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A A den Broeder

Publications and source records attributed to A A den Broeder.

8 recordsLinked to original sources
PubMed2005

Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthritis patients in clinical practice.

BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled studies. However, long term post-marketing efficacy data are lacking. OBJECTIVE: To evaluate the efficacy, safety, and drug survival of anakinra in clinical practice. METHODS: All patients with rheumatoid arthritis who started anakinra in six hospitals between May 2002 and February 2004 were included in a two year prospective, in part retrospective, cohort study. Efficacy was assessed using the 28 joint disease activity score (DAS28) and the EULAR response criteria. Safety was evaluated using the common toxicity criteria. Drug survival and prognostic factors were analysed using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: After three months, 55% of the patients (n = 146) showed a response (43% moderate, 12% good). A subset of patients continuing anakinra after 18 months had a sustained clinical response compared with patients who switched to other disease modifying antirheumatic drug treatment (DAS28 improvement, 2.46 v 1.79). Drug survival was 78%, 54%, and 14% after three, six, and 24 months, respectively. The reason for discontinuation was lack of efficacy in 78% and adverse events in 22%. Except for higher drug survival in women (odds ratio = 0.51, 95% confidence interval, 0.27 to 0.97), no prognostic factors were found. Adverse events were reported 206 times in 111 patients, the most common being injection site reactions (36%). Serious adverse events occurred in 12% of the patients, with one classified as related. CONCLUSIONS: The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies. However, the drug survival of anakinra after two years is low, mostly because of lack of efficacy.

Aged↗
PubMed2003

Disseminated Mycobacterium gordonae infection in a renal transplant recipient.

The use of more intensive immunosuppressive regimens and the increasing number of patients that are exposed to immunosuppressive strategies in transplantation medicine have changed the spectrum of infections that is encountered by the clinician. We describe a 62-year-old female renal transplant recipient receiving immunosuppressive therapy who developed complaints of weight loss, diarrhoea, cough, and fever. Increased C-reactive protein and pancytopenia were found. The presence of Mycobacterium gordonae, a non-tuberculous mycobacterium, was eventually demonstrated in bronchoalveolar lavage fluid, bone marrow, spleen, and liver. Determination of the pathogen was accelerated using a Line Probe Assay, a reverse hybridisation technique using an RNA fragment specific for different mycobacterium species. Treatment was initiated using a combination of clarithromycin, ethambutol, and rifampicin. The initial response to treatment was good, but splenectomy and change of immunosuppressive and antimycobacterial therapy were necessary for long-term control of the infection. Problems in the diagnosis and treatment of this uncommon pathogen are discussed.

Bone Marrow↗
PubMed2003

Survival during treatment with tumour necrosis factor blocking agents in rheumatoid arthritis.

Tumour necrosis factor (TNF) blocking agents are an important advance in the clinical treatment of rheumatoid arthritis (RA). They were introduced into clinical practice while limited safety information was available. This means that intensive monitoring is needed early in the life cycle of these new drugs. Setting up large cohort studies to monitor efficacy, safety, and tolerability in long term use of these so-called biological agents will provide information about the consequences of using TNF blocking agents in chronic rheumatic disease like RA. Currently, a Dutch multicentre registry on biological agents in RA is being set up. This study aimed at investigating the efficacy and toxicity of TNF blocking agents in patients with RA at one participating academic centre by a drug survival analysis. Since 1997 230 patients with RA at the centre have been treated with TNF blocking agents for the first time (94 with adalimumab, 120 with infliximab, and 16 with etanercept). No differences in drug survival between the three TNF blocking agents were found despite the diversity in selection and patient numbers. Adverse events which occurred, leading to discontinuation, were similar to those from previous reports.

Adalimumab↗
PubMed2003

Nephrotic syndrome as a complication of anti-TNFalpha in a patient with rheumatoid arthritis.

We describe a patient with rheumatoid arthritis (RA) who developed a nephrotic syndrome during treatment with a fully human recombinant monoclonal antibody against TNFalpha (adalimumab, Humira, Abbott). The proteinuria disappeared spontaneously after cessation of anti-TNFalpha treatment and relapsed after rechallenge, pointing to anti-TNFalpha as the culprit. Although renal biopsy disclosed a membranous glomerulopathy, the clinical picture was more compatible with minimal lesion glomerulopathy. The pathogenesis of this side effect is not clear; several mechanisms could in theory lead to these abnormalities.

Adalimumab↗
PubMed2002

Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation.

OBJECTIVES: To investigate the effect of prolonged neutralisation of tumour necrosis factor alpha (TNFalpha) on the radiological course in rheumatoid arthritis (RA). To assess whether the radiological course can be predicted by clinical variables or biological markers of cartilage and synovium turnover and of endothelial activation. PATIENTS AND METHODS: Forty seven patients with active RA enrolled at our centre in monotherapy trials with adalimumab (D2E7), a fully human anti-TNFalpha monoclonal antibody, were studied for two years. Radiographs of hands and feet obtained at baseline and after one and two years were scored in chronological order by a single, blinded observer using the modified Sharp method. Radiological course was classified as stable or progressive using the smallest detectable difference as cut off point. The relation between radiological course and serum markers of cartilage and synovium turnover (metalloproteinases (MMP-1 and MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein-39 (HC gp-39)), endothelial activation (soluble E-selectin and intercellular adhesion molecule (ICAM-1)), and integrated measures of disease activity were assessed using univariate and multivariate analysis. RESULTS: Radiological evaluation was performed in 36 patients with paired sets of radiographs at baseline and two years. After two years a total of 15/36 (42%) presented no radiological progression. More patients with stable radiological course were still receiving anti-TNFalpha treatment after two years (13/15 (87%) v 11/21 (52%); p=0.03) and had lower baseline COMP and sICAM-1 levels (p=0.01 and 0.04, respectively) than those in the group with progressive disease. In a logistic regression model the combination of sustained TNF neutralisation and baseline COMP and sICAM-1 levels was predictive for radiological outcome (p=0.03). C reactive protein and disease activity score area under the curve were significantly correlated with changes in radiological scores after two years (r=0.40 and 0.37, p<0.05). Long term TNFalpha neutralisation decreased the levels of COMP, sICAM, MMPs, and HC gp-39, but not sE-selectin. CONCLUSION: The results suggest that long term monotherapy with anti-TNFalpha has a positive effect on radiological outcome and modulates cartilage and synovium turnover as measured by biological markers. Baseline serum sICAM-1 levels and COMP levels may be helpful to identify patients with progressive or non-progressive radiological outcome.

Adalimumab↗
PubMed2001

Isolated digital vasculitis in a patient with rheumatoid arthritis: good response to tumour necrosis factor alpha blocking treatment.

Tumour necrosis factor alpha (TNFalpha) blocking agents are among the most promising new treatments for rheumatoid arthritis (RA). However, no data exist about the effect of these agents on extra-articular manifestations of RA. A patient is described with small vessel vasculitis that repeatedly responded well to treatment with the soluble p55 TNFalpha receptor fusion protein Ro 45-2081 (lenercept).

Arthritis, Rheumatoid↗
PubMed2001

Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis.

OBJECTIVES: To study the short term effects of a single dose of D2E7, a fully human anti-tumour necrosis factor (TNFalpha) monoclonal antibody (mAb), on the local and systemic homeostasis of interleukin 1beta (IL1beta) and TNFalpha in patients with rheumatoid arthritis (RA). METHODS: All patients with RA enrolled in a phase I, single dose, placebo controlled study with D2E7 in our centre were studied. Systemic cytokine levels, acute phase reactants, and leucocyte counts were studied at days 0, 1, and 14 after the first administration of anti-TNF mAb (n=39) or placebo (n=11). The cellularity and the expression of IL1 and TNFalpha in synovial tissue were studied in knee biopsy specimens obtained at baseline and at day 14 in 25 consenting patients. RESULTS: A single dose of anti-TNF mAb induced a rapid clinical improvement, a decrease in acute phase reaction, and increased lymphocyte counts in patients with active RA. The protein levels of IL1beta in the circulation were low and remained unchanged, but the systemic levels of IL1beta mRNA (p=0.002) and the concentrations of IL1 receptor antagonist (IL1ra) and IL6 (p=0.0001) had already dropped within 24 hours and this persisted up to day 14. Systemic levels of TNFalpha mRNA were low and remained unchanged, though total TNFalpha (free and bound) in the circulation increased after D2E7, probably reflecting the presence of TNF-antiTNF mAb complexes (p<0.005, at days 1 and 14). Both TNF receptors dropped below baseline levels at day 14 (p<0.005). Despite clinical improvement of arthritis, no consistent immunohistological changes were seen two weeks after anti-TNF administration. Endothelial staining for IL1beta tended to decrease in treated patients (p=0.06) but not in responders. The staining for IL1beta and TNFalpha in sublining layers and vessels was mutually correlated (r(s)=0.47 and 0.58 respectively, p<0.0005) and the microscopic scores for inflammation correlated with sublining TNFalpha and IL1beta scores (r(s)=0.65 and 0.54 respectively, p<0.0001), though none of these showed significant changes during the study. CONCLUSIONS: Blocking TNFalpha in RA results in down regulation of IL1beta mRNA at the systemic level and in reduction of the endogenous antagonists for IL1 and TNF and of other cytokines related to the acute phase response, such as IL6, within days. At the synovial level, anti-TNF treatment does not modulate IL1beta and TNFalpha in the short term. The synovial expression of these cytokines does not reflect clinical response to TNF neutralisation.

Aged↗