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Biomedical subjects

M Dougados

Publications and source records attributed to M Dougados.

340 records · Page 19Linked to original sources

Infliximab in spondylarthropathy--influence on bone density.

Osteoporosis is frequently associated with Ankylosing Spondylitis (AS). Bone mineral density (BMD) decreased predominantly in patients with active disease. Moreover, conventional therapy, i.e. NSAID seems to have no influence in the bone loss. It has been suggested that local or systemic inflammatory cytokine release might be implicated in bone loss. Monoclonal antibody to TNFalpha in patients with AS demonstrated significant clinical response with significant reduction in the acute-phase reactants ESR and CRP. We evaluated the changes in bone mineral density (BMD) in patients with Spondylarthropathy (SpA) treated with infliximab (a human/mouse neutralising chimeric monoclonal antibody). We included 29 patients. In 6 months, there was a statistically significant increase in BMD both at the spine and total hip. There was an increase in osteocalcin between baseline and week 6. These data suggest a benefit of anti-TNFalpha therapy on BMD in patients with SpA, may be through an uncoupling effect on bone cells.

Adult↗

Primary glenohumeral degenerative joint disease: factors predisposing to arthroplasty.

OBJECTIVE: To evaluate the natural history of shoulder osteoarthritis (OA), in particular the requirement for arthroplasty over time, and to determine the potential predisposing factors for such arthroplasty. METHODS: In- and out-patients with the diagnosis of OA of the shoulder seen between January 1990 and December 1994 were contacted by mail or telephone in 2000. Evaluation at the time of diagnosis: demographics, clinical and radiological data were evaluated at the time of diagnosis. The follow-up evaluation consisted of a questionnaire sent to each patient inquiring whether they had had recourse to shoulder arthroplasty and, if not, evaluated their willingness regarding this surgical approach. For the statistical analysis the requirement for arthroplasty over time was evaluated using the Kaplan-Meier technique. Potential factors predisposing to arthroplasty were determined using a Cox-model analysis. RESULTS: The questionnaire was answered by 72 of the 86 contacted patients. No difference was observed in clinical and radiological variables at the time of diagnosis between responders and non-responders. The requirement for arthroplasty was low (respectively 5% and 13%, 5 and 10 years following the onset of the symptoms). Nearly half of the patients who had not undergone surgery thought that arthroplasty would have been the treatment of choice to improve their quality of life since more than one year at the time of completing the questionnaire. Two variables were picked up in the Cox analysis, with a probability of shoulder replacement higher in patients with concomitant osteonecrosis of the humeral head (p = 0.02) and a non-eccentric glenohumeral OA (p = 0.011). CONCLUSION: The low percentage of patients with arthroplasty over time, together with patient perception, suggest underuse of this surgical approach in shoulder OA.

Aged↗

Combination therapy in early rheumatoid arthritis.

The course of rheumatoid arthritis (RA) is determined early and the goals in early RA are to prevent radiologic joint degradation and to achieve optimal clinical and biological remission. Achieving these goals means that many RA patients may be candidates for combination disease-modifying therapy. We review data from randomized clinical trials regarding the impact of these treatment strategies as the initial therapy in early RA. It appears likely that the place of combination therapy will increase in the coming decades, even in very early RA patients, where the ultimate goal is persistent remission.

Adult↗

HLA DRB1*01 and DRB1*04 phenotyping does not predict the need for joint surgery in rheumatoid arthritis. A retrospective quantitative evaluation of 300 French patients.

OBJECTIVE: To determine if the presence of HLA-DR disease-associated epitopes predicts the need for total joint arthroplasty or joint fusion in rheumatoid arthritis (RA). METHODS: Tertiary-referral, monocenter study. Three hundred RA patients (1987 ACR criteria) were retrospectively evaluated; outcome measure was recourse to total joint arthroplasty, joint fusion or bone resection. HLA-DR1 and DR4 were considered as the disease-associated epitopes (subtypes were not available for analysis). Analysis was performed using the lifetable method (Kaplan-Meyer technique). RESULTS: Of the 300 patients included, 78% were women, mean age: 56+/-14 years, mean RA follow-up: 12+/-9 years. Phenotyping: 73% of patients carried one (52%) or two (21%) disease-associated epitopes. Surgery was performed on 24% of the patients during follow-up. The most frequent surgery was total hip arthroplasty (13% of patients). According to lifetable analysis, 13% of patients had surgery (total joint arthroplasty or joint fusion) after 10 years of follow-up, 34% after 20 years. years of follow-up, There was no statistically significant difference in recourse to surgery according to absence or presence (single or double-dose) of disease-associated epitopes. Similar results were observed if the event was the second surgical procedure on a given patient. CONCLUSION: This study failed to demonstrate a relation between HLA phenotyping and the severity of RA defined by the requirement for surgery.

Adolescent↗

Benefit/risk of combination therapies.

It is now accepted that rheumatoid arthritis is not a benign disease, and has considerable morbidity and increased mortality rates. Monotherapy with disease modifying anti-rheumatic drugs (DMARDs) is often ineffective, and rarely leads to sustained clinical remission. Many clinical trials suggest the effectiveness of using combination therapies, and also the benefit of aggressive management early in the course of the disease. However, recent publications studying a variety of combination therapies in rheumatoid arthritis have shown diverse results. Drug combinations at an early stage of rheumatoid arthritis which slow radiographic progression appear to be the most convincing. These data suggest that practitioners should begin with intensive therapy in early disease, and not reserve combination therapy for those who fail monotherapy. The therapeutic strategy should be positioned according to the severity of the disease: in RA with markers indicating severity, combination should be initiated at the start of therapy while it should be instituted in a rapid step-up fashion in mild RA if insufficient efficacy is seen for monotherapy. In general, combinations appear safe and well-tolerated, but continued caution with appropriate monitoring of long-term results and possible toxicities is required.

Antirheumatic Agents↗

How to define a Minimal Clinically Individual State (MCIS) with pain VAS in daily practice for patients suffering from musculoskeletal disorders.

OBJECTIVES: Pain is frequently the primary variable in symptomatic clinical trials for the evaluation of rheumatological disorders. The protocol of such trials mention a minimum level of pain as an entry criterion [e.g. a level above the Patient Acceptable Symptoms State (PASS)] and the changes in pain as the primary variable. Usually, the results are expressed at a group level as the mean changes in pain. However, the presentation at an individual level and, in particular, the percentage of patients with a Low Disease Activity State at the end of the study seems more clinically relevant. Pain is usually evaluated using a continuous variable such as a 0-100 visual analogue scale. The cut-offs permitting one to define both the entry criterion and the LDAS are not well established. The objective of this study was to evaluate such cut-offs using a patient-derived perspective. METHODS STUDY DESIGN: cross-sectional study. PATIENTS: consecutive out patients suffering from chronic rheumatic diseases familiar with the use of a VAS to evaluate their level of pain. DATA COLLECTED: two questions were asked the patients at the end of the visit: "Based on the experience you have because of your chronic rheumatic disorder, could you please specify the level of pain below which you consider your disease as inactive ? Moreover, could you please also specify the level of pain above which you consider taking a pain killer?" Before answering the second question, it was explained to the patient that their answer to the second question could be similar to their response to the first one. For the two questions, the cumulative percentage of patients (disease inactive and pain killer intake) were calculated for each level of pain. RESULTS: The underlying disease of the 137 evaluated patients (mean age: 57+/-16 and female sex: 76%) was rheumatoid arthritis (n = 59), ankylosing spondylitis (n = 19), SLE (n = 2), back pain (n = 20), or peripheral osteoarthritis (n = 37). The mean disease duration was 12+/-10 years. At the time of the study, the current level of pain evaluated on a 0-100 VAS was 33+/-22. The LDAS was 49, 36 and 25 for our patient population at the 25th, 50th and 75th percentiles, respectively. The pain killer intake level was 32, 48, 64 at the 25th, 50th, 75th percentile respectively. CONCLUSION: This study suggests that LDAS and PASS may be distinct concepts. The methodological approach adopted here could be of interest for specifying the minimum level of symptoms at entry in a symptomatic trial (PASS) and also to present results in terms of the percentage of patients in good condition (LDAS) at the end of a trial.

Arthritis, Rheumatoid↗

Leflunomide in rheumatoid arthritis in daily practice: treatment discontinuation rates in comparison with other DMARDs.

OBJECTIVE: To evaluate the treatment discontinuation rate of leflunomide in rheumatoid arthritis (RA) in comparison with the discontinuation of other disease modifying anti-rheumatic drugs (DMARDs), in daily practice, in a single center and during the same period of time. METHODS STUDY DESIGN: 3-year, retrospective, monocenter. PATIENTS: RA patients for whom leflunomide or another DMARD was initiated between 1998 and 2001 (several DMARDs could be initiated for a given patient during this period). Collected data: For each patient, demographic and disease data. For each treatment course, date of initiation, if relevant date of discontinuation and reason for discontinuation. ANALYSIS: Percentage of patients discontinuing treatment over time (life table method; Kaplan-Meier), comparison between leflunomide and the "any other DMARD" or methotrexate groups using the Log-Rank test. RESULTS: During the study period, 515 DMARDs were initiated in 285 patients. Leflunomide was initiated in 161 patients who were older and had a longer disease duration than the other treated patients (59 +/- 13 years and 14 +/- 9 years versus 54 +/- 15 years and 11 +/- 10 years in the leflunomide group and other DMARDs group respectively). Discontinuation rate of leflunomide after 1 year was 56.7%, mainly because of adverse drug reactions (41.6%). The discontinuation rate whatever the reason and for toxicity was higher for leflunomide than for other DMARDs studied. However discontinuation for inefficacy was similar in both groups. CONCLUSION: This study conducted in conditions of daily practice when leflunomide was first available suggests a higher discontinuation rate of leflunomide because of adverse events when compared to other DMARDs.

Adjuvants, Immunologic↗

Proposed guidelines for the clinical evaluation of interleukin-1 inhibitors in the treatment of rheumatoid arthritis.

Since the effects of interleukin-1 might contribute to the lesions observed in rheumatoid arthritis. a compound which inhibits this cytokine should be an important addition to the therapeutic agents available for use in this disease. Clinical evaluation of such a compound must answer the following questions: Is the proposed drug "quick" or "slow" acting on the clinical and/or biological symptoms of inflammation? Is the proposed drug able to prevent and/or to stop the cartilage damage in rheumatoid arthritis? We propose some methodological guidelines for clinical trials designed to assess these compounds.

Analgesics↗

Blood polymorphonuclear behavior in patients with ankylosing spondylitis.

The oxidative metabolism and chemotaxis of polymorphonuclear leukocytes (PMNs) collected from patients with ankylosing spondylitis and healthy subjects were studied in parallel. The responses to opsonized zymosan were significantly lowered considering oxygen consumption and release of superoxide anions, whereas no modification of these parameters to phorbol myristate acetate and calcium ionophore (A 23187) stimulations were observed. A seric factor was not involved but the characterization of a specific intrinsic abnormality of the PMNs needs further investigations. PMN chemotaxis, assessed by two methods performed in parallel, remained unchanged.

Adult↗

[Monocytic arthritis. Study of their clinical significance apropos of 43 cases].

The clinical significance of synovial monocytosis (greater than 50 p. cent) of inflammatory fluids (greater than 1,000 elements per mm3) was studied retrospectively in 43 patients. An accurate diagnosis was made 35 times: rheumatoid polyarthritis (13 cases), lupus disease (1 case), Gougerot-Sjögren syndrome (1 case), isolated infantile monoarthritis (1 case), sarcoidosis (1 case), seronegative spondylo-arthropathy (3 cases), microcrystalline arthritis (5 cases) arthritis revealing a blood disease (2 cases), idiopathic "lymphocytic" arthritis (3 cases), eosinophilic pseudo-allergenic arthritis (2 cases), aseptic osteonecrosis of the medial condyle (1 case), femoro-patellar arthrosis (1 case). Among the 8 other patient for whom no diagnosis was made, 6 had a spontaneously resolving acute affection, evoking the possibility of a viral etiology.

Adult↗

[Aseptic arthritis after total knee prosthesis].

In 3 patients who developed acute arthritis of the knee 3 months to 5 years after insertion of a total condylar prosthesis, it was possible to formally exclude an infectious cause. A number of cytological and histological arguments confirm that these were cases of foreign body arthritis (polyethylene debris and metal dust). These cases of arthritis responded to local steroid treatment combined with a Yttrium synoviorthesis, in the absence of any antibiotic treatment. The synoviorthesis was performed in order to eliminate the real foreign body granuloma which develops and which can contribute to the loosening of these prostheses.

Adult↗

Cyclosporin in rheumatoid arthritis.

Rheumatoid arthritis is present in a population which is heterogeneous both clinically and immunologically. A variety of cells including lymphocytes, macrophages and fibroblasts play important roles in its pathogenesis, but the T cell appears to be a common thread throughout the disease process. Treatments aimed at reducing these lymphocytes mechanically and specifically result in a good clinical response in many patients. The mechanism of action of cyclosporin A (CyA) in inhibiting T lymphocytes presents a more specific form of therapy. The effects of CyA on the activity of RA have mainly been investigated in patients with active, refractory long-term disease. The data obtained in these trials suggest that CyA is not only a symptomatic treatment for RA but can also be considered a DMARD. The potential benefits of CyA on the one hand and its potential toxicity on the other indicate that a careful assessment should be made of its use in patients with early active RA.

Arthritis, Rheumatoid↗