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H Mielants

Publications and source records attributed to H Mielants.

At least 37 records · Page 2Linked to original sources
PubMed2003

Anti-saccharomyces cerevisiae IgA antibodies are raised in ankylosing spondylitis and undifferentiated spondyloarthropathy.

OBJECTIVES: To investigate whether anti-Saccharomyces cerevisiae antibodies (ASCA), a marker for Crohn's disease (CD), are present in spondyloarthropathies (SpA) and in the subgroups ankylosing spondylitis (AS), undifferentiated SpA (uSpA), and psoriatic arthritis (PsA), in comparison with healthy and inflammatory controls (patients with rheumatoid arthritis (RA)). METHODS: ASCA IgA and IgG levels were measured with an enzyme linked immunosorbent assay (ELISA) kit (Medipan, Germany) in 26 patients with CD, 108 patients with SpA (43 patients with AS, 20 patients with uSpA, 45 patients with PsA), 56 patients with RA and 45 healthy controls. Gut biopsy samples were available in 18 AS and 10 patients with uSpA, these samples were screened for the presence of inflammation. RESULTS: Both ASCA IgG and IgA levels were raised in CD compared with healthy controls and patients with RA. ASCA IgA, but not IgG levels, were higher in SpA than in both healthy and RA controls. ASCA IgA levels were raised in AS and uSpA, but not in PsA. No significant differences in ASCA IgA levels were noted between patients with SpA with and without histological gut inflammation. CONCLUSION: ASCA IgA levels are significantly higher in SpA, and more specifically in AS, than in healthy controls and patients with RA. This is the first serum marker associated with SpA. No correlation between the presence of subclinical bowel inflammation and ASCA IgA levels was noted. However, it remains to be evaluated whether patients with SpA with ASCA have an increased risk of developing CD.

Adult↗
PubMed2003

Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries.

OBJECTIVE: To assess direct costs associated with ankylosing spondylitis (AS). To determine which variables, including country, predict costs. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study and filled in bimonthly economic questionnaires. Disease related healthcare resource use was measured and direct costs were calculated from a societal perspective (true cost estimates) and from a financial perspective (country-specific tariffs). Predictors of costs were assessed using Cox's regression analysis. RESULTS: 209 patients provided sufficient data for cost analysis. Mean annual societal direct costs for each patient were euro;2640, of which 82% were direct healthcare costs. In univariate analysis costs were higher in the Netherlands than in Belgium, but this difference disappeared after adjusting for baseline differences in patients' characteristics among countries. Longer disease duration, lower education, worse physical function, and higher disease activity were predictors of costs. Mean annual direct costs from a financial perspective were euro;2122, euro;1402, and euro;941 per patient in the Netherlands, France, and Belgium, respectively. For each country, costs from a financial perspective were significantly lower than costs from a societal perspective. CONCLUSION: Direct costs for AS are substantial in three European countries but not significantly different after adjusting for baseline characteristics among countries. Worse physical function and higher disease activity are important determinants of costs, suggesting better disease control might reduce the costs of AS. The difference in costs from a societal and financial perspective emphasises the importance of an economic analysis.

Adolescent↗
PubMed2003

Costs of ankylosing spondylitis in three European countries: the patient's perspective.

OBJECTIVE: To assess a patient's out of pocket costs, income loss, time consumption, and quality of life (QoL) due to ankylosing spondylitis (AS) in three European countries and to assess variables predicting these outcomes. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year study. Health resource use, days absent from work, time lost, and quality of life (EuroQol) were assessed by bimonthly questionnaires. AS related healthcare and non-healthcare expenditure and income loss were calculated taking into account country-specific regulations. Predictors of costs, time consumption, and QoL were analysed by Cox's regression. RESULTS: 209 patients provided data for cost analysis. Average annual healthcare and non-healthcare expenditure was euro;431 per patient and average annual income loss was euro;1371 per patient. Healthcare costs were highest for Belgian and lowest for French patients, while non-healthcare costs were highest for Dutch patients. A patient's total costs were associated with higher age and worse physical function. On average, patients with AS needed 75 minutes additional time a day because of AS. Worse physical function and higher disease activity predicted time consumption. After adjusting for baseline confounders, QoL was worse in Belgian and French than in Dutch patients. Peripheral arthritis, worse physical function, higher disease activity, and loss of income contributed to worse QoL. CONCLUSION: AS is time consuming and associated with substantial out of pocket costs. Belgian patients incur the highest healthcare payments. Poor physical function increases patient's costs and time consumption. Loss of income is associated with lower QoL.

Adolescent↗
PubMed2003

Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?

BACKGROUND: Recent studies with infliximab indicate the therapeutic potential of tumour necrosis factor alpha blockade in spondyloarthropathy (SpA). Because defective host defence is implicated in the pathogenesis of SpA, the potential side effects of this treatment due to impact on the antimicrobial defence are a major concern. OBJECTIVE: To report systematically the adverse events seen in a large cohort of patients with SpA treated with infliximab, with special attention to bacterial infections. PATIENTS AND METHODS: 107 patients with SpA were treated with infliximab for a total of 191.5 patient years. All serious and/or treatment related adverse events were reported. RESULTS: Eight severe infections occurred, including two reactivations of tuberculosis and three retropharyngeal abscesses, and six minor infections with clear bacterial focus. One patient developed a spinocellular carcinoma of the skin. No cases of demyelinating disease or lupus-like syndrome were seen. Two patients had an infusion reaction, which, however, did not relapse during the next infusion. Finally, three patients with ankylosing spondylitis developed palmoplantar pustulosis. All patients recovered completely with adequate treatment, and infliximab treatment had to be stopped in only five patients with severe infections. CONCLUSIONS: Although the global safety of infliximab in SpA is good compared with previous reports in rheumatoid arthritis and Crohn's disease, the occurrence of infections such as tuberculosis and retropharyngeal abscesses highlights the importance of careful screening and follow up. Focal nasopharyngeal infections and infection related symptoms, possibly induced by streptococci, occurred frequently, suggesting an impairment of specific host defence mechanisms in SpA.

Adult↗
PubMed2002

Increase in lymphoid follicles and leukocyte adhesion molecules emphasizes a role for the gut in spondyloarthropathy pathogenesis.

The aim of this study was to investigate the expression of leukocyte adhesion molecules and the number of lymphoid follicles in gut mucosa of patients with spondyloarthropathy (SpA) in comparison with controls, in search for early immune alterations in the development of SpA-related gut inflammation. Histological evaluation and immunohistochemistry were performed on the ileum and colon of 14 SpA patients without macroscopic or microscopic gut inflammation and those of 21 controls. Lymphoid follicles were counted and immunohistochemical staining for leukocyte adhesion molecules, lymphocyte subtypes, macrophages, and plasma cells was scored semi-quantitatively. The number of lymphoid follicles was increased in both the ileum (p < 0.01) and the colon (p < 0.01) of SpA patients. SpA ileum showed an increase in leukocytes expressing CD11c (p < 0.01), whereas CD11a(+) (p < 0.02) and VCAM-1(+) cells (p < 0.05) were increased in SpA colon. Macrophages, characterized by the expression of CD68, were more numerous in colonic mucosa from SpA patients (p < 0.05). The amount of lymphoid follicles and lamina propria mononuclear cells expressing CD11a, CD11c, and VCAM-1 was increased in non-inflamed gut mucosa from SpA patients. These findings might point to increased antigen handling and presentation and augmented maturation of naïve T cells towards memory T cells in the SpA gut, which supports the concept that the gut is involved in the pathogenesis of SpA.

Adult↗
PubMed2002

Repeated infusions of infliximab, a chimeric anti-TNFalpha monoclonal antibody, in patients with active spondyloarthropathy: one year follow up.

BACKGROUND: In a pilot study, the anti-tumour necrosis factor alpha monoclonal antibody, infliximab, induced a rapid and significant improvement in global, peripheral, and axial disease manifestations of patients with active spondyloarthropathy. OBJECTIVE: To determine whether repeated infusions of infliximab would effectively and safely maintain the observed effect. METHODS: Safety and efficacy of a maintenance regimen (5 mg/kg infliximab every 14 weeks) was evaluated using the measurements reported in the pilot study. Of the 21 patients, 19 completed the one year follow up for efficacy; two patients changed to another dosing regimen after week 12 owing to partial lack of efficacy. However, they are still being followed up for safety analysis. RESULTS: After each re-treatment a sustained significant decrease of all disease manifestations was observed. Before re-treatment, symptoms recurred in 3/19 (16%) at week 20, in 13/19 (68%) at week 34, and in 15/19 (79%) at week 48. No withdrawals due to adverse events occurred. Twelve minor infectious episodes were observed. Twelve patients (57%) developed antinuclear antibodies; in four of them (19%) anti-dsDNA antibodies were detected. However, no lupus-like symptoms occurred. CONCLUSION: In this open study of infliximab in patients with active spondyloarthropathy, the significant improvement of all disease manifestations was maintained over a one year follow up period without major adverse events. Although recurrence of symptoms was noted in a rising number of patients before each re-treatment, no loss of efficacy was observed after re-treatment.

Adult↗
PubMed2002

Work status and productivity costs due to ankylosing spondylitis: comparison of three European countries.

OBJECTIVE: To compare work disability, sick leave, and productivity costs due to ankylosing spondylitis (AS) of three European countries. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study. Employment and work disability rates at baseline were adjusted for age and sex. Productivity costs were calculated by both the friction cost method and the human capital approach. The adjusted contributions of country to employment, work disability, and having an episode of sick leave were assessed by logistic regression and the contribution of the country to days of sick leave and costs by Cox proportional hazard analysis. RESULTS: 209 patients completed the two years' follow up with sufficient data for cost analysis. Adjusted employment was 55% in the Netherlands as compared with 72% in both other countries and only in the Netherlands was it lower than expected in the general population. Adjusted work disability was 41%, 23%, and 9% in the Netherlands, France, and Belgium and in all countries was higher than expected in the general population. In those with a paid job, the mean number of days of sick leave per patient per year because of AS was 19 (range 0-130), six (range 0-77), and nine (range 0-60 ) in the Netherlands, France, and Belgium respectively. Applying the friction cost method to those with a paid job resulted in mean costs per patient per year of 1257 euros (range 0-7356), 428 euros (range 0-5979), and 476 euros (range 0-2354) in the Netherlands, France, and Belgium. Applying the human capital approach to the whole group resulted in mean costs per patient per year of 8862 euros (range 0-46 818), 3188 euros (range 0-43 550), and 3609 euros (range 0-34 320) in the three countries, respectively. After adjusting for sociodemographic and disease characteristics, living in the Netherlands, as compared with both other countries, was associated with a higher chance of being work disabled (odds ratio (OR)=3.82; 95% confidence interval (CI) 1.33 to 11.01), but not with the risk of having an episode of sick leave. Similarly, living in the Netherlands contributed independently to the number of days sick leave (OR=0.65; 95% CI 0.43 to 0.97), a higher amount of friction costs (OR=0.63; 95% CI 0.42 to 0.96), and a higher amount of human capital costs (OR=0.46; 95% CI 0.32 to 0.68). CONCLUSION: There are remarkable differences in work status and productivity costs between the three European countries. This has implications for the generalisability of health economic studies.

Adult↗
PubMed2002

Reliability of self assessed joint counts in ankylosing spondylitis.

OBJECTIVE: To determine the reliability of self reported joint counts to assess pain or swelling in ankylosing spondylitis (AS). METHODS: 217 outpatients fulfilling the modified New York criteria for AS were asked to mark painful joints and swollen joints on two mannequins presenting 44 and 40 joints respectively. A doctor or research nurse assessed the same joints for pain and swelling on the same day, after completion by the patient, without information on the results of the patient's assessment. RESULTS: Forty six (21%) patients reported one or more swollen joints (mean number of swollen joints 0.5, range 0-8); the doctor found one or more swollen joints in 54 (25%) of the patients (mean number of swollen joints 0.8, range 0-31). The overall agreement on the number of swollen joints between patients and doctor was moderate (intraclass correlation coefficient (ICC) 0.53). Agreement on individual swollen joints was poor to moderate (kappa 0.1-0.64). 128 (60%) patients reported tender joints (mean number of joints 2.4, range 0-26). The doctors reported one of more tender joints in 50% of the patients (mean number of tender joints 2.2, range 0-34). The overall agreement was also moderate (ICC 0.71). The agreement on individual tender joints was again poor to moderate (kappa 0.19-0.43). There was only high concordance between doctors and patients on the absence of swollen joints (82%). The concordance on the presence of monoarthritis, oligoarthritis, or polyarthritis was low (17-22%). CONCLUSION: Owing to these discrepancies in assessment of individual joints and total number of affected joints, joint counts in AS assessed by doctors cannot be replaced by joint counts reported by the patients. Patients are only able to judge if their joints are not swollen.

Adolescent↗
PubMed2002

Anti-tumour necrosis factor alpha therapy for ankylosing spondylitis: international experience.

The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor alpha (TNFalpha) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFalpha, which have included approximately 300 patients with SpA. Specifically, TNFalpha-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFalpha and other emerging biological agents.

Aged↗
PubMed2001

Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy: histologic findings in eight patients from an open-label pilot study.

OBJECTIVE: To assess the effects of treatment with anti-tumor necrosis factor alpha (anti-TNFalpha) on synovial histology in patients with spondylarthropathy (SpA) in order to confirm the effect on peripheral synovitis and to investigate the immunologic mechanisms involved in anti-TNFalpha therapy. METHODS: Patients with treatment-resistant SpA were treated with infliximab (5 mg/kg) at weeks 0, 2, and 6 in an open-label pilot study. In 8 patients, synovial biopsy tissues obtained at baseline, week 2, and week 12 were used for histologic and immunohistochemical evaluation. RESULTS: In all 8 patients (3 with ankylosing spondylitis, 1 with undifferentiated SpA, and 4 with psoriatic arthritis), there was a clear clinical improvement in the peripheral arthritis after anti-TNFalpha therapy. Histologic analysis of the synovial biopsy tissues indicated that the synovial lining layer thickness tended to decrease, with a significant reduction of CD55+ synoviocytes, at week 12. In the sublining layer, vascularity was reduced at week 12, with a decreased endothelial expression of vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and E-selectin. Although at week 2 and week 12, the number of neutrophils and CD68+ macrophages in the sublining layer was decreased, the overall degree of inflammatory infiltration remained unchanged. This could be related to the lymphocyte infiltration since at week 12, only CD4+ cells (but not CD3+, CD45RO+, and CD8+ cells) tended to decrease, while CD20+ lymphocytes and plasma cells were clearly increased. CONCLUSION: The reduction in lining layer thickness, vascularity, and infiltration with neutrophils and macrophages paralleled the beneficial effect of anti-TNFalpha therapy on peripheral synovitis in 8 patients with different subtypes of SpA. The adhesion molecule expression, T cell infiltration, and, most important, B cell infiltration seemed to contrast with previous observations in RA. Although these preliminary data need to be confirmed in a larger cohort, they suggest distinct immunomodulatory mechanisms of anti-TNFalpha in SpA.

Adjuvants, Immunologic↗
PubMed2001

The proportion of Th1 cells, which prevail in gut mucosa, is decreased in inflammatory bowel syndrome.

T lymphocytes and their cytokines have an important role in the regulation of immune responses in the gut and in the pathogenesis of intestinal inflammation such as in Crohn's disease. The aim of this study was to analyse the Th1/Th2 cytokine profile (IFN-gamma, IL-2, IL-4 and IL-10) in intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) in Crohn's disease (CD) and ulcerative colitis (UC) in relation to healthy controls (C). Colonic and ileal biopsy specimens were obtained from controls (n = 13) and patients with CD (n = 32). Colonic biopsies were obtained from patients with UC (n = 11). Intracytoplasmic IFN-gamma, IL-2, IL-4 and IL-10 were determined by flow cytometry after PMA-ionomycin stimulation in IEL and LPL. In colonic LPL, a significant proportional decrease of IFN-gamma and IL-2 producing CD3+ cells was observed in patients with CD and UC compared to controls. In ileal LPL, a similar tendency was found although differences were not significant. In IEL no differences in cytokine profiles could be observed. Flow cytometric analysis of intracytoplasmic cytokines at single cell level showed a proportional decrease of IFN-gamma and IL-2 producing T cells in colonic lamina propria in patients with inflammatory bowel disease.

Adolescent↗
PubMed2001

Interpretation of ileal biopsies: morphological features in normal and diseased mucosa.

One of the advantages of flexible colonoscopy is that the terminal ileum can easily be reached and biopsied by an experienced operator. Thus, the pathologist will, with increasing frequency, receive ileal biopsies from patients who have or may not have ileal disease and it is therefore useful to have a good knowledge of the spectrum of ileal mucosal histology and pathology, of its normal function, and of the changes seen in different conditions. It is also desirable to be aware of diseases that occur less frequently. The ileal microscopic features are related to its absorptive function on the one hand, and to non-specific and specific defence mechanisms of the organism against potential hazardous components on the other. As a consequence the mucosa features a constant physiological and controlled inflammatory process. Part of the ileal mucosal structure is determined by the presence of the gut-associated lymphoid tissue (GALT) which plays a key role in discriminating harmless nutrients and harmful pathogens. It will be important to distinguish this normal situation from alterations seen in infectious or inflammatory pathology. Further, because of the therapeutic implications, it is necessary that acute and chronic (idiopathic) inflammation are recognized. This will in general be possible by evaluating the composition of the inflammatory infiltrate and the occurrence of epithelial and mucosal architectural changes.

Biopsy↗
PubMed2001

New treatment options in spondyloarthropathies: increasing evidence for significant efficacy of anti-tumor necrosis factor therapy.

Tumor necrosis factor-alpha is a major effector and regulatory cytokine, which seems to have an outstanding position in rheumatic and other inflammatory states. Because TNF-alpha has been detected in the inflamed gut and sacroiliac joints of patients with chronic inflammatory bowel diseases and spondyloarthritides, like ankylosing spondylitis, there was need for studies of the efficacy of the modern biologic anti-TNF agents infliximab and etanercept in these diseases. Infliximab is approved for the treatment of Crohn disease. In addition, there are now also positive data for infliximab in the treatment of ankylosing spondylitis and for etanercept and infliximab in the treatment of psoriatic arthritis.

Antibodies, Monoclonal↗
PubMed2001

Flow cytometric analysis of gut mucosal lymphocytes supports an impaired Th1 cytokine profile in spondyloarthropathy.

OBJECTIVE: To quantify the fraction of gut mucosal lymphocytes expressing the T helper type 1 (Th1) cytokines, interferon gamma (IFNgamma) and interleukin (IL)2, and the Th2 cytokines, IL4 and IL10, at the single cell level in patients with spondyloarthropathy (SpA) in comparison with healthy controls. METHODS: An improved extraction protocol was used for the enrichment of intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) from colonic and ileal biopsy specimens obtained from patients with SpA (n=20) and healthy controls (n=13). After stimulation with phorbol ester/ionomycin, expression of the intracellular cytokines IFNgamma, IL2, IL4, and IL10 was determined in CD3+, CD3+CD8+ and CD3+CD8- T cells by flow cytometry. RESULTS: In colonic LPLs, a significant decrease in IFNgamma-producing CD3+ cells was observed (p=0.02) in patients with SpA. In the CD3+CD8- subset, the proportion of cells producing IFNgamma and IL2 was decreased in patients with SpA (p=0.021 and p=0.027 respectively). In ileal LPLs, the percentage of IL10-producing CD3+CD8- cells was significantly increased (p=0.046). CONCLUSION: An impaired Th1 cytokine profile is observed in gut mucosal lymphocytes from patients with SpA. This adds to the existing evidence that the gut mucosal immune apparatus is involved in the pathogenesis of SpA.

Adult↗
PubMed2001

Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFalpha.

OBJECTIVES: To evaluate the effect of anti-TNFalpha on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry. RESULTS: At baseline the percentage of T cells positive for IFNgamma (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while IL10 (p=0.001) was increased. This cytokine profile, confirmed by the mean fluorescence intensities (MFI), was more pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK T cells, characterised by high IL4 and IL10 numbers, were also increased in patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFNgamma and IL2 in patients with SpA. Moreover, there was a transient decrease in IL10 and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. This switch in cytokine profile was seen in both the CD3+/CD8- and CD3+/CD8+ subsets. CONCLUSIONS: Before treatment patients with SpA had an impaired Th1 cytokine profile compared with healthy controls and patients with RA. TNFalpha blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the effect of anti-TNFalpha on the immune changes in SpA, and provide insights into the mechanisms involved in TNFalpha blockade.

Adult↗
PubMed2001

Current use of biologicals for the treatment of spondyloarthropathies.

Spondyloarthropathies (SpA) are a group of related disorders. The hallmark symptoms include spondylitis, pauci-articular synovitis and enthesiopathy. In an important number of cases, subclinical gut inflammation with pathological findings resembling Crohn's disease can be found. Some of these patients may eventually develop overt Crohn's disease. Conventional medical therapy in patients with SpA consists of non-steroidal anti-inflammatory drugs (NSAIDs). Sulphasalazin can be co-administered, especially in cases of chronic synovitis or enthesiopathy. Recently, experience with anti-TNF-alpha monoclonal antibodies (infliximab), a new class of biological compounds, has opened new avenues for treating patients with SpA. In particular, infliximab used in two open studies gave significant benefit on the locomotor manifestations in patients with Crohn's disease, in patients with ankylosing spondylitis, undifferentiated SpA and psoriatic arthritis. Etanercept, another TNF-alpha antagonist (soluble receptor), was shown to induce benefit in a placebo-controlled study in patients with psoriatic arthritis. The relationship between SpA and inflammatory bowel disease lead to the hypothesis that interfering with gut inflammation in patients with SpA would yield a potential target for modulating the synovitis in these patients. Thus, besides TNF-alpha blockade, other strategies with potential efficacy can be envisioned, such as IL-10, ICAM-1 antisense or anti-(4)beta(7) antibodies.

Adjuvants, Immunologic↗