GSTM) and im methotrexate (MTX) in early erosive RA were followed for 6 years with regular assessments of clinical and laboratory data and yearly radiographs of hands and feet, and they were typed for HLA-DRB1 genes. Radiographic progression was analyzed for an influence of rheumatoid factor (RF) status and HLA-DRB1 genes. Twenty-seven patients (25%) were positive for two, 46 (42%) for one, and 36 (33%) for none of the disease linked alleles. A decrease of the rate of radiographic disease progression with treatment in this group of patients was reflected by the decline in the slope of the radiographic score. Seropositive patients (n = 71, 68%) had a significantly more destructive disease course than RF negative patients. In seropositive disease, patients with a "double dose" of RA linked alleles showed a tendency to greater progression during the first 12-24 mo of treatment, but no significant difference in the longterm radiographic outcome could be detected between subgroups defined by the presence or absence of HLA-DRB1 genes. There was no significant difference throughout the study period with respect to the clinical disease course as assessed by joint swelling, C-reactive protein, and erythrocyte sedimentation rate. The majority of the seronegative population (n = 38, 32%) had a benign disease course with the exception of patients (n = 6) with the double allele; they had radiographic disease progression comparable with the seropositive patients. Our data do not provide evidence for a more aggressive disease course in patients bearing double RA linked HLA-DRB1 alleles.
    No preview · Article · Dec 2000 · The Journal of Rheumatology