Changes of anti-citrullinated peptide antibodies titers after biologic treatment in patients with rheumatoid arthritis: a systematic literature review and retrospective study.

OBJECTIVES: There is an increasing body of evidence suggesting a direct pathophysiological role of anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA), and immunological remission could be a target for treatment. However, data related to the ability of biologics to reduce ACPA titres are contradictory.We aimed to evaluate the changes in ACPA titres after treatment with different biologics in patients with RA. METHODS: As a first step, a systematic review of the literature available on 3 biologics (TNFi, abatacept and rituximab) and ACPA in patients with RA was performed in Pubmed and Cochrane. As a second step, a retrospective study was performed: all RA patients treated with the 3 above-mentioned biologics were identified. To be included in the analysis, patients had to have at least two titres of ACPA (one before and one after biologic treatment) available. ACPA titres were compared before and after treatment in each of the treatment groups. RESULTS: As a result of the literature review, 24 articles were retained confirming that the data on change in ACPA under biologics is contradictory, particularly for abatacept and TNFi. 144 RA patients (79.3% female, mean age: 56 years) were included in the retrospective analysis: 59 patients had received rituximab, 31 abatacept, 55 TNFi. ACPA titres decreased significantly with rituximab but not with abatacept nor TNFi. Modelling of ACPA titres over follow-up confirmed the significant decrease of ACPA over time rituximab. CONCLUSIONS: In this real-life study, ACPA titres only significantly decreased after treatment with rituximab.

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Glucocorticoid-sparing in patients suffering from rheumatoid arthritis and treated with tocilizumab: the SPARE-1 study.

OBJECTIVES: To describe steroid-sparing in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: To evaluate the proportion of RA patients treated with more than 5 mg of prednisone (or equivalent)/day and starting TCZ who can receive less than 5 mg/day after 12 months without intensification of disease-modifying anti-rheumatic drugs (DMARDs), we conducted a non-interventional, multicentre, prospective study from 2011 to 2013. We included patients with moderate-to-severe RA, >18 years old, starting TCZ and receiving corticosteroids (GCs) at a dose greater than 5 mg/day of prednisone for at least 3 months. RESULTS: Amongst the 307 analysed patients (78% women, median RA duration: 8 years, mean DAS28-ESR: 5.1±1.3), 40% (95%CI=[35-46]) reached the targeted daily prednisone dose at M12, without conventional synthetic (cs)DMARD intensification. Predictive factors were RA duration of 5 years or less (OR=2.60, p=0.01), daily prednisone dose of 7.5 mg or less (OR=2.12, p=0.03), and low ESR value before the first TCZ infusion (OR=0.86, p=0.047). The proportion of patients with no more GCs increased up to 20% at M12. Disease activity improved over the 1-year period (DAS28-ESR LDA and remission in 41% and 33% of patients at M12, respectively). Amongst the 314 patients analysed for safety, at least one AE and at least one SAE were reported in 211 patients (67%) and in 48 patients (15%), respectively. No unexplained safety signal arose with TCZ. CONCLUSIONS: A biological DMARD as TCZ allows reducing both GCs dose and disease activity in RA patients. Nevertheless, corticosteroid spare in real life is probably lower.

Concordance and agreement between different activity scores in polymyalgia rheumatica.

OBJECTIVE: The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs. METHOD: Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots. RESULTS: A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time. CONCLUSION: The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used. TRIAL REGISTRATION NUMBER: NTC02908217.

Onset of action of etanercept in rheumatoid arthritis based on patient-reported outcomes.

BACKGROUND: Onset of action is considered to be a key characteristic of the treatment of rheumatoid arthritis. The efficacy of TNF blockers is usually evaluated after 2 to 4 weeks of therapy. EULAR-RAID is a valid patient-reported outcome composite index. OBJECTIVES: To evaluate the onset of action of etanercept in rheumatoid arthritis patients according to the EULAR-RAID score. METHODS: An open-label, single-arm (etanercept 50 mg/week), 12-week study was carried out in patients with active rheumatoid arthritis. Patients were asked to fill in the RAID score questionnaire each day for the first 14 days of the study and at the 4-week and 12-week visits. Onset of action was evaluated by considering: a) changes over time of the EULAR-RAID score; b) the percentage of patients achieving an 'acceptable' condition according to the EULAR-RAID score (e.g. a score ≤3.00). RESULTS: Of the 120 screened patients, 108 (female: 75%), age 54±13 years, disease duration 8±7 years) were enrolled. At baseline, patients had active rheumatoid arthritis (DAS: 5.4±0.8; CRP: 18.±30mg/l). Eleven patients dropped out of the study. A statistically significant decrease in the EULAR-RAID score was observed by day 1 of therapy. Kaplan-Meier estimates of the proportion of patients achieving an acceptable RAID score were 29.8 [% 95% C.I. 23.8-X42.6], 50 % [95% C.I. 41-60.9], 51.9% [95% C.I. 43.8-63.7], 56% [95% C.I. 49.5-69.1, after 1, 2, 4 and 12 weeks of therapy respectively. The median time to achieve an acceptable EULAR-RAID score was 14.5 days. CONCLUSIONS: This open-label study suggests that patients can perceive a clinically relevant improvement by the first week of etanercept therapy.

Comparison of Biological Agent Monotherapy and Associations Including Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis: Literature Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: Update the available evidence comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (CsDMARDs) to bDMARDs in monotherapy in patients with rheumatoid arthritis. METHODS: Research was limited to randomized controlled trials. Major outcome: ACR 20 response criteria at 24 weeks. SECONDARY OUTCOMES: clinical and radiographic criteria at week 24, 52 and 104. RESULTS: 23 trials (6358 patients), including seven bDMARDs and one other molecule: Anbainuo (anti-TNF-R). No study satisfied our search criteria for anakinra, certolizumab and infliximab. Compared to bDMARD monotherapy, combination therapy gives a better ACR 20 at 24 weeks (RR: 0.88 (0.84-0.94)) in fixed and random effect models, and this result is sustained at 52 and 104 weeks. The results were mostly similar for all other outcomes without increasing the risk of adverse effects. CONCLUSION: This meta-analysis confirms the superiority of combination therapy over monotherapy in rheumatoid arthritis, in accordance to the usual guidelines.

Comparison of general practitioners and rheumatologists' prescription patterns for patients with knee osteoarthritis.

BACKGROUND: To compare the prescription modalities of general practitioners (GPs) and rheumatologists (RHs) for symptomatic knee osteoarthritis (OA) and to determine correlates with prescription of low-dose NSAIDs. METHODS: This observational, prospective, national survey was carried out among a national representative sample of GPs (n = 808) and RHs (n = 134). Each physician completed a medical questionnaire for the 2 most recent patients fulfilling the ACR criteria for knee OA. RESULTS: GPs and RHs included 1,570 and 251 patients, respectively. Mean pain level of the knee (on a VAS, 0-100 mm) was greater for GP patients than for RH patients (49.8 ± 16.3 vs. 46.2 ± 17.1 mm, respectively; p < 0.01). As compared with patients of RHs, those of GPs more frequently had another joint affected by OA: 71.2% vs. 63.7% (p < 0.0001) and more often had hypertension and diabetes mellitus (p < 0.05). As compared with RHs, GPs more frequently prescribed low-dose NSAIDs (p < 0.0001), oral NSAIDs (p < 0.05), and topical NSAIDs (p < 0.0001) but less frequently symptomatic slow-acting drugs for OA (p < 0.01). Moreover, GPs more frequently recommended rehabilitation (p < 0.01) and loss of weight (p < 0.0001). Logistic regression analysis revealed an association of low-dose NSAIDs prescription and prescription by GPs, prescription of topical NSAIDs, no prescription of oral NSAIDs or coxibs and no intra-articular injection of steroids. CONCLUSIONS: This study identified speciality-related variability in some aspects of the management of knee OA. The clinical profile of patients with knee OA differed between GPs and RHs.

Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Moderate to Severe Active Rheumatoid Arthritis: TANDEM Study.

INTRODUCTION: Drug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: This non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan-Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5). RESULTS: At inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%-69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age. CONCLUSIONS: This real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient's profile (age, BMI), methotrexate doses, and TCZ-SC use. TRIAL REGISTRATION: NCT02608112.

Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. METHODS: Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. RESULTS: One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. CONCLUSIONS: Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. TRIAL REGISTRATION: The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).

Two-year abatacept retention rate in clinical practice in the French ACTION cohort.

OBJECTIVES: Abatacept retention rates were evaluated in the French cohort in the prospective ACTION study (2010-2013), which included patients with moderate-to-severe rheumatoid arthritis managed in everyday clinical practice and started on intravenous abatacept therapy. METHODS: Two-year abatacept retention rates were evaluated in 455 patients classified according to treatment line, body mass index (BMI), and status for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). RESULTS: After 2 years, the overall abatacept retention rate was 44%. The retention rate was non-significantly higher in the patients with vs. without a history of unresponsiveness to at least one biologic (48.1% vs. 41.8%, respectively). No significant retention rate differences were found across BMI categories (444 patients; <25, 45.5%; ≥25 to <30, 48.9%; and ≥30, 36.6%). Neither were any significant differences demonstrated according to RF and ACPA status (RF+ and ACPA+, 45.7%; RF+ or ACPA+, 43.8%; and FR- and ACPA-, 39.1%). CONCLUSION: The 44% 2-year retention rate in the French ACTION cohort supports the usefulness of abatacept therapy. In this study, retention was not associated with treatment line, BMI, or antibody status.

Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations.

UNLABELLED: Mutation screening of the SQSTM1 gene in 94 French patients with PDB revealed two novel point-mutations (A381V and L413F) and two new compound heterozygous genotypes (P392L/A381V and P392L/A390X). Functional analysis showed an increased level of SQSTM1/p62 protein in PDB patients and truncated forms of the protein encoded by the A390X allele. Clinical data indicate that PDB patients with SQSTM1 mutation are younger at PDB diagnosis and have more extensive bone lesions. INTRODUCTION: Paget's disease of bone (PDB) is a common chronic disease of the skeleton, with a strong genetic component. A recurrent mutation (P392L) was first identified on chromosome 5, in the Sequestosome 1 (SQSTM1) gene. Several other mutations of the SQSTM1 gene have been described in PDB patients, affecting the ubiquitin-associated domain (UBA) of the SQSTM1/p62 protein. The objectives of this study were to evaluate the frequency of the SQSTM1 mutations in French PBD patients, to study the expression of the SQSTM1/p62 protein, and to search for genotype-phenotype correlations. MATERIALS AND METHODS: Blood was obtained from 94 unrelated French PDB patients and 100 controls for mutation screening of exons 7 and 8, encoding for the UBA domain of SQSTM1. Epstein-Barr virus (EBV)-immortalized B-cell lymphocytes were established from 13 patients, giving access to functional analysis of the gene and the SQSTM1/p62 expressions using real-time PCR and Western blot. RESULTS: Mutations of the SQSTM1 gene were identified in 12 of the 94 PDB patients (13%). Eight patients carried P392L. Two novel missense mutations were identified: L413F and A381V. This A381V mutation and A390X were found in distinct patients already carriers of P392L. The SQSTM1/p62 protein expression in PDB patients increased when zero, one, or two mutations were present, and SQSTM1 truncated forms were associated with the A390X mutation. The mean age of PDB diagnosis was younger in patients with the SQSTM1 mutation. PDB was more extensive in patients who carried a SQSTM1 mutation. CONCLUSIONS: Mutations of SQSTM1 are present in the French population. PDB patients with and without the SQSTM1 mutation have an increased level of SQSTM1/p62, caused by overproduction of the protein, probably involved in the pathophysiology of PDB. The presence of the SQSTM1 mutation may be a worsening factor for PDB.

Characterisation of patients with postmenopausal osteoporosis in French primary healthcare.

BACKGROUND: The public health burden of osteoporosis is high, principally because of increased risk of fractures and associated morbidity, handicap and mortality. Osteoporotic fracture prevention is therefore an important public health goal. General practitioners (GPs) play a key role in the management of osteoporosis, both in ensuring timely diagnosis and in providing treatment. Little information is available on standards of care for postmenopausal women with osteoporosis in general practice. OBJECTIVES: The primary objective of this study was to describe risk factors and treatment in postmenopausal women with osteoporosis. Secondary objectives were to evaluate treatment compliance and to assess the impact of osteoporosis on quality of life. METHODS: This observational, cross-sectional, pharmacoepidemiological study was performed in a primary-care setting in France. A random sample of GPs recruited postmenopausal women with a diagnosis of osteoporosis who had been followed by the investigator for at least 2 years. At inclusion, investigators completed a questionnaire providing information on patient age, osteoporosis duration, risk factors and treatment history. The first three patients recruited by each investigator completed a questionnaire providing information on sociodemographic features, osteoporosis treatments and quality of life. Treatment compliance was quantified using the Test d'Evaluation de l'Observance and quality of life evaluated using the 12-item Short Form Health Survey (SF-12). RESULTS: Overall, 389 physicians included 3,097 patients, of whom 1,053 completed the patient questionnaire. Risk factors for osteoporotic fracture were identified in 2,148 patients (69.4%), most frequently personal or maternal antecedents of osteoporotic fracture and a low body mass index. Of these, 946 (44.0%) presented more than one risk factor. At the time of diagnosis, 629 patients (59.7%) presented fractures, which involved the vertebrae in 51.7% of cases, the wrist in 40.5% and the hip in 5.4%. Older patients were more likely to have fractures at the time of diagnosis and to have multiple fractures. After diagnosis, at least one new fracture occurred in 201 patients (19.2%). Multivariate logistic regression analysis identified age >70 years, diagnosis at least 10 years previously, diagnosis based on the presence of a fracture, biochemical and haematological evaluation at the time of diagnosis, and a change in osteoporosis treatment in the previous 2 years as being significantly associated with incident fracture risk. At inclusion, 1,019 patients (97.4%) were receiving treatment for osteoporosis, most frequently weekly bisphosphonates (71.6% of treatments). Most patients (81.0%) had been treated for at least 1 year. Treatment compliance was high in 61% of patients and low in <5%. Patient variables associated with high compliance were being retired, prescription of bisphosphonates and, among the bisphosphonate users, prescription of weekly formulations. SF-12 quality-of-life scores were low, ranging from 38.6 (energy/vitality) to 65.1 (social functioning) out of a possible maximum score of 100. Baseline variables associated with SF-12 physical component summary scores included age, height loss since menopause, diagnosis following a fracture, fracture incidence since diagnosis, time since diagnosis and treatment with bisphosphonates. CONCLUSIONS: In this study of postmenopausal osteoporosis in the French primary healthcare setting, many women with osteoporosis were diagnosed following a fracture. Although most were treated with bone-consolidating drugs, compliance was suboptimal in a significant minority. Osteoporotic fracture was associated with reduced quality of life.

Osteoarthritis of the knee and hip and activity: a systematic international review and synthesis (OASIS).

UNLABELLED: The goal of this study was to determine which activities in four domains, daily life, exercises, sports and occupational activities, should be recommended, in favor or against, for the patient suffering from knee or hip OA. METHODS: Scientific literature was searched in Medline, Embase and Cochrane databases for articles in French or English, reporting original data. The articles were evaluated with standardized epidemiological criteria. Seventy-two articles were retained. Recommendations were graded according to the level of scientific evidence (A high, B moderate, C clinical consensus) and were formulated for primary care. CONCLUSIONS AND RECOMMENDATIONS: For activity of daily life (ADL), the OASIS group states with a moderate level of scientific evidence, that ADL are a risk factor for knee OA and that risk increases with intensity and duration of activity. The group concludes that healthy subjects as well as OA patients in general can pursue a high level of physical activity, provided the activity is not painful and does not predispose to trauma (grade B). Radiographic or clinical OA is not a contraindication to promoting activity in patients who have a sedentary lifestyle (grade C). For exercises and other structured activities pursued with a goal of health improvement, the group states with a high level of scientific evidence that they have a favourable effect on pain and function in the sedentary knee OA patient. The OASIS group recommends the practice of exercises and other structured activities for the sedentary patient with knee OA (grade A). Static exercises are not favored over dynamic exercises, availability, preference and tolerance being the criteria for the choice of an exercise (grade A). As results deteriorate when exercises are stopped, they should be performed at a frequency of between one and three times per week (grade B). Professional assistance can be useful in improving initial compliance and perseverance (grade B). There is no scientific argument to support halting exercise in case of an OA flare-up (grade C). For sports and recreational activity, the group states with a high degree of scientific evidence, that these activities are a risk factor for knee and hip OA and that the risk correlates with intensity and duration of exposure. The group also states, with a high degree of scientific evidence, that the risk of OA associated with sport is lesser than that associated with a history of trauma and overweight. No firm conclusion could be drawn about the possible protective role of sports such as cycling, swimming or golf. The OASIS group recommends that athletes should be informed that joint trauma is a greater risk factor than the practice of sport (Grade A). The high level athlete should be informed that the risk of OA is associated with the duration and intensity of exposure (Grade B). The OA patient can continue to engage regularly in recreational sports as long as the activity does not cause pain (Grade C). The OA patient who practices a sport at risk for joint trauma should be encouraged to change sport (Grade C). For occupational activity, the OASIS group states with a high level of scientific evidence that there is a relationship between occupational activity and OA of the knee and hip. The precise nature of biomechanical stresses leading to OA remains unclear but factors such as high loads on the joint, unnatural body position, heavy lifting, climbing and jumping may contribute to knee and hip OA. The group recommends that taking an occupational history should always be part of managing the OA patient (Grade B). In the knee or hip OA patient, work-related activity that produces or maintains pain should be avoided (Grade B). Physicians should be alerted by the early knee and hip signs and symptoms in workers exposed to stresses that are known or supposed to favour knee or hip OA (Grade C).

Impact of osteoarthritis: results of a nationwide survey of 10,000 patients consulting for OA.

UNLABELLED: The clinical burden of osteoarthritis (OA) is difficult to assess because of the substantial variability between patients. OBJECTIVE: Evaluate the human consequences of OA in patients. METHODS: In 2000, a nationwide survey was conducted among a sample of more than 5000 physicians (90.3% general practitioners and 9.7% rheumatologists), representative of French physicians. Each recruited the first two patients consulting for hip, knee, or hand OA after the survey began. The functional limitation rates were compared with those for age- and sex-matched controls obtained from the 1999 population-based national survey on disability (HID survey). RESULTS: Clinical and demographic information was obtained for 10,412 OA patients (mean-age 66.2 years, sex ratio F:M 1.96). The OA diagnosis was based on both clinical and radiographic findings for 84.5%. More than 80% of all patients reported limitations in their activities of daily living, either for basic tasks, leisure activities, or work. OA patients were substantially more limited than controls: the standardised limitation rate ratios (SLRR) were 6.0 (95% confidence interval: 5.9:6.1) for mobility outside the home, 2.1 (2.0:2.1) for house cleaning, 1.6 (1.5:1.8) for dressing oneself, and 1.6 (1.5:1.8) for sports. Of the 17.6% of OA patients and 17.5% of the controls still working, 64.4% and 14.3%, respectively, were limited in their job duties, for a SLRR of 4.5 (4.3:4.7). CONCLUSION: This study shows that OA-related disability has a significant impact on the retired as well as on those still involved in the labour market.

Early effect of hyaluronic acid intra-articular injections on serum and urine biomarkers in patients with knee osteoarthritis: An open-label observational prospective study.

The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty-one patients with unilateral symptomatic K-OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D-15 patients were examined and X-rays performed, to exclude patients with bilateral K-OA, or those with more than three symptomatic OA joints. From 15 days (D-15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D-15, D1, D30, and D90. S-C2C, S-Cartilage oligomeric matrix protein, S-HA, S-CS 846 epitope, S-type II collagen propeptide, and U-type II collagen C telopeptide (U-CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty-five patients were analyzed. Between D-15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U-CTX II/creat (p = 0.006). Between D1 and D90: U-CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U-CTX II/creat variation. U-CTX II and S-HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U-CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation.

The influence of the definition of patient global assessment in assessment of disease activity according to the Disease Activity Score (DAS28) in rheumatoid arthritis.

OBJECTIVE: Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity. METHODS: We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy. RESULTS: The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar. CONCLUSION: The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.