Showing papers by "Maxime Dougados published in 2007"

Safety and Efficacy of Additional Courses of Rituximab in Patients With Active Rheumatoid Arthritis An Open-Label Extension Analysis

Abstract: Objective To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA). Methods An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of ≥8 with ≥16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure. Results A total of 1,039 patients received ≥1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20 responses were comparable at week 24 after course 1 and at week 24 after course 2 (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good responses were also comparable in course 2 relative to course 1 (88% versus 79%), with EULAR remission occurring in a 2-fold higher proportion of patients after course 2 than after course 1 (13% versus 6%). The most common adverse events, which were mild-to-moderate acute infusion-related events, decreased with each course. The serious infection rate after course 1 (5.1 per 100 patient-years) remained stable through additional courses. The proportion of patients with circulating IgM and IgG levels below the lower limit of normal (LLN) increased with subsequent courses; however, serious infection rates in these patients (5.6 per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient-years in patients with low IgG levels were comparable with those in patients with immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present additional safety concerns. Conclusion These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.

Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy

Abstract: Objective: To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis. Methods: Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept ∼10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years. Results: 317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (⩽3.2) and DAS28 (C-reactive protein)-defined remission ( Conclusion: No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease. Trial registration number: NCT00124982.

Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders.

Abstract: The concepts of minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS) could help in interpreting results of trials involving patient-reported outcomes by translating the response at the group level (change in mean scores) into more clinically meaningful information by addressing the patient level as "therapeutic success (yes/no)." The aims of the special interest group (SIG) at OMERACT 8 were to discuss specific issues concerning the MCII and PASS concepts, especially the wording of the external anchor questions used to determine the MCII and PASS estimates, and to move toward a consensus for the cutoff values to use as the MCII and PASS in the different outcome criteria. The purpose of this SIG at OMERACT 8 was to inform participants of the MCII and PASS concepts and to agree on MCII and PASS values for pain, patient global assessment, and functional impairment.

Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis.

Abstract: Objective In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS) Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS Methods We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3) The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS) Results Complete data were available on 97 patients Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression ( 029, P 0004) Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 94 [95% confidence interval 16–56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 186 [95% confidence interval 25–138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R 2 50%) MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units) Conclusion These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage

Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis

Abstract: Objective: Evaluate long-term safety and efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). Methods: Patients with AS who previously participated in a randomised controlled trial (RCT) of etanercept were eligible to enrol in a 168-week open-label extension (OLE). Safety end points included rates of adverse events (AE), serious adverse events (SAE), infections, serious infections and death. Efficacy end points included Assessment in Ankylosing Spondylitis (ASAS20) response, ASAS 5/6 response and partial remission rates. Results: A total of 257 of 277 patients (92%) enrolled in the OLE. After up to 192 weeks of treatment with etanercept, the most common AEs were injection site reactions, headaches and diarrhoea. The exposureadjusted rate of SAEs was 0.08 per patient-year. The rate of infections was 1.1 per patient-year, and the rate for serious infections was 0.02 per patient-year. No deaths were reported. Of patients who received etanercept in both the RCT and OLE and were still in the trial, 71% were ASAS20 responders at week 96, and 81% were responders at week 192. ASAS 5/6 response rates were 61% at week 96 and 60% at week 144, and partial remission response rates were 41% at week 96 and 44% at week 192. Placebo patients who switched to etanercept in the OLE showed similar patterns of efficacy maintenance. Conclusions: Etanercept was well tolerated for up to 192 weeks in patients with AS, with no unexpected AEs or SAEs observed. No deaths were reported. Improvements in the signs and symptoms of AS were maintained for up to 192 weeks.

A proposed revision to the ACR20: The hybrid measure of American College of Rheumatology response

Abstract: Objective Although use of the American College of Rheumatology 20% improvement criteria (ACR20) has standardized response measurement in rheumatoid arthritis (RA) trials, the ACR20 has been criticized as less sensitive to change than are continuous measures of response, and its threshold for response (≥20%) is thought to be low. Our goal was to redefine response in RA in a manner that 1) corresponds to a clinical impression of response (clinical validity), 2) maximizes sensitivity to change, and 3) allows for calculation of the ACR20 to continue standardization of reporting. Methods We examined multiple different ways of defining response, including dichotomous definitions (patient improved versus not improved), ordinal definitions (degree of response scored on an ordinal scale), disease activity indexes, continuous definitions, and definitions that were hybrids of continuous and ordinal measures. Candidate definitions included the ACR20, ACR50, ACR70, the Disease Activity Score, the Simplified Disease Activity Index, the ACR-N, the nACR, and the European League Against Rheumatism (EULAR) response. We also tested variations on these approaches. To test clinical validity, we administered a survey involving patients from a previous trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. To determine sensitivity to change, we collected data from 11 large multicenter trials of disease-modifying antirheumatic drugs (DMARDs) in RA comprising 3,665 patients (7 anti–tumor necrosis factor α arms, 4 conventional DMARD arms, 2 biologic arms) and ranked candidate definitions of response according to their average P value across trials in distinguishing active treatment from placebo or combination therapy versus single-drug therapy. Results All 135 tested measures had clinical validity based on survey responses, although dichotomous measures did not capture the range of responses (e.g., the ACR20 did not capture the extra clinical improvement between the ACR20 and the ACR50). In trial analyses, continuous measures had the best sensitivity to change. Among the best scoring measures was a hybrid measure that retained information on the ACR20, ACR50, and ACR70 and combined that with the mean percent improvement in core set measures. When comparing 2 treatments, this hybrid measure had an average P value much lower than that for the ACR20. If a trial needed 200 patients to have 80% power (2-sided α = 0.05) to detect a difference between treatments if it used the ACR20, the same trial would need 108 patients if the hybrid measure were used. Conclusion We suggest use of a new hybrid measure of RA response that maximizes sensitivity to change, correlates well with rheumatologists' impressions of improvement, and preserves the ACR20.

The development of a preliminary ultrasonographic scoring system for features of hand osteoarthritis

Abstract: Objectives: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. Methods: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. Results: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1–3 scale. The reliability exercise demonstrated intra-reader κ values of 0.444–1.0, 0.211–1.0 and 0.087–1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability κ values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. Conclusions: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Complication rates of 127 surgical procedures performed in rheumatic patients receiving tumor necrosis factor alpha blockers.

Abstract: Objective Tumor necrosis factor (TNF) blockers have been reported to increase the risk of infections, thrombosis, and delayed healing. However, there is little data on the risk of complications after surgery in rheumatic patients receiving TNF blockers. The aim of this study was to assess the complication rate after surgery in such patients, to assess the effect of interrupting TNF blocker therapy, and to identify other potential predictors of complications. Methods This was a systematic, retrospective monocenter study of all patients treated with TNF blockers and who underwent surgery. Complications were recorded and complication rates were compared based on the type of surgery and the timing of the discontinuation of TNF blockers before surgery (above 2 or 5 half-lives). The complication rates were compared with those reported in the literature (orthopaedic procedures in RA patients: 7%, abdominal surgery: 13%). Results Between 1997 and 2004, 770 patients were treated with TNF blockers of whom 92 underwent surgery (127 surgical procedures). The most frequent underlying disease was rheumatoid arthritis (77%). Most of the surgical procedures were orthopaedic (85%). The complication rates for orthopaedic procedures and for abdominal procedures were 13% and 43%, respectively. The infection rate after orthopaedic procedures was 6.5%. Interrupting therapy before surgery did not significantly decrease the postoperative complication risk. There were no independent factors predicting complications. Conclusion In daily practice the complication rate after surgery is high in patients treated with TNF blockers. Discontinuing TNF therapy before surgery should be considered, although this study did not clearly demonstrate its role.

Radiological damage in patients with rheumatoid arthritis on sustained remission

Abstract: Objective: To assess the radiological damage progression in patients with recent rheumatoid arthritis in sustained remission. Methods: A cohort of 191 patients with active early ( Results: 57 patients died, were lost to follow-up or had incomplete data; 30 (15.7% of those who completed) patients were in remission at 3 and 5 years. The SHS in these two groups was not significantly different at baseline (p = 0.15), but was lower in the remission group at 5 years (p = 0.0047). The median (IQR) radiographic score increased from 0.5 (0–7) at baseline to 2.5 (0–14) after 5 years for the remission group (p = 0.18) and from 2 (0–7) to 13 (3–29) in the group with active rheumatoid arthritis (p 4.1 points) and 6 (20%) presented new erosions in a previously unaffected joint between the third and the fifth years. Conclusion: Patients with early rheumatoid arthritis in sustained remission did not present statistically significant radiographic degradation at the group level; nevertheless, 16.7% of these patients did present degradation. Absence of progression should be part of the remission definition in rheumatoid arthritis.

Vertebral dimensions as risk factor of vertebral fracture in osteoporotic patients: a systematic literature review

Abstract: This systematic literature review studied the potential association between vertebral fracture risk and vertebral dimensions. Analysis showed that patients with vertebral fractures have smaller non-fractured vertebrae than patients without fractures. Vertebral size is an independent risk factor of vertebral fractures. Biomechanical factors such as vertebral dimensions may be a risk factor for vertebral fractures beside bone mineral density (BMD). The objective of this study was to evaluate potential association of vertebral size and shape with osteoporotic fracture risk through a systematic literature review. Systematic analysis of published reports comparing vertebral dimensions of patients with and without osteoporotic fractures was performed. Data sources were electronic databases. Data extraction included methods, site, reproducibility and results of vertebral measurement, study population characteristics. It was noted if populations were matched or data were adjusted for age, height, weight and BMD. Of 634 reports identified by the literature search, the final review included 13 reports studying 4,428 women and 508 men; median age 64.2 years [range 51.7%–73.0%]. Measurements were performed with computed tomography scan, X-ray, or dual energy X-ray absorptiometry. Vertebral body height, width, depth, area, cross-sectional area (CSA), and volume were 5.5% to 9.5% smaller in fractured group than control group. After adjustment for confounding factors, area, CSA and volume were, respectively, 10.2% [range 7.1%–13.3%], 7.7% [range 1.2%–14.2%] and 9.5% [8.5%–10.5%] smaller in fractured group. Vertebral size should be considered as a potential independent vertebral fracture risk factor.

Validation of a short form of the Western Ontario and McMaster Universities Osteoarthritis Index function subscale in hip and knee osteoarthritis

Abstract: OBJECTIVE: A short version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scale has recently been developed to enhance the applicability of the scale in routine practice and clinical research for patients with hip and knee osteoarthritis. The goal of the present study was to validate this short form. METHODS: We conducted a prospective 4-week cohort study of 1,036 outpatients. Performance on the WOMAC function long form (LF) and short form (SF) was compared. Agreement between responses on the 2 forms was examined according to a Bland-Altman plot. Responsiveness to change (by standardized response mean [SRM]), reproducibility (intraclass correlation coefficient [ICC]), and internal consistency (Cronbach's alpha) were computed for both forms. Construct validity was assessed based on functional impairment as measured on a numerical rating scale. RESULTS: At baseline, 24% of patients who completed the WOMAC LF had missing data for at least 1 item as compared with only 6% of patients who completed the WOMAC SF. The mean WOMAC SF score was greater than the mean WOMAC LF score (mean +/- SD difference -4.3 +/- 4.8 on a 0-100 scale). SRMs were 0.61 and 0.73, ICCs were 0.76 and 0.68, and Cronbach's alphas were 0.93 and 0.85 for the WOMAC LF and SF, respectively. The 2 forms had comparable correlation with functional impairment. CONCLUSION: The WOMAC function short form has a low rate of missing data and is a responsive, reproducible, and valid measure. The mean SF score was 4 points higher than the mean LF score.

Research in hand osteoarthritis: time for reappraisal and demand for new strategies. An opinion paper

Abstract: BACKGROUND: Osteoarthritis of the hands is a prevalent musculoskeletal disease with a considerable effect on patients' lives, but knowledge and research results in the field of hand osteoarthritis are limited. Therefore, the Disease Characteristics in Hand OA (DICHOA) initiative was founded in early 2005 with the aim of addressing key issues and facilitating research into hand osteoarthritis. OBJECTIVE: To review and discuss current knowledge on hand osteoarthritis with regard to aetiopathogenesis, diagnostic criteria, biomarkers and clinical outcome measures. METHODS: Recommendations were made based on a literature review. RESULTS: Outcomes of hand osteoarthritis should be explored, including patient perspective on the separate components of disease activity, damage and functioning. All imaging techniques should be cross-validated for hand osteoarthritis with clinical status, including disease activity, function and performance, biomarkers and long-term outcome. New imaging modalities are available and need scoring systems and validation. The role of biomarkers in hand osteoarthritis has to be defined. CONCLUSION: Future research in hand osteoarthritis is warranted.

Disease activity measures for rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is an inflammatory autoimmune and progressive disease. In patients with RA, persistent disease activity ultimately results in irreversible radiographic damage of the joints with persistent functional loss as a consequence. Disease activity measures assess a disease state at a particular time point. In order to evaluate the course of the disease in daily clinical practice or to judge the efficacy of a treatment in a clinical trial, a measure should also comprise the dimension of time. Composite indices provide a comprehensive view of disease activity and include the Disease Activity Score 28, the American College of Rheumatology criteria and newer indices such as the Clinical Disease Activity Index, the Rheumatoid Arthritis Disease Activity Index, and the Simplified Disease Activity Index. The target of RA treatment is to suppress disease activity as completely as possible, with remission being the ultimate goal. The composite index chosen should, therefore, be applicable to the circumstance in which it will be used, with different requirements in clinical practice versus clinical trials. In addition to the choice of an assessment index, novel disease monitoring strategies have been used to optimize treatment and disease control, as in the TICORA and BeST studies. It is clear that the best benefit for the patient can be obtained by combining the optimal treatment strategy and the most appropriate outcome measure. Low disease activity, intensive monitoring, and rapid adjustments in treatment seem to promise the greatest benefit. Further studies are required to better evaluate the clinical relevance of methods for assessing disease activity in patients with RA.

Effect of a collective educational program for patients with rheumatoid arthritis: a prospective 12-month randomized controlled trial.

Abstract: OBJECTIVE: To evaluate the effect on health and functional status of an 8-week group-education program for rheumatoid arthritis (RA) in addition to usual medical care. METHODS: All consecutive inpatients and outpatients with RA (ACR criteria) were asked to participate in this randomized, prospective, controlled trial. The educational intervention consisted of 8 weekly ambulatory sessions, each lasting 6 hours. Followup was undertaken after 1 year. The primary criterion for judging effectiveness was the Health Assessment Questionnaire (HAQ) score; secondary criteria consisted of coping, medical knowledge, patient global satisfaction, and quality of life scores before the intervention and after 1 year. RESULTS: We asked 1242 inpatients and outpatients to participate in the study: 208 (16.75%) agreed (104 in each group). At baseline, there was no statistically significant difference between the 2 groups. After 1 year, no statistically significant difference was observed between the 2 groups in change in HAQ score: -0.04 +/- 0.46 (education group) vs -0.06 +/- 0.47 (control group) (p = 0.79). Statistically significant differences were found in 3 domains: patient coping (-1.22 +/- 5.55 vs -0.22 +/- 3.81; p = 0.03), knowledge (3.42 +/- 4.73 vs 0.73 +/- 3.78; p

Classification criteria for rheumatic diseases: Why and how?

Abstract: , Johnsonet al report the results of a systematic literature research onthe main psychometric properties of classification criteriafor rheumatic diseases (1). A previous editorial (2), writtenby members of the American College of Rheumatology(ACR) Classification and Response Criteria Subcommitteeof the Committee on Quality Measures, emphasized themain steps to follow when proposing classification and/orresponder criteria, and in their article, Johnson et al giveuseful additional information on this topic.The main scientific societies in rheumatology, such asthe ACR and the European League Against Rheumatism(EULAR), strongly support research in the field of classi-fication or responder criteria and have promoted appropri-ate standing committees for this purpose. Within EULAR,there are 2 committees dealing with criteria: the StandingCommittee of Epidemiology, and the Standing Committeefor International Studies Including Clinical Trials. Withinthe ACR, the Committee on Quality Measures is in chargeof this aspect.The role of the ACR and EULAR in defining criteria is topromote procedures that are useful for optimizing the col-laboration between experts in a rheumatologic field ofinterest (e.g., rheumatoid arthritis, ankylosing spondylitis,gout, osteoarthritis, etc.) and experts in the field of clinicalepidemiology (3). Most experts in a specific field of rheu-matology are not also experts in the field of clinical epi-demiology and, therefore, might not be the appropriatepeople to plan, conduct, and analyze studies in order topropose criteria for rheumatic diseases. Similarly, mostexperts in clinical epidemiology are not also experts inspecific topics of rheumatic disorders. There is a need tocombine their expertise. Therefore, the role of the appro-priate EULAR and ACR committee is to help colleagueswho are experts in a specific field and are planning topropose criteria by providing them with expertise in thefield of clinical epidemiology.Such expertise can be provided by obtaining a criticalreview of applications by the appropriate committee, or byproposing a clinical epidemiologist to be part of the taskforce aimed at proposing criteria. In the latter case, whichis the current EULAR procedure for the elaboration ofrecommendations (3), it is mandatory for each task force topropose both a convener, who is usually the expert in thefield of research, and a clinical epidemiologist, who maybe inexperienced in the specific disease. For example,Bernard Combe and Robert Landewe´ acted as the convenerand clinical epidemiologist, respectively, for the EULARrecommendations for management of early arthritis (4).A basis for recommendations and procedures proposedby the ACR Classification and Response Criteria Subcom-mittee of the Committee on Quality Measures with regardto the elaboration and validation steps of criteria for rheu-matic diseases has been explicitly described in the articleby Johnson et al (1). It should be emphasized that due tothescreeningtechniqueJohnsonetalusedinselectingsetsof criteria to assess, their review is not exhaustive of allexisting sets of criteria, but rather is aimed at raisingawareness of methodologic issues regarding diagnosticand classification criteria. This article is a basis for furtherresearch in the field of criteria (i.e., it can be used as afuture work agenda). We strongly recommend readingtheir Methods section carefully, as we feel that it reflectsthe suggestions of the ACR Quality Measures Committee,which were presented in an earlier editorial in

Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis

Abstract: Background: Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis ( RA). Objective: To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA. Methods: This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20. Results: Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated. Conclusions: This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.

Evaluation of the Patient Acceptable Symptom State in a pooled analysis of two multicentre, randomised, double-blind, placebo-controlled studies evaluating lumiracoxib and celecoxib in patients with osteoarthritis

Abstract: Patient Acceptable Symptom State (PASS) is an absolute threshold proposed for symptomatic variables in osteoarthritis (OA) to determine the point beyond which patients consider themselves well and, as such, are satisfied with treatment. Two large previously reported studies of knee OA have shown that both lumiracoxib and celecoxib were superior to placebo in terms of conventional outcome measures. To assess the clinical relevance of these results from the patient's perspective, the same data pooled from these two studies were analysed with respect to the PASS. In total, 3,235 patients were included in two multicentre, randomised, double-blind studies of identical design. Patients were randomly assigned to receive lumiracoxib 100 mg once daily (n = 811), lumiracoxib 100 mg once daily with an initial dose of lumiracoxib 200 mg once daily for the first 2 weeks (100 mg once daily with initial dose [n = 805]), celecoxib 200 mg once daily (n = 813), or placebo (n = 806) for 13 weeks. Treatments were compared with respect to the PASS criteria (for OA pain, patient's global assessment of disease activity, and the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 [WOMAC™ LK 3.1] Function [difficulty in performing daily activities] subscale score). At week 13, 43.3%, 45.3%, and 42.2% of patients in the lumiracoxib 100 mg once daily, lumiracoxib 100 mg once daily with initial dose, and the celecoxib 200 mg once daily groups, respectively, considered their current states as satisfactory versus 35.5% in the placebo group. Similar results were observed for patient's global assessment of disease activity and WOMAC™ LK 3.1 Function subscale score. This post hoc analysis suggests that the statistical significance of the results observed with lumiracoxib or celecoxib compared with placebo using conventional outcome variables is complemented by clinical relevance to the patient. Trial registration numbers: NCT00366938 and NCT00367315.

How do the EQ-5D, SF-6D and the well-being rating scale compare in patients with ankylosing spondylitis?

Abstract: Purpose: To compare aspects of validity of EuroQol—5 Dimensions (EQ-5D) and Short-Form—6 Dimensions (SF-6D), two indirect utility instruments, and the well-being rating scale (RS) in ankylosing spondylitis (AS). Methods: EQ-5D, SF-6D and RS were available for 254 patients fulfilling modified New York criteria. 134 patients were part of an observational cohort and 120 were part of a randomised controlled trial (RCT). Aspects of validity assessed were truth (agreement and correlation with external health measures) and discrimination (differentiation between health states, repeatability and detection of treatment effect). Results: Median (range) values were 0.69 (−0.08–1.00) for the EQ-5D, 0.65 (0.35–0.95) for the SF-6D and 0.65 (0.14–1.00) for the RS. Agreement (intraclass correlation coefficient) was moderate (0.46–0.55). Instruments correlated equally with disease activity, functioning and quality of life. The SF-6D showed smaller average differences in utility between patients with better and worse disease compared with the EQ-5D and the RS. The smallest detectable difference (SDD) (in the control group of RCT) was 0.36, 0.17 and 0.33 for EQ-5D, SF-6D and RS, respectively. The ability to detect treatment effect (in the intervention trial) showed standardised effect sizes that were moderate for EQ-5D and SF-6D (0.63 and 0.64) and low for the RS (0.23). Conclusion: In patients with AS, EQ-5D, SF-6D and the RS correlate equally well with external measures of health, but have different psychometric properties. The SDD is most favourable for the SF-6D, but it discriminates less well between patients with different disease severities. The RS has a poorer ability to detect treatment effects. It is difficult to recommend one of the instruments.

C-reactive protein predicts tumor necrosis factor-alpha blocker retention rate in axial ankylosing spondylitis.

Abstract: OBJECTIVE: In ankylosing spondylitis (AS), tumor necrosis factor (TNF) blockers are recommended for patients with high symptomatic disease activity. Few data are available about objective signs of inflammation such as increased C-reactive protein (CRP). We assessed the retention rate of TNF blockers in patients with axial AS, according to baseline CRP and other potentially predictive measures. METHODS: A retrospective study of all patients treated with TNF blockers for axial AS. Retention rate was evaluated using a survival-data analysis technique with discontinuation of the drug because of inefficacy (Kaplan-Meier method). Potential factors explaining the retention rates (demographic and clinical indicators and CRP) were evaluated using log-rank tests and a Cox proportional-hazards regression model. RESULTS: For axial AS, 175 patients received TNF blockers (men 78%, mean disease duration 12.4 +/- 9.1 yrs); 100 patients (of 143 with available data) had an increased CRP (> 10 mg/l). An increased CRP at baseline was the only variable explaining the retention rate in the Cox model (p = 0.003, hazard ratio = 3.3, 95% CI 1.5-7.3). CONCLUSION: Interruption for expert opinion of inefficacy was more frequent for patients with low baseline CRP; however, even in these patients retention was high. Increased CRP should not be considered mandatory for proposing TNF blocker treatment in axial AS.

Individualising the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale: incorporating patient priorities for improvement to measure functional impairment in hip or knee osteoarthritis

Abstract: OBJECTIVE: Recommended outcome measures in osteoarthritis are standardised scales identical for each patient. As patient-specific scales are of increasing interest when considering patient priorities in outcome assessment, this study aims to validate individualised forms of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale. PATIENTS AND METHODS: WOMAC function subscale data were prospectively obtained from 1218 outpatients with hip or knee osteoarthritis requiring non-steroidal anti-inflammatory drugs. Patients also rated the importance to remove disability in each activity of the WOMAC function subscale, and selected the five activities they considered the most important to be improved upon. After treatment, patients again completed the WOMAC function subscale. Several individualisation methods were evaluated: methods whereby the score of each item is multiplied by, or added to, its importance, and methods based on the five most important activities (WOMAC top 5). Psychometric properties of individualised scales were compared to those of the WOMAC function subscale. RESULTS: The missing data rate was 11%, 13% and 2% for the WOMAC function, its individualised forms and the WOMAC top 5, respectively. Combining severity and importance of each item did not improve the properties of the scales. The WOMAC top 5 was the most responsive scale (standardised response mean: 0.96 vs 0.80, p<0.001). CONCLUSION: Because of its better responsiveness, ease of use, low missing data rate and ability to highlight patient priorities, the WOMAC top 5 could be an interesting tool in therapeutic evaluation in hip or knee osteoarthritis.

Short-term efficacy of rofecoxib and diclofenac in acute shoulder pain: a placebo-controlled randomized trial.

Abstract: Objectives To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain. Design Randomized controlled trial of 7 days. Setting Rheumatologists and/or general practitioners totaling 47. Participants Acute shoulder pain. Interventions Rofecoxib 50 mg once daily, diclofenac 50 mg three times daily, and placebo. Outcome measures Pain, functional impairment, patient's global assessment of his/her disease activity, and local steroid injection requirement for persistent pain. The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success (improvement in pain intensity and a low pain level sustained to the end of the 7 days of the study; log-rank test). Results There was no difference in the baseline characteristics between the three groups (rofecoxib n = 88, placebo n = 94, and diclofenac n = 89). At day 7, the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo (54%, 56%, and 38% in the diclofenac, rofecoxib, and placebo groups respectively, p = 0.0070 and p = 0.0239 for placebo versus rofecoxib and diclofenac, respectively). During the 7 days of the study, there was a statistically significant difference between placebo and both active arms (rofecoxib and diclofenac) in all the evaluated outcome measures A local steroid injection had to be performed in 33 (35%) and 19 (22%) patients in the placebo and rofecoxib group respectively. Number needed to treat to avoid such rescue therapy was 7 patients (95% confidence interval 5–15). Conclusion This study highlights the methodological aspects of clinical trials, e.g., eligibility criteria and outcome measures, in acute painful conditions. The data also establish that diclofenac and rofecoxib are effective therapies for the management of acute painful shoulder and that they reduce the requirement for local steroid injection. Trial Registration ClinicalTrials.gov NCT00140933

EULAR efforts to define quality of care.

Abstract: EULAR is deeply involved in the field of quality of care of musculoskeletal disorders via numerous initiatives. EULAR has promoted initiatives in the different steps involved in improving/facilitating quality of care (e.g. original studies (basic, translational, clinical research studies), meta-analysis/systematic literature research, elaboration and dissemination of recommendations, ...). Moreover, EULAR is promoting educational programs and is lobbying at the European Community level in order to improve the recognition of musculo-skeletal disorders.