Showing papers by "Maxime Dougados published in 2001"

Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis.

Abstract: Objective To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs). Methods Patient data from 5 short-term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple items in the 5 outcome domains for AS treatment: physical function, pain, spinal mobility, patient global assessment, and inflammation. At least one measure per domain was responsive (standardized response mean of >0.5), except for the spinal mobility domain, which was omitted from the criteria. We developed and tested candidate improvement criteria in a random two-thirds subset from the 3 largest trials and used the remaining one-third for validation. These 3 largest trials included 923 patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of ≤25%. Results Candidate definitions were changes in single domains and in multiple measure indices, as well as combinations of improvements in multiple domains. Worsening in a domain was defined as a change for the worse of ≥20% and a net change for the worse of ≥10 units on a scale of 0–100. Partial remission (for comparison purposes) was defined as an end-of-trial value of <20/100 in each of the 4 domains. Among 20 candidate criteria, change of ≥20% and ≥10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; χ2 = 36.4, P < 0.001). Results were confirmed in the validation subset. Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement rates using this criterion were 49% for NSAID-treated patients and 24% for placebo-treated patients. Conclusion Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy-to-use measure of short-term improvement in AS.

Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial

Abstract: Objective To evaluate the ability of diacerein, an interleukin-1β inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA). Methods In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1-mm–graduated magnifying glass. Results Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent-to-treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean ± SD 0.18 ± 0.25 mm/year versus 0.23 ± 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel habits. Conclusion This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.

Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study.

Abstract: Objective To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). Methods A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. Results The change in the total radiologic score for the patients followed up over 3 years was a mean ± SD increase of 6.1 ± 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA–DRB1∗04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti–heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA–DRB1∗01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1∗04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1∗04 genes, and erosions score at baseline. Conclusion Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.

Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.

Abstract: Objective To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2–specific inhibitor, in the treatment of ankylosing spondylitis (AS). Methods The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain ≥40 mm on a 100-mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]). Results Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were −13 mm, −21 mm, and −27 mm (P = 0.006) for pain and 1, −6, and −12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively. Conclusion The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS.

Changes in bone density in patients with ankylosing spondylitis: a two-year follow-up study.

Abstract: The objectives of the study were to determine the 2 year rate of bone changes in patients with ankylosing spondylitis (AS) and, whether bone loss is related to physical impairment, systemic inflammation, and therapy. Consecutive outpatients fulfilling the modified New York criteria for AS were included. Baseline assessment included age, disease duration, treatment, clinical, radiologic and laboratory data. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined every 6 months. Persistent systemic inflammation was defined as mean ESR ≥ 28 mm/h or mean CRP ≥ 15 mg/l. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry, at baseline and year 2. Statistical analysis compared the baseline and 24 month follow-up BMD data, and determined whether baseline data, and persistent systemic inflammation during the 2 years, were related to the 24 month percentage changes in BMD. Fifty-four patients (35 men, 19 women; mean age 37.3 ± 11.3 years, mean disease duration 12.4 ± 8.6 years) were included. After 2 years, BMD did not change at the lumbar spine (+0.75%± 3.5, p= 0.23), and decreased at the femoral neck (–1.6%± 4, p= 0.006). The 24 month percentage change in femoral neck BMD was related to persistent systemic inflammation, defined using ESR (mean percentage change –4.1%± 5.7 and –1.2%± 3.9 in patients with and without persistent inflammation; respectively; p= 0.007). These results suggest that persistent inflammation might be an etiologic factor of bone loss in AS.

Ultrasonic backscatter and transmission parameters at the os calcis in postmenopausal osteoporosis.

Abstract: Ultrasound technology has emerged as a new tool in the assessment of osteoporosis. Ultrasound parameters usually are measured in transmission; there is a potential for the analysis of backscattered signals to provide information on bone microarchitecture. The aim of this study was to explore a new technological development of the method, adding backscatter coefficient to transmission parameters, and to examine the appropriate thresholds to identify postmenopausal osteoporotic women. We examined 210 postmenopausal women (including 60 with osteoporotic fractures) and 30 healthy premenopausal controls. They had lumbar spine and hip bone mineral density (BMD) measurement and quantitative ultrasound (QUS) evaluation at the os calcis, measured in transmission (broadband ultrasound attenuation [BUA], speed of sound [SOS], ratio of transit time [dt] to BUA [dt/BUA], and "strength" index [STI]) and reflexion (broadband ultrasound backscattering [BUB]). The standardized CVs (sCVs) were between 2.27 % and 3.40 % for QUS measured in transmission and 4.41% for BUB. The odds ratio (OR) for fracture discrimination adjusted for age was 2.77 for hip BMD and between 1.6 and 2.9 for QUS. After adjustment for hip BMD, ORs were still highly significant for SOS, STI, and dt/BUA. According to hip BMD T score, prevalence of osteoporosis in our population was 39%. To detect the same prevalence, T scores ranged between -0.95 and -1.42 for QUS. QUS parameters have adequate ability to discriminate osteoporotic patients from controls. The World Health Organization (WHO) threshold for diagnosis of osteoporosis does not apply to this technology. The clinical utility of BUB at the os calcis, in addition to usual ultrasound parameters, is not yet proven. However, BUB evaluation, which does not require two transducers and may be implemented in conventional reflection mode systems, warrants further studies.

Concomitant therapy: an outcome variable for musculoskeletal disorders? Part 2: total joint replacement in osteoarthritis trials.

Abstract: Interest has grown in using the requirement of total joint replacement (TJR) as a "hard" outcome measure. Limitations exist, however, in the use of such an outcome, in particular the variability in the decision to perform surgery, length of surgical waiting lists, and sensitivity to change. This special interest group is exploring ways of retaining the clinical relevance of TJR but overcoming the problems--2 alternative outcomes are being considered: "time to physician's decision to recommend surgery" and "time to fulfilling criteria for total joint replacement."

Phenotypic diversity is not determined by independent genetic factors in familial spondylarthropathy.

Abstract: Objective To analyze the segregation of manifestations belonging to the spectrum of spondylarthropathy (SpA) among patients and unaffected siblings within SpA multiplex families. Methods Ninety-five multiplex families have been investigated. The diagnosis of SpA was made according to European Spondylarthropathy Study Group criteria. The prevalence of SpA manifestations was determined in unaffected siblings and compared with their prevalence in patients. Results We compared 241 SpA patients with 259 unaffected siblings. The prevalence of skeletal and extraarticular features not used as diagnostic criteria, i.e., radiographic sacroiliitis, peripheral enthesitis, uveitis, psoriasis, and inflammatory bowel disease, was significantly increased in patients compared with unaffected siblings. This result was not accounted for by sex or HLA–B27 distribution differences. Conclusion In familial SpA, skeletal and extraarticular manifestations tend to segregate together, implying that all subsets are predominantly determined by a shared component, and that accessory factors must be responsible for phenotype diversity.

Measurement of joint space width in hip osteoarthritis: influence of joint positioning and radiographic procedure.

Abstract: Objectives. We assessed the influence of patient positioning and radiographic procedure, and defined a smallest detectable difference (SDD) in hip osteoarthritis (OA). Methods. OA hip patients each had a standardized pelvic radiograph and, 5 min later, a modified pelvic radiograph with the feet internally rotated 5 (part 1 of the study), the X-ray beam centred on the umbilicus (part 2), or another standardized pelvic radiograph (part 3). Results. Corresponding mean differences in joint space width (JSW) measurements (limits of agreement) between views were + 0.03 (- 0.53 to + 0.59), - 0.31 (- 1.15 to + 0.53) and - 0.02 ( - 0.48 to + 0.44) mm. The two views differed significantly in mean JSW in part 2 of the study (P = 1.6 x 10 -4 ), but not in part I (P = 0.375) and part 3 (P = 0.580). The SDD estimate was 0.46 mm. Conclusions. Modifying the X-ray beam and foot rotation increases variability in JSW measurements. Use of urograms to evaluate radiological progression should be avoided. A change greater than 0.46 mm could define radiological hip OA progression.

Towards a definition of "difference" in osteoarthritis.

Abstract: To assess existing information regarding detectable differences in osteoarthritis (OA), a systematic literature search was conducted up to December 1999. Thirty-three articles were considered methodologically relevant to the definition and categorization of detectable differences in OA. It was determined that the musculoskeletal literature contains a wealth of information that relates to observed changes, much of which is derived from the clinical trials literature, but there have been relatively few methodological studies that have systematically evaluated the nature, categorization, and relevance of the change. Furthermore, most of those that have been published take the perspective of an individual or groups of experts other than that of the patient. This summary of the current literature reveals that the diverse sources of information go part way towards developing an understanding of detectable differences and their importance in the area of OA research and clinical practice. Stakeholders' interests as well as factors that modulate perceptions of importance need to be taken under consideration. In particular, the patient's perspective of the importance of change at an individual level requires further evaluation. This area of clinical research is relatively underdeveloped, but there is considerable opportunity for progress.

Evidence-based management of osteoarthritis: practical issues relating to the data.

Abstract: Osteoarthritis (OA) is a major cause of pain and disability in the elderly. The perspective of OA as a dynamic process triggered by diverse insults is increasingly accepted. Objectives of management are patient education, relief of pain, optimization of function and modification of the OA process. Management should be individualized and should take into account factors relating to the person as well as the OA joint. There is a reasonable evidence base for several key elements of management. Recent review of the research evidence shows a skewed distribution in favour of drugs, particularly NSAIDs, and important gaps in clinically relevant knowledge. The restricted generalizability of the research data could be improved by improvements in study design and methods of reporting. Current published guidelines on management of OA are critically reviewed and compared.

Diacerein as a disease-modulating agent in osteoarthritis.

Abstract: This paper reviews the most recent clinical and experimental studies on diacerein, both of which are under investigation. Diacerein could be a disease-modulating agent in osteoarthritis because structural benefits have been reported in recent trials. Moreover, after an empirical use, studies return to the experimental field to understand the mechanism of action of this molecule. However, clinical trials using new sets of criteria could be conducted to estimate the structural modulating effect of diacerein; experimental studies must be performed to understand this effect.

Exercise therapy in patients with osteoarthritis of the hip or knee

Abstract: Exercise therapy has clearly demonstrated its efficacy in the secondary prevention of knee or hip osteoarthritis. A program of exercises to be performed at least three times a week should be systematically considered in patients with knee or hip osteoarthritis. The exercises should be considered with regard to the level of symptoms of the patients (inflammatory episode of the disease versus chronic “mechanical” pain). The mode of administration (ie, in the hospital vs at home) and the specific role of the different persons intervening in such programs (ie, nurses, physiotherapists, doctors) must be further studied.

Densitométrie osseuse et ostéoporose post-ménopausique

Abstract: L'osteoporose est une maladie diffuse du squelette caracterisee par une diminution de la masse osseuse et une alteration de la microarchitecture du tissu osseux, entrainant une augmentation de la fragilite osseuse et du risque de fracture [1]. Cette definition leve l'ambiguite du diagnostic de cette maladie longtemps definie par sa complication : la fracture. Elle met aussi en evidence les deux composantes de la fragilite osseuse : la quantite et la qualite. Cette derniere depend de nombreux parametres : micro-architecture, qualite du collagene et des micro-cristaux, capacite de reparation des micro-fractures... Aucun de ces parametres n'est accessible aujourd'hui a une mesure non invasive. Lors de l'usage de la densitometrie l'evaluation de la solidite osseuse est seulement quantitative. In vitro, la densite osseuse ainsi mesuree explique 75 a 85 % de la variance de la resistance vertebrale jugee par la force de resistance a la rupture en compression [2]. Ces methodes ont fait des progres techniques considerables, ont permis d'etablir une definition densitometrique de l'osteoporose, et ont modifie la prise en charge des patients. Dans la pratique, l'indication de ces mesures doit etre discutee a l'echelle individuelle en fonction des autres facteurs de risque de fracture [3, 4].