Marjonne C W Creemers

Jeroen Bosch Ziekenhuis, Hertogenbosch, North Brabant, Netherlands

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Publications (37)

  • [Show abstract] [Hide abstract] ABSTRACT: For patients with chronic pain conditions such as rheumatoid arthritis (RA), who experience elevated levels of distress, tailored guided internet-based cognitive behavioral treatment may be effective in improving psychological and physical functioning, and reducing impact the impact of RA on daily life. A multicenter randomized controlled trial was conducted for RA patients with elevated levels of distress asassessed by a disease-specific measure. The control group (n=71) received standard care and the intervention group (n= 62) additionally received an internet-based tailored cognitive-behavioral intervention. Main analyses were performed using a linear mixed model estimating differences between the intervention and control group in scores of psychological functioning, physical functioning, and impact of RA on daily life at pre- and post-assessment, and at 3, 6, 9, and 12 months. Patients who received the internet-based intervention reported a larger improvement in psychological functioning compared to the control group, indicating less depressed mood (p<.001, d=0.54), negative mood (p=.01, d=0.38), and anxiety (p<.001, d=0.48) during the course of the one-year follow-up period. Regarding physical functioning, a trend was found for the intervention group reporting less fatigue than the control group (p=.06, d=0.24), whereas no effect was found on pain. No effects were found for the impact of RA on daily life, except for the intervention group experiencing fewer role limitations due to emotional problems (p<.001, d=0.53). Offering guided internet-based cognitive-behavioral therapy is a promising development to aid patients with psychological distress particularly in improving psychological functioning Further research on adherence and specific intervention ingredients is warranted.
    Article · Jan 2017 · Pain
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    [Show abstract] [Hide abstract] ABSTRACT: Importance Eosinophilic fasciitis (EF) is a connective tissue disorder in which conventional treatment leads to disappointing results in a proportion of patients. Therefore, we investigated high-dose intravenous (IV) pulse methotrexate (MTX) as a treatment for EF. Objective To examine safety and effects of monthly high-dose IV pulse MTX in EF. Design, Setting, and Participants For this prospective single-arm study, we recruited 12 patients diagnosed with biopsy specimen–proven EF between 2006 and 2009 from the Department of Dermatology and Rheumatology at the Radboud University Medical Centre. Interventions Intravenous MTX (4 mg/kg) monthly for 5 months with folinic acid rescue 24 hours after MTX administration. Main Outcomes and Measures The primary outcome was improvement of the modified skin score at month 5 vs baseline. Secondary outcomes were durometry, range of motion, visual analog scale scores for disease activity, and 36-Item Short Form Survey health questionnaires. Results Overall, 12 patients (11 women between 37-69 years old) received a median (range) monthly dose of 288 (230-336) mg MTX. Median (range) modified skin score improved from 17.5 (8.0-24.0) at baseline to 8.5 (1.0-20.0) at month 5 (P = .001). Secondary outcome measures improved significantly, except for durometer scores and range of motion of the elbows. Adverse events included gastrointestinal symptoms (n = 9), mild stomatitis (n = 5), and alopecia (n = 4). Conclusions and Relevance High-dose IV pulse MTX is a safe and effective treatment option in EF. Trial Registration clinicaltrials.gov Identifier: NCT00441961
    Full-text available · Article · Aug 2016 · JAMA Dermatology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Eosinophilic Fasciitis (EF) is a rare scleroderma-like connective tissue disorder. No treatment has shown to be effective in randomized trials. The treatment most often reported is combination of moderate to high-dose glucocorticoids (1-1,5mg/kg/day) with weekly methotrexate (MTX), up to 25mg, but often with disappointing results.(1, 2) Objectives: To examine the effect and safety of monthly intravenous (IV) high dose MTX in patients with eosinophilic fasciitis in an open prospective study. Methods: Patients with biopsy proven EF and progression of skin involvement, who were either treatment naïve or not responsive to glucocorticoids and MTX were included in this open prospective study. Treatment consisted of IV pulse MTX 4 mg/kg/month for 6 doses in 5 consecutive months. Twenty-four hours after the administration of MTX, 5mg folinic acid was orally taken every six hours, to a maximum of 25 mg/day. Patients were evaluated monthly, prior to every infusion. Primary outcome measure was the absolute improvement at month 5 compared to baseline of the modified skin score (mSS), according to Zachariae.(3) Secondary outcome measures were durometer scores, Range of Motion (RoM) and Visual Analogue Scale (VAS) scores for disease activity by physician and patient and Short-Form-36. Results: Between 2006 and 2009, 12 patients were included and the median monthly MTX dose was 288mg (range 252-336). The median mSS improved from 17.5 [range 8.0-24.0] at baseline to 8.5 [range 1.0-20.0] at 5 months (p=0.001) (Fig 1). Compared to baseline, secondary outcome measures improved significantly, except for durometer scores and the range of motion of the elbows. There was no significant difference in skin improvement between the treatment naïve and non-naïve patients (p=0.968). After the last dose of IV MTX, EF flared in six patients after a median of 2 months (range 2-5). A second cycle with IV MTX (3 pulses) was administered to these 6 patients, with a favourable response in all patients. One patient was withdrawn due to increased liver enzymes (2 – times upper limit of normal) after 5 administrations, which normalized after MTX withdrawal. Gastro-intestinal symptoms were present in the majority of the patients (n=9), but manageable with anti-emetics. Conclusion: High dose IV MTX could be an effective and safe treatment option in patients with EF.
    Full-text available · Conference Paper · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Background Eosinophilic Fasciitis is a rare scleroderma-like connective tissue disorder. No treatment has shown to be effective in randomized trials. The treatment most often reported is combination of moderate to high-dose glucocorticoids (1–1,5mg/kg/day) with weekly methotrexate (MTX), up to 25mg, but often with disappointing results.1,2 Objectives To examine the effect and safety of monthly intravenous (IV) high dose MTX in patients wtih eosinophilic fasciits. Methods Patients with biopsy proven eosinophilic fasciits and progression of skin involvement, who were either treatment naïve or not responsive to glucocorticoids and MTX were included in this open prospective study. Treatment consisted of IV pulse MTX 4 mg/kg/month for 6 doses in 5 consecutive months. Twenty-four hours after the administration of MTX, 5mg folinic acid was orally taken every six hours, to a maximum of 25 mg/day. Patients were evaluated monthly, prior to every infusion. Primary outcome measure was the absolute improvement at month 5 compared to baseline of the modified skin score (mSS), according to Zachariae.³ Secondary outcome measures were durometer scores, Range of Motion (RoM) and Visual Analogue Scale (VAS) scores for disease activity by physician and patient and Short-Form-36. Results Between 2006 and 2009, 12 patients were included and the median monthly MTX dose was 288mg (range 252–336). The median mSS improved from 17.5 [range 8.0–24.0] at baseline to 8.5 [range 1.0–20.0] at 5 months (p=0.001) (Fig 1). Compared to baseline, secondary outcome measures improved significantly, except for durometer scores and the range of motion of the elbows. There was no significant difference in skin improvement between the treatment naïve and non-naïve patients (p=0.968). After the last dose of IV MTX, EF flared in six patients after a median of 2 months (range 2–5). A second cycle with IV MTX (3 pulses) was administered to these 6 patients, with a favourable response in all patients. One patient was withdrawn due to increased liver enzymes (2 – times upper limit of normal) after 5 administrations, which normalized after MTX withdrawal. Gastro-intestinal symptoms were present in the majority of the patients (n=9), but manageable with anti-emetics. View larger version: • In a new window • Download as PowerPoint Slide Conclusions High dose IV MTX could be an effective and safe treatment option in patients with eosinophilic fasciitis. • Lebeaux D, Frances C, Barete S, et al. Eosinophilic fasciitis (Shulman disease): new insights into the therapeutic management from a series of 34 patients. Rheumatology. 2012; 51: 557–61. • Wright NA, Mazori DR, Patel M, et al. Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers. JAMA dermatology. 2016; 152: 97–9. • Zachariae H, Bjerring P, Halkier-Sorensen L, et al. Skin scoring in systemic sclerosis: a modification–relations to subtypes and the aminoterminal propeptide of type III procollagen (PIIINP). Acta dermato-venereologica. 1994;74: 444–6. Disclosure of Interest None declared
    Article · Jun 2016 · Annals of the Rheumatic Diseases
  • Article · Nov 2015 · Psychotherapy and Psychosomatics
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    T Schoffelen · L.M. Kampschreur · S.E. van Roeden · [...] · M C W Creemers
    Full-text available · Article · May 2014 · Annals of the rheumatic diseases
  • T. Schoffelen · L. M. Kampschreur · S. E. van Roeden · [...] · M. C. Creemers
    [Show abstract] [Hide abstract] ABSTRACT: Background The Netherlands faced a large Q fever outbreak from 2007-2010, during which many individuals have been infected with Coxiella burnetii, the intracellular bacterium causing Q fever. Initial infection is often asymptomatic. Chronic Q fever, which develops in a minority of infected individuals (1-5%), presents months to years after primary infection, mostly as endocarditis or vascular infection. Immunosuppression, although not clearly defined, is a stated risk factor for chronic Q fever. Anti-TNF therapy is associated with increased risk of intracellular infections. Objectives To examine whether rheumatoid arthritis (RA) patients on anti-TNF therapy are at increased risk of development of chronic Q fever, compared to TNF-naive RA patients using disease modifying drugs (DMARDs). Methods RA patients, living in Q fever epidemic areas, were identified in rheumatology outpatient clinics in participating hospitals. We selected a cohort of patients on anti-TNF therapy (infliximab, etanercept, adalimumab) for at least three months during the epidemic and a cohort TNF-naive patients who were using DMARDs during the same period. Participants were screened for anti-C. burnetii antibodies, measuring IgG against C. burnetii phase I and II in serum. Patients with phase I and/or II IgG titres ≥1:32 were defined as seropositive, indicating previous exposure to C. burnetii. All seropositive individuals were referred for follow-up to the department of internal medicine. Chronic Q fever was diagnosed according to the Dutch guideline on chronic Q fever diagnostics,1 by a team of medical specialists. Results From December 2011 to July 2012, 361 patients on anti-TNF therapy and 398 TNF-naive patients participated. The anti-TNF treated patients more frequently used systemic prednisone (at least three months during the epidemic) (P < 0.001). Of patients on anti-TNF therapy, 60/361 (16.6%) were seropositive, compared to 56/398 (14.1%) of TNF-naive patients (P=0.35). Overall, 10/116 (8.6%) seropositive patients were diagnosed with chronic Q fever, of which 7/60 (11.7%) patients on anti-TNF therapy compared to 3/56 (5.4%) TNF-naive patients (P=0.33). Univariate analysis in seropositive patients identified higher age, the use of systemic prednisone, valvulopathy/prosthetic valve and aneurysm/vascular prosthesis as significant risk factors for chronic Q fever. Conclusions We did not find a significantly higher prevalence of chronic Q fever in patients on anti-TNF therapy compared to TNF-naive patients in this population. Nevertheless, the prevalence of chronic Q fever in seropositive RA patients, either on anti-TNF therapy or DMARD therapy, was substantially higher (8.6%) than reported in non-selected infected individuals (1-5%), suggesting that RA and anti-rheumatic treatment are a risk factor for development of chronic Q fever. Specifically, the use of systemic prednisone was identified as a risk factor in this population. References Acknowledgements Investigators initiated study funded by Pfizer. This work was also supported by The Netherlands Organisation for Health Research and Development [grant number 205520002 to T.Schoffelen] Disclosure of Interest None Declared
    Article · Jun 2013 · Annals of the Rheumatic Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Infliximab is an effective treatment for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis and national and international guidelines have been developed for each indication. WHAT THIS STUDY ADDS This study is the first study which compared current international, national and local guidelines from the medical specialties involved in the treatment with infliximab on the following topics: indication, dosage, synergy and monitoring of vital signs. AIMS Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis. Development of national and international guidelines for rheumatology, gastroenterology and dermatology, was mostly based on clinical studies and expert opinion. The aim of this study was to compare available guidelines and local protocols for rheumatology, dermatology and gastroenterology, regarding dosage of infliximab, synergy of infliximab with concomitant medication and monitoring of vital signs during infliximab administration, for achieving optimal care. METHODS Current international, national and local guidelines on the use of infliximab were reviewed and compared, differences and shortcomings were identified, and optimal treatment schedules discussed during a meeting (July 2008) of clinical experts and researchers from three departments of a Dutch university hospital. RESULTS Recommended dosages of infliximab are not equal for different indications. Loss of response to infliximab is a common problem encountered within the three medical specialties, but indications for adjustments in treatment schedules are lacking in all of the guidelines. Monitoring of vital signs (blood pressure, pulse, temperature) during infusion with infliximab is common practice and recommended by some guidelines. Routine measurement of vital signs is not of any value in predicting or recognizing acute infusion reactions, in our experience, and this is confirmed by literature on inflammatory bowel disease. CONCLUSION Different indications encompass different dosing schedules. National and internal guidelines do not provide advice regarding loss of response. Routine measurement of vital signs during infusion is not valuable in detecting acute infusion reactions and should only be performed in case of an acute infusion reaction. These topics need to be studied in future studies and covered in future guidelines.
    Full-text available · Article · Jul 2010 · British Journal of Clinical Pharmacology
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    [Show abstract] [Hide abstract] ABSTRACT: Stressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases. Databases Medline, PsychINFO, Embase, Cinahl and Pubmed were screened for studies (1985 to 2009) investigating physiological stress responses in inflammatory rheumatic diseases. Eighteen articles met the inclusion criteria. Results suggest that immune function may be altered in response to a stressor; such alterations could contribute to the maintenance or exacerbation of inflammatory rheumatic diseases during stressful events in daily life. This review emphasizes the need for more experimental research in rheumatic populations with controlled stress paradigms that include a follow-up with multiple evaluation points, simultaneous assessment of different physiological stress systems, and studying factors contributing to specific physiological responses, such as stress appraisal.
    Full-text available · Article · May 2010 · Arthritis research & therapy
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    Laura T C van Hulst · Marjonne C W Creemers · Jaap Fransen · [...] · Piet L C M van Riel
    [Show abstract] [Hide abstract] ABSTRACT: To determine whether DAS28 measurements by a specialized nurse, before the rheumatologist visit, in combination with the advice to rheumatologists to reach a DAS28 < or = 3.2, had beneficial effects on disease activity and medication prescription in patients with RA and to explore possible predictors for variation in medication changes and reasons for non-adherence to the advice to reach a DAS28 < or = 3.2. In this pilot study, rheumatologists were randomized to 'usual care' (n = 3) or DAS28 measurement by a nurse prior the rheumatologist visit (n = 4). In the usual care group, the DAS28 was measured but not provided to rheumatologists. Mixed model analyses were used for analysing between-group differences and for the prediction model. Rheumatologists in the intervention group were asked to provide reasons in cases of non-adherence to the advice. After 18 months, DAS28 was reduced by - 0.69 and - 0.66 (P = 0.70) in, respectively, the intervention (144 patients) and the usual care (104 patients) groups. In the intervention group, medication was changed by rheumatologists in 35% of the visits with a DAS28 > 3.2; in the usual care group this was 33% (P = 0.99). Baseline DAS28 (OR 1.6; P< or =0.0001) and HAQ (OR 1.3; P = 0.03) were positively related to a medication change. The most frequently mentioned reason not to change medication was patient refusal (26%). DAS28 measurement by a nurse was as effective as usual care; however, this intervention without protocolized treatment adjustments is not sufficient to lead to a considerable reduction in disease activity compared with trials with protocolized treatment adjustments.
    Full-text available · Article · Apr 2010 · Rheumatology (Oxford, England)
  • Article · May 2009 · Gastroenterology
  • Article · Feb 2009 · The Journal of Rheumatology
  • E.B.M. Kroft · M.C.W. Creemers · F.H.J. van den Hoogen · [...] · E.M.G.J. de Jong
    [Show abstract] [Hide abstract] ABSTRACT: Detailed information is lacking on effectiveness of methotrexate (MTX) in sclerotic skin diseases, side-effects, and duration of remission after discontinuation. To determine effectiveness, side-effects and period of remission gained by use of MTX in sclerotic skin diseases. All patients with a sclerotic skin disease who were treated with MTX (group A) or MTX with corticosteroids (CS) (group B) between 1995 and 2007 were evaluated. Detailed information was collected on dosage and duration of MTX treatment, concomitant immunosuppressive medication and CS treatment, effectiveness, side-effects, duration of the remission period, and time until restart. Fifty-eight patients (A, n = 47; B, n = 11) were evaluated. Clinical assessment revealed that 38 patients (81%) treated with MTX and 11 patients (100%) treated with MTX + CS showed improvement of sclerotic skin. After one treatment course 51% of the patients treated with MTX and 73% treated with MTX + CS reached remission status with a median follow-up time of 55 and 58 months. Patients showing relapse still responded to a second and even to a third course of MTX. Patients who showed a relapse had received a lower cumulative dose, due to a shorter period of treatment with MTX in the first course. Serious side-effects were seen in six patients (10%). MTX was an effective treatment for various sclerotic skin diseases with a long period of remission and relatively low toxicity. Patients showing relapse still responded to a second and third course of MTX.
    Article · Feb 2009 · British Journal of Dermatology
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    [Show abstract] [Hide abstract] ABSTRACT: The guanine-thymidine (GT)n repeat in the HMOX1 promoter determines the level of induction of the heme-degrading enzyme heme oxygenase 1 (HO-1), which protects against inflammatory and oxidative stress. In individuals with short (GT)n repeats (where n < 25; SS genotype), higher levels of HO-1 activity are induced more rapidly than in those with long (GT)n repeats (where n > or = 25; LL genotype). Recently, it was demonstrated that HO-1 activity protects against the onset of rheumatoid arthritis (RA). The aim of this study was to determine whether the (GT)n-repeat length within the HMOX1 promoter region is associated with RA disease severity and radiographic joint damage. A cohort of 325 well-characterized RA patients and 273 controls was investigated by DNA fragment-length analysis for the association of (GT)n repeats in the HMOX1 promoter region with RA disease susceptibility and severity. Although no significant differences in genotype or allele frequency were found between controls and RA patients, the odds ratios corresponded well to those in the previously described cohort. Among patients, those carrying the SS genotype had a more favorable radiographic outcome over 9 years than those carrying the LL genotype. This was unexpected since no differences in disease activity were found between the genotypes or alleles. Patients with the SS genotype have a better long-term radiographic outcome despite poor prognostic markers at baseline and despite disease activity at followup similar to that of patients with the LL genotype. This suggests that the HMOX1/HO-1 system is involved in the uncoupling of disease activity and joint damage and may provide a novel target for the treatment of RA.
    Full-text available · Article · Nov 2008 · Arthritis & Rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: To assess the effect of a functional polymorphism (676T>G, M196R) in the tumour necrosis factor receptor super family 1b (TNFSF1b) gene on disease activity, radiological joint damage and response to infliximab and adalimumab treatment in patients with rheumatoid arthritis (RA). Two cohorts of patients with RA were genotyped for the 676T>G polymorphism (rs1061622) in exon 6 of the TNFSF1b gene by restriction fragment length polymorphism analysis. One cohort (n = 234) included patients from the Dutch Rheumatoid Arthritis Monitoring register with detailed information on their response to anti-TNF therapy (infliximab and adalimumab), the other cohort comprised patients from a long-term observational early inception cohort at our centre (n = 248). The 676T>G polymorphism was not associated with anti-TNF response after 3 or 6 months of treatment. Linear regression analysis showed no significant difference in the progression of radiological joint damage during the first 3 and 6 years of disease between the three genotype groups (TT, TG and GG). Additionally, no difference in mean disease activity between genotypes was seen after 3 and 6 years of disease. Despite its demonstrated functionality, the 676T>G polymorphism in the TNFSF1b gene does not have a major role in either the response to anti-TNF therapy or in the disease severity or radiological progression in RA.
    Article · Sep 2008 · Annals of the rheumatic diseases
  • Antoine W T van Lieshout · Marjonne C W Creemers · Timothy R D J Radstake · [...] · Piet L C M van Riel
    Article · Jun 2008 · The Journal of Rheumatology
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    Annelies E. van Ede · Alfons A. den Broeder · Michiel Wagenaar · [...] · Marjonne C W Creemers
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Although nodulosis is a common extraarticular manifestation of rheumatoid arthritis, accelerated pulmonary nodulosis is a rare event. The etiology of rheumatoid nodules is still unknown. Nodulosis is not necessarily associated with active joint inflammation, suggesting different pathogenic mechanisms for nodule formation and synovial tissue inflammation. We describe a patient with extensive pulmonary nodulosis, probably related to etanercept treatment. Our case emphasizes the need for careful monitoring for adverse events during treatment with biologicals, especially since the differential diagnosis often includes a broad spectrum of diseases.
    Full-text available · Article · Aug 2007 · The Journal of Rheumatology
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    Alfons A den Broeder · Marjonne C W Creemers · Jaap Fransen · [...] · Frank H J van den Hoogen
    [Show abstract] [Hide abstract] ABSTRACT: To identify risk factors for surgical site infection (SSI) in patients with rheumatoid arthritis (RA) with special attention for anti-tumor necrosis factor (anti-TNF) treatment. All patients with RA who had undergone elective orthopedic surgery since introduction of anti-TNF were included in a retrospective parallel-cohort study with a one-year followup. Primary endpoint was a SSI according to the 1992 Centers for Disease Control and Prevention criteria and/or antibiotic use. Cohort 1 did not use anti-TNF, cohort 2 used anti-TNF but had either stopped (2A) or continued anti-TNF preoperatively (2B), the cutoff point being set at 4 times the half-life time of the drug. Infection rates were compared between cohorts, and logistic regression analysis was performed to examine risk factors. In total, 1219 (768 patients) procedures were included, and crude infection risks were 4.0% (41/1023), 5.8% (6/104), and 8.7% (8/92) in cohorts 1, 2A, and 2B, respectively. Elbow surgery (OR 4.1, 95% CI 1.6-10.1), foot/ankle surgery (OR 3.2, 95% CI 1.6-6.5), and prior skin or wound infection (OR 13.8, 95% CI 5.2-36.7) were associated with increased risk of SSI, whereas duration of surgery (OR 0.42, 95% CI 0.23-0.78) and sulfasalazine use (OR 0.21, 95% CI 0.05-0.89) were associated with decreased risk. Perioperative use of anti-TNF was not significantly associated with an increase in SSI rates (OR 1.5, 95% CI 0.43-5.2). The most important risk factor for SSI is history of SSI or skin infection. Although our study was not powered to detect small differences in infection rates, perioperative continuation of anti-TNF does not seem to be an important risk factor for SSI.
    Full-text available · Article · May 2007 · The Journal of Rheumatology
  • J W G Jacobs · M C W Creemers · M A van Agtmael · [...] · J W J Bijlsma
    [Show abstract] [Hide abstract] ABSTRACT: Anti-tumour necrosis factor (TNF) therapy is associated with an increased risk of infection. There are sparse data and no evidence-based guidelines on how to deal with this problem in daily practice. However, recommendations can be made based on theoretical considerations and by extrapolating from recommendations for other types ofimmunodeficiency. Before starting anti-TNF therapy, screening for tuberculosis and other possible infections is indicated. During therapy, alertness is required to the increased risk of infection, infections with a more serious clinical course or unusual manifestations and opportunistic infections. Flu vaccination during anti-TNF therapy is indicated. Travel vaccinations with live microbial inocula should not be given.
    Article · Mar 2007 · Nederlands tijdschrift voor geneeskunde
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    M Flendrie · M C W Creemers · P L C M van Riel
    [Show abstract] [Hide abstract] ABSTRACT: To observe the course of the disease activity in rheumatoid arthritis (RA) patients treated with the standard infliximab dosing regimen and to adjust treatment guided by the pattern of disease activity. All RA patients starting infliximab treatment were included and observed for at least 37 weeks. At infusion 4 (week 14), European League Against Rheumatism response was assessed. In moderate responders the dose was unchanged and the disease activity was carefully observed. In case of stable disease activity, the dose was increased at infusion 5 (week 22). In case of a temporary response the interval was reduced. Paired t-testing was applied to the disease activity score with 28-joint counts (DAS28) at week 22 and study endpoint. A total of 76 patients were included. Response after 14 weeks: good 22 (29%) patients, moderate 26 (34%) patients, and non-response in 21 patients. Seven patients (9%) dropped out before week 14 due to adverse events (5) or patients' initiative (2). In patients with moderate response, the following disease course between infusion 4 and 5 was observed: improvement to good response 6, temporary response 6, stable disease activity 6, drop out 8. In moderate responders, interval reduction and dose increase resulted in a decrease in mean DAS28 from 5.1 to 3.6 [P = 0.005, mean interval 5.6 weeks, mean infliximab dose 4.8 mg/kg/8 week (endpoint)] and from 4.1 to 3.6 [P = 0.04, mean infliximab dose 7.3 mg/kg/8 week (endpoint)], respectively. Three different patterns of disease activity were observed in moderate responders after 14 weeks of infliximab treatment, i.e. further improvement, no change in disease activity or a temporary response. Both interval reduction and dose increase significantly reduced disease activity, however, with different mean infliximab dosages. In good responders the response was often sustained over follow-up, whereas non-responders showed modest or no improvement despite dose adjustments.
    Full-text available · Article · Feb 2007 · Rheumatology

Publication Stats

1k Citations

Institutions

  • 2013
    • Jeroen Bosch Ziekenhuis
      Hertogenbosch, North Brabant, Netherlands
  • 2004
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 2003
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands