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.

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.

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.

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.

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.

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.

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.

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.

Management recommendations for knee osteoarthritis: how usable are they?

OBJECTIVES: Despite the availability of practice guidelines for the management of knee osteoarthritis, inadequacies in practices of clinicians and patients have been found, leading to suboptimal outcomes. Literature has shown that simply disseminating management recommendations does not lead to adherence. Research suggests that barriers to use should be identified and addressed to improve adherence. The objective of this study was to identify barriers to use of conservative management recommendations for knee osteoarthritis by patients, general practitioners and physiotherapists. METHODS: Following systematic reviews of evidence and guidelines, 12 key management recommendations were elaborated on four themes: medication, exercise, self-management and occupation. Focus groups were separately done with patients with knee osteoarthritis, general practitioners and physiotherapists to assess barriers to the use of recommendations. RESULTS: Patients and general practitioners appeared generally fatalistic with regards to knee osteoarthritis, with physiotherapists being more positive regarding long-term improvement of knee osteoarthritis. For medication, discrepancies were found between recommendations and views of clinicians. Both patients and general practitioners appeared ambivalent towards exercise and activity, recognizing its usefulness but identifying it at the same time as a cause of knee osteoarthritis. Patients and general practitioners appeared to consider weight loss particularly difficult. DISCUSSION/CONCLUSIONS: Barriers specific to each knee osteoarthritis management recommendation and stakeholder group were identified. Recommendations to address these barriers were elaborated. Results of this study can be used to develop implementation strategies to overcome identified barriers, with the goal of facilitating the use of guideline recommendations and improving outcomes.

Transcriptome analysis describing new immunity and defense genes in peripheral blood mononuclear cells of rheumatoid arthritis patients.

BACKGROUND: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs) from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR<5%). Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO) in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated) between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. CONCLUSIONS/SIGNIFICANCE: Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions.

Validation of the KOFUS (Knee Osteoarthritis Flare-Ups Score).

OBJECTIVE: To develop a diagnostic score for knee osteoarthritis flare-ups and to evaluate its sensitivity and specificity. METHODS: We used two epidemiological databases built using the same methodology. One database was from a general-practice study and served to develop the score, whereas the other was from a rheumatology study and served to validate the score. Physicians determined the flare-up status of each patient. The rheumatologist diagnosis was the reference standard. Logistic regression was performed to identify factors significantly associated with having a flare-up. RESULTS: Of the 6085 patients in the general-practice database, 52.3% had a knee osteoarthritis flare-up. The score was built by assigning points to features that were present, with a weighting system based on the odds ratio of each feature for having a flare-up (0, feature absent; 1, morning stiffness for longer than 20 min; 2, pain causing nocturnal awakenings and knee effusion; 3, limping, joint swelling, and increased warmth over the knee). The score could range from 0 to 14. The receiver-operating characteristic curve showed that 7 was the best cutoff for diagnosing a flare-up. In the rheumatologist database, the numbers of patients having a flare-up were 274 (46.4%) based on the score and 270 (45.7%) based on the rheumatologist diagnosis. Sensitivity of the score was 87.0%, specificity 87.9%, positive predictive value 85.8%, and negative predictive value 89.0%. The Youden index was 0.75. CONCLUSION: A score equal to or greater than 7 points correlated well with a rheumatologist diagnosis of flare-up. Our score may constitute a valid objective criterion for standardizing the diagnosis of knee osteoarthritis flare-up, most notably when screening patients for inclusion in therapeutic trials.

Genetic and expression analysis of CASP7 gene in a European Caucasian population with rheumatoid arthritis.

OBJECTIVE: To study the possible role of the caspase 7 (CASP7) gene in susceptibility to rheumatoid arthritis (RA) in a European Caucasian population. METHODS: CASP7 rs2227309 single nucleotide polymorphism (SNP) was genotyped in 197 French RA trio families and in 252 European RA families available for replication using Taqman allelic discrimination assay. Relative quantification of caspase 7 isoforms alpha and beta mRNA expression was performed from whole blood in 25 unrelated patients with RA and in 15 healthy controls by real-time quantitative reverse transcription-polymerase chain reaction. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies, the transmission disequilibrium test, and the genotype relative risk. RESULTS: We observed, in the first sample, a significant association of rs2227309-AA genotype with RA [p=0.03, odds ratio (OR) 2.11 (95% CI 1.0-4.6)]. The second sample did not show any significant association of the AA genotype with RA [p=0.6, OR 0.87 (95% CI 0.4-1.8)]. When the 2 samples were combined, no significant association of the AA genotype [p=0.3, OR 1.32 (95% CI 0.8-2.2)] was observed. CASP7 isoforms alpha and beta mRNA were expressed in patients with RA at lower level than in healthy controls (-89%, p=0.003 and -47%, p=0.01; respectively). CONCLUSION: CASP7 rs2227309 SNP was not associated with RA in a European Caucasian population. Nevertheless, CASP7 isoforms alpha and beta could have an involvement in the apoptosis process in RA.