Biomedical subjects

J-P Devogelaer

Publications and source records attributed to J-P Devogelaer.

8 recordsLinked to original sources

PubMed2005

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study.

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.

Adult↗

PubMed2005

Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis.

OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working group to assess the value of time to joint surgery as a potential therapeutic failure outcome criterion for osteoarthritis (OA) of the hip or knee in the assessment of potential structure modifying agents. METHODS: PubMed was searched for manuscripts from 1976 to 2004. Relevant studies were discussed at a 1-day meeting. RESULTS: There are no accepted guidelines for 'time to' and 'indications for' joint replacement surgery. A limited number of trials have examined joint replacement surgery within the study population. Several parameters, particularly joint space narrowing (interbone distance), correlate with surgical intervention. However, at the level of the knee, none of the parameters have positive predictive value for joint replacement surgery better than 30%. In contrast, lack of significant joint space narrowing has a strong negative predictive value for joint replacement surgery (>90%), that remains after controlling for OA pain severity. CONCLUSION: At this time, GREES cannot recommend time to joint surgery as a primary endpoint of failure for structure modifying trials of hip or knee OA-as the parameter has sensitivity but lacks specificity. In contrast, in existing trials, a lack of progression of joint space narrowing has predictive value of >90% for not having surgery. GREES suggests utilizing joint space narrowing (e.g., >0.3-0.7 mm) combined with a lack of clinically relevant improvement in symptoms (e.g., >/=20-25%) for 'failure' of a secondary outcome in structure modifying trials of the hip and knee.

Antirheumatic Agents↗

PubMed2005

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades.

Administration, Oral↗

PubMed2004

Evaluation of the role of the SQSTM1 gene in sporadic Belgian patients with Paget's disease.

A positional cloning effort in French Canadian families with Paget's disease of bone (PDB) resulted in the identification of a mutation in the sequestosome1 (SQSTM1) gene in a subset of both familial and sporadic PDB cases. This was confirmed in samples of mainly United Kingdom (UK) origin. In this study, we performed both mutation analysis and association studies in order to evaluate the role of this gene in a collection of isolated Belgian PDB patients. A mutation in the SQSTM1 gene was found in only 6 of 111 patients (5.4%). In all cases it involves the P392L mutation, previously shown to be common in both familial and sporadic cases. To perform association studies, we selected 8 single nucleotide polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these. Haplotype analysis indicated that typing of 3 Tag SNPs (IVS1 + 633A/C, IVS5 - 23A/G, and 976A/G) enables us to identify the most common haplotypes. Association studies for the 3 selected SNPs, based on 105 PDB cases without a SQSTM1 mutation and 159 control individuals, did not support a possible influence of natural variants in the SQSTM1 gene either on the pathogenesis of PDB or on the disease severity. In conclusion, our study confirms that the P392L mutation is a recurrent mutation causing PDB in different populations. We were not able to show an association between SQSTM1 polymorphisms and PDB in our population but this clearly needs to be extended to other populations. The presented identification of haplotype Tag SNPs will be of major help for such studies.

Adaptor Proteins, Signal Transducing↗

PubMed2004

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment.

OBJECTIVES: To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. METHODS: Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6. RESULTS: Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (p<0.05). None of the QoL scales improved with MP treatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP. CONCLUSION: This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres.

Adult↗

PubMed2003

Patient assessment using standardized bone mineral density values and a national reference database: implementing uniform thresholds for the reimbursement of osteoporosis treatments in Belgium.

Dual-energy X-ray absorptiometry (DXA) devices from the three main manufacturers provide different bone mineral density (BMD) values, due in part to technical differences in the algorithms for bone mineral content (BMC) and area measurements and in part to the use of different manufacturer-derived reference databases. As a result, significant differences exist between Hologic, Lunar and Norland systems in the reported young normal standard deviation scores or T-scores. In a number of European countries, including Belgium, a T-score below -2.5 is one of the key criteria for reimbursement of osteoporosis treatments. This paper addresses the first attempt to implement a nationwide, uniform expression of BMD in patients, in order to harmonize drug reimbursement. To this end, measures were taken to implement a uniform expression of BMD in Belgian patients, by converting each manufacturer's absolute BMD to standardized BMD (sBMD) values and by establishing a single national reference range.

Absorptiometry, Photon↗

PubMed2002

Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis.

OBJECTIVE: We previously described a novel radiolabelled monoclonal antibody (1.2B6), which reacts with porcine E-selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on (111)In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with (99m)Tc in patients with rheumatoid arthritis (RA) by comparison with (i) (111)In-labelled 1.2B6 F(ab')(2) and (ii) conventional bone scanning. METHODS: (99m)Tc-1.2B6-Fab ( approximately 440 MBq) and (111)In-1.2B6-F(ab')(2) ( approximately 27 MBq) were compared in 10 patients using a double-isotope protocol. Images were obtained 4 and 20-24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, (99m)Tc-1.2B6-Fab and (99m)Tc-oxidronate ((99m)Tc-HDP) ( approximately 740 MBq) were compared on the basis of visual and semi-quantitative analysis of joint uptake (joint/soft tissue ratios) 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared. RESULTS: Image contrast was slightly better with (99m)Tc-Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76% for both fragments at 24 h. Plasma clearance of (99m)Tc-Fab was faster than that of (111)In-F(ab')(2) (t(1/2) 142 vs 421 min; P<0.0001). (99m)Tc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of (99m)Tc-Fab was 88%, higher than that of (99m)Tc-HDP (57%) as a result of the low specificity of the latter in RA. Receiver operating characteristic (ROC) curve analysis using joint/soft tissue ratios as a variable cut-off showed that (99m)Tc-Fab discriminates better than (99m)Tc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of (99m)Tc-Fab was observed by inactive or normal joints, whereas (99m)Tc-HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult. CONCLUSION: (99m)Tc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than (99m)Tc-HDP bone scanning. The advantages over (111)In-1.2B6-F(ab')(2) are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.

Adult↗

PubMedDate not supplied

Bone disorders after organ transplantation.

Three main bone disorders may occur after organ transplantation: epiphyseal impactions, avascular bone necrosis, and osteoporosis. Their main clinical characteristics, causes, diagnostic approaches, and therapies are discussed in this review.

Bone Diseases↗