A Zink

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (217)1012.3 Total impact

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    ABSTRACT: Objective: This observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis. Methods: We investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (≤30 days), and (3) death after SI without known sepsis (≤90 days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously. Results: Sepsis within 30 days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90 days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk. Conclusions: These results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.
    Annals of the Rheumatic Diseases 11/2015; DOI:10.1136/annrheumdis-2015-207838 · 10.38 Impact Factor
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    ABSTRACT: To evaluate the association between exposure to oral contraceptives (OC) and clinical outcomes in an early arthritis cohort. Female patients with early inflammatory arthritis, aged 18 to 60, who were enrolled in an early arthritis cohort and had no exposure to hormone replacement were studied (n=273). Associations between OC exposure (current/past/never) and disease activity, treatment and patient-reported outcomes, including the Rheumatoid Arthritis Impact of Disease Score (RAID), the Rheumatoid Arthritis Disease Activity Index (RADAI), the Profile of Mood and Discomfort (PROFAD) and the Hannover Functional Assessment (FFbH), were studied over 2 years. Linear mixed models adjusted for age, BMI, parity, smoking and education were used. Eighteen percent of patients had never used OCs, 63% had used OCs in the past, and 19% currently used OCs. After adjustment, the current/past OC use was associated with better RAID, PROFAD, RADAI and FFbH scores at 12 months (all p<0.05) compared to never use. Longitudinally over two years, the mean RAID scores were significantly better in women with current/past OC use (p<0.001). Actual inflammatory markers were not associated with OC use. Glucocorticoids were used by a higher percentage of OC never users than by current/past users (p=0.08), especially in patients with impaired function (FFbH<70: OR 4.2 [1.6, 11]). For past as well as current use, OCs seem to moderate patient-reported outcomes in inflammatory arthritis. Protective effects may be induced via central nervous pathways rather than through the suppression of peripheral inflammation. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    08/2015; DOI:10.1002/acr.22667
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    ABSTRACT: Background Polymyalgia rheumatica (PMR) can present alone or with concomitant giant cell arteritis (GCA). They are closely related but implicate different treatment intensity. While PMR is diagnosed clinically, GCA should be confirmed with biopsy or vascular imaging. Objectives To compare patient characteristics, clinical values and treatment of patients with PMR and GCA. Methods Between 2007 and 2013, a total of 1,092 patients with diagnosis of PMR and a disease duration <2 years were recorded in the National Database of the German Collaborative Arthritis Centres. Patients with PMR (ICD-10 M35.3) were compared to patients with GCA in PMR (M31.5) with regard to patient characteristics (age, sex, smoking, BMI, education, comorbidities), markers of inflammation (ESR, CRP), and therapy. Patients aged <50 years (n=8) and with additional inflammatory rheumatic diseases (n=118) were excluded. Results A total of 966 patients with PMR were available for analysis. 820 patients were diagnosed with PMR and 146 patients with GCA. Mean age was 70 years in both groups, mean disease duration 8 vs. 7 months for PMR and GCA, respectively. Patients with GCA were more often female (69% vs. 61%) and more frequently current smokers (21.9% vs. 10.2%). The level of education was similar, as were BMI (26.6 vs. 25.8) and comorbid conditions. 90% of all patients were treated with glucococorticoids. The average dose during the past 6 months was 19.4 mg/d (GCA) vs. 9.2 mg/d. 30% (GCA) vs. 18% were treated additionally with synthetic DMARDs, methotrexate being the most frequently used substance. In a multivariate logistic regression analysis, current smoking remained associated with an increased risk of having GCA (OR=2.8, p=0.005), dominating gender, which was not selected due to its high association with smoking status (p<0.001). Conclusions Compared to PMR alone, patients with GCA present with a higher disease activity and a substantially higher need of immunosuppressive therapy. The association of GCA with current smoking is an additional argument for counselling patients to quit smoking if diagnosed with PMR. Acknowledgements The database was funded by the German Federal Minister of Research from 1999 to 2007 (grant #01 GI 0344/3). Since 2007, the Working Group of the regional corporate arthritis centers and a consortium of pharmaceutical companies has been funding the National Database by an unconditional grant to the German Rheumatological Society. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):322.2-322. DOI:10.1136/annrheumdis-2015-eular.3756 · 10.38 Impact Factor
  • J. Callhoff · K. Albrecht · A. Zink · M. Backhhaus ·

    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):884.2-884. DOI:10.1136/annrheumdis-2015-eular.1781 · 10.38 Impact Factor
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    ABSTRACT: Background Methotrexate (MTX) is the most widely used DMARD in JIA. MTX is regarded to be a safe drug, effective in around 70% of JIA cases. Due to the frequent reoccurrence of disease after discontinuing drug therapy, MTX is often prescribed to patients over an extended period of time. However, little is known about its tolerability in long-term use in JIA. Objectives To determine the frequency of adverse events in JIA patients on MTX and the frequency of drug discontinuation due to MTX intolerance. Methods Patients treated with MTX and prospectively followed in the JIA biologic registers BiKeR and JuMBO were considered for this analysis. Adverse events (AEs) were categorized on the basis of MedDRA. Exposure-adjusted rates for AEs were calculated. MTX intolerance comprised defined preferred terms, representing well-known MTX-induced symptoms, such as nausea, vomiting, and abdominal pain, and direct reports of adverse drug reactions or refusal of MTX. Only events reported by physicians to have at least a possible causal relationship were considered as MTX-related. Results Out of 848 JIA patients followed into adulthood, 725 patients were treated with MTX during the mean observation period of 7.3 years (6,188 patient-years of observation). During this period, patients had been exposed to MTX for a total of 2,762 years (exposure-years [EY]). At enrollment into the register, 687 patients were on MTX (61% of these in combination with a biologic), while at the last follow-up at which patients had a mean age of 21.7 years, only 296 patients were still on MTX (62% in combination with a biologic DMARD). Reasons for MTX discontinuation were provided for 323 cases. MTX was discontinued most frequently because of an AE (39%). Remission was the second most common reason (37%), followed by request from the patient in 22%, inefficacy was the least common reason in 9%. One in three patients received more than one course of MTX, with the first course being the longest with a median treatment duration of 2.6 years (second and third course 1.2 and 1.1 years, respectively). During MTX exposure, 435 AEs (17.7/100 EY) and 50 serious AEs (1.8/100 EY) were considered by the physicians as causally related to MTX. Among these, intolerance dominated with 204 events (7.39/100 EY), followed by infections (n=68, 2.46/100 EY) and hepatotoxicity (n=29, 1.05/100 EY). The frequency of intolerance did not decrease, if patients received further courses of MTX; the exposure-adjusted intolerance rate was 4.3/100 EY during the first MTX course, 11.2, 5.6 and 14.3 during the second, third and fourth course of MTX, respectively. Conclusions These results reflect the major problem of MTX intolerance in the long-term care of JIA patients. Intolerance is the leading cause of MTX discontinuation. Assuming that the request from the patient to stop MTX is related to symptoms experienced during drug exposure, about half of the cases discontinue MTX after almost 3 years due to intolerance. Re-exposure to the drug seems to further increase the intolerance rate of MTX. Acknowledgements BiKeR and JuMBO are funded by unconditional grants from Abbvie, Pfizer, Roche. Disclosure of Interest K. Minden Grant/research support from: Pfizer, Abbvie, Consultant for: Pfizer, Chugai, J. Klotsche: None declared, M. Niewerth: None declared, A. Zink Grant/research support from: AbbVie, BMS, GKS, Medac, MSD, Mundipharma, Roche, Sanofi, Pfizer, UCB, E. Seipelt: None declared, J.-P. Haas Grant/research support from: Pfizer, Novartis, G. Ganser: None declared, G. Horneff Grant/research support from: Pfizer, Abbvie, Roche/Chugai, Consultant for: Pfizer, Chugai
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):609.1-609. DOI:10.1136/annrheumdis-2015-eular.5173 · 10.38 Impact Factor
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    ABSTRACT: Objective: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. Methods: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. Results: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. Conclusion: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.
    Rheumatology 06/2015; 54(6):1074. DOI:10.1093/rheumatology/keu446 · 4.48 Impact Factor

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):70.2-71. DOI:10.1136/annrheumdis-2015-eular.4145 · 10.38 Impact Factor
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    ABSTRACT: Background Three decades ago experimental studies suggested that TNF has a key role in the biological cascade of sepsis [1]. Nevertheless, randomized clinical trials failed to show that TNF inhibition (TNFi) is beneficial for the survival of the patients with sepsis. Objectives To investigate the impact of biological (b)DMARDs regarding the prevention of sepsis and mortality after serious infections (SI) in patients with rheumatoid arthritis. Methods We used data from patients with serious infection (N=859) of the German biologics register RABBIT (Rheumatoid arthritis: observation of biologic therapy). The outcomes of SI: (i) no complication of SI, (ii) sepsis following SI (≤30d), and (iii) death after SI without sepsis (≤90d) were investigated as competing risks. We applied multinomial regression to evaluate the risks of sepsis and death simultaneously (accounting for age, sex, physical function, comorbid heart failure or renal disease, glucocorticoids (GC) and DMARD). Biologics were grouped into TNFi (adalimumab, etanercept, infliximab, golimumab, certolizumab) and other bDMARDs (abatacept, rituximab, tocilizumab). Sensitivity analyses were applied in a subset of patients with pneumonia (N=298) and by restricting the conventional synthetic (cs)DMARD group to biologic naive patients. Generalizability of results was tested by application of bootstrap resampling techniques. Results Sepsis was reported in 135 patients, 53 patients died within 90d after SI without sepsis. At the time of SI, patients treated with bDMARDs were 3.8 years younger (p<0.01) and had fewer cases of chronic renal disease (12 vs. 16%, p>0.13) than patients on csDMARD treatment. There were no differences between DMARD groups in disease duration, DAS28, physical function or frequencies of heart failure. The crude odds ratio (OR) of developing sepsis (bDMARD exposed vs. bDMARD naive) was 0.6 (CI:0.3;0.9). However, 2 out of 3 patients (63%) treated with csDMARDs at SI had discontinued bDMARDs prior to SI. Their risk of sepsis was 2-fold increased (OR: 2.0, CI:1.3; 3.0) compared to continuous bDMARD exposure. The adjusted risk (odds ratio) of developing sepsis increased with age and was higher in patients with chronic renal disease. The risk was significantly lower when patients were exposed to bDMARDs at SI and with better physical function (Table). Risk factors of death after SI were higher age, use of high GC dose and heart failure. The treatment with bDMARDs and better physical function had significant protective effects regarding mortality. Results remained consistent in sensitivity analyses. Conclusions Results suggest that bDMARDs are capable to interfere with the biological pathway from SI to sepsis in a protective manner as already shown by Tracey et al. [1]. The impact of bDMARD discontinuation on the risk of sepsis should be taken into account in treatment decisions. Further investigation is needed to validate these results separately for bacterial and viral SI as well as for each individual bDMARD. References Disclosure of Interest A. Richter Grant/research support from: The German Biologics Register RABBIT is supported by a joint, unconditional grant from AbbVie, Bristol-Myers Squibb, MSD Sharp&Dohme, Pfizer, Roche, and UCB., A. Strangfeld: None declared, M. Schneider: None declared, T. Klopsch: None declared, A. Kapelle: None declared, J. Kaufmann: None declared, A. Zink: None declared, J. Listing: None declared
    Annals of the Rheumatic Diseases; 06/2015
  • K. Albrecht · J. Callhoff · A. Zink · M. Backhaus ·

    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):885.1-885. DOI:10.1136/annrheumdis-2015-eular.1717 · 10.38 Impact Factor
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    ABSTRACT: Objectives To describe changes in drug treatment and clinical outcomes of ankylosing spondylitis (AS) during the past decade. Methods The national database of the German collaborative arthritis centres collects clinical and patient-derived data from unselected outpatients with inflammatory rheumatic diseases. Cross-sectional data from 2000 to 2012 of around 1000 patients with AS per year were compared with regard to clinical presentation and quality of life indicators. Results Non-steroidal anti-inflammatory drugs (NSAIDs) have been the predominant treatment choice in AS over the years with a prescription rate of 67% of patients in 2012. Currently, almost half of the patients with AS in German rheumatology centres are treated with tumour necrosis factor inhibitors (TNFi). Often, both treatments are used in combination (33%), followed by combinations of NSAIDs and synthetic disease modifying antirheumatic drugs (sDMARDs) with 23% or TNFi alone (21%). In 2012, 10% of patients each received NSAID or sDMARD monotherapy. Methotrexate, sulfasalazine, glucocorticoids and analgaesics alone or in combination with other treatments were given to 10% of patients, respectively. Over the years, we have seen remarkable improvements in disease control and patient reported outcomes. These developments are consistent with enhanced functional status, increasing employment rates and decreasing sick leave, hospitalisation and work disability. Conclusions In the German rheumatology secondary/tertiary care setting, routine care of patients with AS has changed tremendously during the past decade. Increasingly, more efficacious treatment options are reflected in improved clinical outcomes, quality of life and participation in the labour force.
    05/2015; 1(1):e000033-e000033. DOI:10.1136/rmdopen-2014-000033
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    ABSTRACT: To compare the 24-month course of health-related quality of life (HRQoL) in patients with long-standing RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) DMARD in daily rheumatological care. Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients' HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores. All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%. Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.
    Rheumatology (Oxford, England) 05/2015; 54(10). DOI:10.1093/rheumatology/kev194 · 4.48 Impact Factor
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    ABSTRACT: Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 04/2015; DOI:10.1136/annrheumdis-annrheumdis-2014-206747 · 10.38 Impact Factor
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    ABSTRACT: Patient reported outcomes (PROs) are relevant in rheumatology. Variable accessibility and validity of commonly used PROs are obstacles to homogeneity in evidence synthesis. The objective of this project was to provide a comprehensive library of "validated PROs". A launch meeting with rheumatologists, PROs methodological experts, and patients, was held to define the library's aims and scope, and basic requirements. To feed the library we performed systematic reviews on selected diseases and domains. Relevant information on PROs was collected using standardised data collection forms based on the COSMIN checklist. The EULAR Outcomes Measures Library (OML), whose aims are to provide and to advise on PROs on a user-friendly manner albeit based on scientific grounds, has been launched and made accessible to all. PROs currently included cover any domain and, are generic or specifically target to the following diseases: rheumatoid arthritis, osteoarthritis, spondyloarthritis, low back pain, systemic lupus erythematosus, gout, osteoporosis, juvenile idiopathic arthritis, and fibromyalgia. Up to 236 instruments (106 generic and 130 specific) have been identified, evaluated, and included. The systematic review for SLE, which yielded 10 specific instruments, is presented here as an example. The OML website includes, for each PRO, information on the construct being measured and the extent of validation, recommendations for use, and available versions; it also contains a glossary on common validation terms. The OML is an in progress library led by rheumatologists, related professionals and patients, that will help to better understand and apply PROs in rheumatic and musculoskeletal diseases.
    Clinical and experimental rheumatology 03/2015; · 2.72 Impact Factor
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    A Zink · J Sieper ·

    Zeitschrift für Rheumatologie 03/2015; 74(2):104-5. DOI:10.1007/s00393-014-1448-2 · 0.61 Impact Factor
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    ABSTRACT: Objectives To evaluate the factors that influence patients with early inflammatory arthritis to consider a disability pension. Methods A total of 528 patients aged 63 or younger from an early arthritis cohort with a mean symptom duration of 3 months at inclusion were asked at 12 and 24 months whether they were considering applying for, had applied for or were receiving a disability pension because of arthritis. Possible predictors were analysed with univariate and multivariate logistic regression. Results 69 patients (13%) were considering, had applied for or were receiving a disability pension. Univariate predictors were older age, disease activity, several patient-reported outcomes and depression. In a multivariate analysis, age, days on sick leave, impairment of physical function and depression were predictive for considering a disability pension (OR for severe vs no depression: 3.85, 95% CI 1.43 to 10.4). Conclusions In patients with early arthritis, depression appears to be a stronger predictor of the risk to consider applying for work disability pension than the features of disease activity. Patients at risk could be identified with one single depression statement. This finding should prompt physicians to react early to signs and symptoms of depression to help patients to maintain their ability to work.
    02/2015; 1(1):e000020-e000020. DOI:10.1136/rmdopen-2014-000020
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    ABSTRACT: To evaluate initial glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA). Six hundred sixty-nine patients with early RA were followed for 2 years in the multicenter "Course And Prognosis of Early Arthritis" cohort. Treatment was applied according to routine care. Assessments included disease activity (DAS28), disability Hannover Functional Status Questionnaire (FFbH), and treatment details. Mixed models, ANCOVA, and logistic regression models were used for statistical analysis. In total, 518 patients (77 %) received oral GCs at baseline; 20 % received a low dose (<7.5 mg prednisolone/day), 22 % received a moderate (7.5-19 mg), and 35 % received a high dose (≥20 mg). In a multivariate logistic regression analysis, higher DAS28 values (OR 1.3) were associated with the use of higher GC doses at baseline (p < 0.001). After adjusting for age, sex, and baseline DAS28 and DMARDs, the patients who started with high-dose GCs had a greater improvement in DAS28 (month 3) and FFbH (month 6, p < 0.001 each). At 2 years, the mean DAS28 remission rates and FFbH values were similar. In all GC groups, the mean dose was tapered to 4 mg/day within 6 months. The reported comorbidities were not increased in patients with high-dose GC therapy. Starting treatment with high-dose GCs led to a better clinical response within 3 to 6 months compared to starting patients on lower dosages. Irrespective of the starting approach, rheumatologists tapered GCs down to a low dose within 6 months. With this strategy, clinical outcomes at 2 years did not differ relevantly.
    Rheumatology International 02/2015; 35(8). DOI:10.1007/s00296-015-3229-x · 1.52 Impact Factor
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    ABSTRACT: To evaluate trends in the referral, treatment and outcome of patients with systemic lupus erythematosus (SLE) in Germany over two decades. From 1993 to 2012, ∼1200 patients with SLE were recorded annually in the national database of the German Collaborative Arthritis Centres. Treatment patterns, healthcare use and outcomes, such as disease activity, function and work participation, were evaluated over time. Furthermore, two distinct cohorts of patients (enrolment 1994-1998, n=467; and 2004-2008, n=376) observed over 5 years were assessed for changes in outcomes. The mean disease duration at the first visit to a rheumatologist decreased from 2.6 (1994) to 1.5 (2012) years. Glucocorticoids (69%), antimalarials (56%), azathioprine (22%), non-steroidal anti-inflammatory drugs (23%) and mycophenolate mofetil (15%) were the most frequently used treatments in 2012. A significant increase was observed in the use of antimalarials and mycophenolate mofetil. The use of glucocorticoids at >7.5 mg/day decreased from 27% (1994) to 10% (2012). The average length of sick leave taken due to SLE declined from 9 weeks (1997) to 6 weeks (2012). When comparing the two longitudinal cohorts, in the cohort from the 2000s, the intraindividual decline of disease activity was significantly stronger (p<0.001), and fewer patients retired early (36% vs 46%). The disease activity and resource use declined considerably over the observation period, and more patients remained in the labour force. Earlier treatment onset, faster modification of the treatment regimen and more intensive use of anti-inflammatory therapy may account for the improved outcomes in patients with SLE across the years.
    12/2014; 1(1):e000059. DOI:10.1136/lupus-2014-000059

  • American Congress of Rheumatology, Boston; 11/2014
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    ABSTRACT: Objective To compare the approved treatment of rheumatoid arthritis using rituximab + methotrexate (RTX + MTX) versus the off-label treatment variants of RTX in monotherapy or RTX in combination with leflunomide (RTX + LEF). Methods We included RTX-naive patients enrolled in the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) between 2007 and 2012 (n = 907) who started treatment with RTX. Three treatment regimens (RTX + MTX, RTX + LEF, and RTX monotherapy) were analyzed regarding therapy discontinuation, dropout, RTX retreatment, and concomitant glucocorticoid therapy. Effectiveness was evaluated with linear mixed models. Results Baseline patient characteristics were similar across treatment regimens, except for poorer functional status and more comorbidities in RTX monotherapy. Average doses of glucocorticoids were lower in RTX + LEF compared to the 2 other groups. The frequency and timing of RTX retreatment (P > 0.62) as well as improvement in the Disease Activity Score in 28 joints (DAS28) over time (P > 0.15) were similar in all treatment regimens. Within the first 12 months of treatment, the DAS28 decreased by 1.5 units, and between months 12 and 36, by a further 0.4 unit equally in all groups. Nevertheless, therapy discontinuation and dropout were significantly increased on RTX monotherapy (hazard ratio [HR] 1.7 [95% confidence interval (95% CI) 1.2–2.3]), and additionally when patients were rheumatoid factor negative (HR 1.5 [95% CI 1.0–2.1]). Conclusion In patients who continue therapy, RTX + LEF, RTX monotherapy, and RTX + MTX seem to be equally effective. However, given the lower adherence rates on monotherapy, this treatment option is not sufficient for all patients. Since many patients are intolerant to MTX, more licensed RTX treatment options are needed.
    11/2014; 66(11). DOI:10.1002/acr.22327
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    ABSTRACT: Objective: To assess reliability and validity of periodontal diagnosis based on routine dental radiographs in an epidemiological study of early rheumatoid arthritis (RA). Method: From a national cohort of 1316 RA patients, 756 completed a follow-up questionnaire about their RA status and oral health. Their general dental practitioners (GDP) were contacted and 354 returned the questionnaires. Routine dental X-rays were available for 254 patients. Three assessors rated the severity of periodontitis (none, mild, moderate, severe) and their level of confidence in the diagnosis (uncertain, pretty certain, certain). Following independent assessments, a consensus was reached by discussion. Cohen’s kappa was calculated for Interrater-agreement and for assessment of validity. Sensitivity and specificity analysis was also calculated for the validity of the consensus based on Xrays compared with the clinical diagnosis provided by GDPs as gold standard. Result: Inter-rater agreement between assessors was fair (K=0.3837). When comparing the consensus of the assessments based on Xrays with the clinical diagnosis, the percent agreement is 76.5% and kappa is very similar with the consensus diagnostics (K=0.389). The level of agreement can increase from fair to moderate when taking into consideration only the assessments with high level of certainty: 78.2% (expected 58.4%, K=0.475). Compared to GDP’s diagnosis, sensitivity was 61.4%, specificity 84.2%; positive predictive value 81.3% and negative predictive value 66.2% . Conclusion: Assessment of periodontitis from routine radiographs sent by GDPs has fair to moderate reliability and validity.
    2014 IADR/PER Congress; 09/2014

Publication Stats

7k Citations
1,012.30 Total Impact Points


  • 2007-2015
    • Charité Universitätsmedizin Berlin
      • Medical Department, Division of Rheumatology and Clinical Immunology
      Berlín, Berlin, Germany
  • 2000-2015
    • German Rheumatism Research Centre
      Berlín, Berlin, Germany
  • 2014
    • University of Birmingham
      • School of Dentistry
      Birmingham, England, United Kingdom
  • 2011
    • University of Applied Sciences Fulda
      Fulda, Hesse, Germany
  • 2005-2008
    • Martin Luther University of Halle-Wittenberg
      • Institut für Rehabilitationsmedizin
      Halle, Saxony-Anhalt, Germany
  • 2006
    • Heinrich-Heine-Universität Düsseldorf
      • Klinik für Endokrinologie, Diabetologie und Rheumatologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1996-2006
    • Deutsches Herzzentrum Berlin
      Berlín, Berlin, Germany