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Objective To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. Methods We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer’s solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. Results Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months’ follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of −9.2 [12.2] in the AD-SVF group vs −7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. Conclusion This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

ContextPrimary Sjögren’s syndrome (pSS) is a complex heterogeneous autoimmune disease (AID) which can mimic rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Our exploratory study investigated serum biomarkers that may discriminate pSS from RA and SLE.MethodsSerum concentrations of 63 biomarkers involved in immune cell trafficking, inflammatory response, cellular movement, and cell-to-cell signaling were measured in AID patients, included prospectively into the study at the Montpellier University Hospital. A multivariate analysis by multiple logistic regression was performed, and discriminative power assessed using logistic regression adjusted on significant demographic factors.ResultsAmong the 95 patients enrolled, 42 suffered from pSS, 28 from RA, and 25 from SLE. Statistical analysis showed that concentrations of BDNF (OR = 0.493 with 95% CI [0.273–0.891]; p = 0.0193) and I-TAC/CXCL11 (OR = 1.344 with 95% CI [1.027–1.76]; p = 0.0314) can significantly discriminate pSS from RA. Similarly, greater concentrations of sCD163 (OR = 0.803 with 95% CI [0.649–0.994]; p = 0.0436), Fractalkine/CX3CL1 (OR = 0.534 with 95% CI [0.287–0. 991]; p = 0.0466), MCP-1/CCL2 (OR = 0.839 with 95% CI [0.732–0.962]; p = 0.0121), and TNFa (OR = 0.479 with 95% CI [0.247–0.928]; p = 0.0292) were associated with SLE diagnosis compared to pSS. In addition, the combination of low concentrations of BDNF and Fractalkine/CX3CL1 was highly specific for pSS (specificity 96.2%; positive predictive value 80%) compared to RA and SLE, as well as the combination of high concentrations of I-TAC/CXCL11 and low concentrations of sCD163 (specificity 98.1%; positive predictive value 75%).ConclusionOur study highlights biomarkers potentially involved in pSS, RA, and SLE pathophysiology that could be useful for developing a pSS-specific diagnostic tool.

International audience; Cardiac toxicity can be induced by hydroxychloroquine, especially when used in combination with azithromycin. Interest in hydroxychloroquine and azithromycin as potential therapies for COVID-19 has renewed concerns about the possible cardiovascular risk these drugs present to patients with rheumatoid arthritis.

ObjectiveTo evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis.MethodsThis was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0–100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients’ and physicians’ global assessment and function scores.ResultsOf 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was −7.9 (SD 19.4) and −9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group.ConclusionTocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

Objectives In RA, telemedicine may allow tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician’s interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA. Methods A six-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new DMARD therapy. Two groups were established: ‘connected monitoring’ and ‘conventional monitoring’. The primary outcome was the number of physical visits between baseline and six months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional and health status scores (Short-Form 12). Results Of the 94 randomized patients, 89 completed study: 44 in the ‘conventional monitoring’ arm and 45 in the ‘connected monitoring’ arm. The total number of physical visits between required baseline and six-month visits was significantly lower in the ‘connected monitoring’ group [0.42 (0.58) vs 1.93 (0.55); P Conclusion Our results suggest that connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03005925.

Background Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the effectiveness of long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. Methods We conducted an exploratory, prospective, single-center, open-label study, on RA patients with sustained remission of at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was extended to 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. Results Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one showing adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p p Conclusions A progressive tapering of TCZ infusions may be possible for many patients. However, larger studies, including more patients, are needed to confirm this therapeutic option. Trial registration NCT02909998. Date of registration: October 2008.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase, polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (&gt, 30 vs. &le, 30 years, HR 4.71, 95%CI [2.40&ndash, 9.27], p &lt, 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

International audience

International audience; INTRODUCTION: Chloroquine and hydroxychloroquine are widely used in the long-term treatment of connective tissue disease and usually considered safe. However, chloroquine- or hydroxychloroquine-related cardiac disorder is a rare but severe adverse event, which can lead to death. This systematic review investigates cardiac complications attributed to chloroquine and hydroxychloroquine. METHODS: PubMED, EMBASE, and Cochrane database searches were conducted using keywords derived from MeSH terms. Reports published prior to 31 July, 2017 were eligible for inclusion, without restriction to study design. Searches were also conducted on reference lists of included studies. RESULTS: Eighty-six articles were identified, reporting individual cases or short series, providing information on 127 patients (65.4% female). A majority of patients were treated with chloroquine (58.3%), with the remaining treated with hydroxychloroquine (39.4%), or both in succession. Most patients had been treated for a long time (median 7~years, minimum 3~days; maximum 35~years) and with a high cumulative dose (median 1235~g for hydroxychloroquine and 803~g for chloroquine). Conduction disorders were the main side effect reported, affecting 85% of patients. Other non-specific adverse cardiac events included ventricular hypertrophy (22%), hypokinesia (9.4%), heart failure (26.8%), pulmonary arterial hypertension (3.9%), and valvular dysfunction (7.1%). For 78 patients reported to have been withdrawn from treatment, some recovered normal heart function (44.9%), while for others progression was unfavorable, resulting in irreversible damage (12.9%) or death (30.8%). LIMITATIONS: The risk of cardiac complications attributed to chloroquine/hydroxychloroquine was not quantified because of the lack of randomized controlled trials and observational studies investigating the association. CONCLUSIONS: Clinicians should be warned that chloroquine- or hydroxychloroquine-related cardiac manifestations, even conduction disorders without repercussion, may be initial manifestations of toxicity, and are potentially irreversible. Therefore, treatment withdrawal is required when cardiac manifestations are present.

Objectives Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. Methods SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. Results No associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P = 0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P Conclusion TRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

Objectives Biologic disease-modifying antirheumatic drugs (bDMARDs) are prescribed sequentially in the treatment of rheumatoid arthritis (RA). Healthcare decision makers continue to debate their use, mainly because of their high costs. Our aim was to perform an economic evaluation for France of bDMARD sequences for treatment of moderate-to-severe RA after inadequate response or intolerance to conventional DMARDs (eg, methotrexate). Methods A discretely integrated condition event simulation was developed to track the course of patients from first bDMARD through switches to further lines in a sequence. The model included 11 events, 91 conditions, and 21 controlling equations. Inputs were obtained from a meta-analysis of clinical trials, a French registry, national drug lists, and databases. Survival, time with minimal activity, quality-adjusted life-years (QALYs), and total costs were output. Structural and probabilistic sensitivity analyses were conducted. Results Sequences starting with etanercept biosimilars (ETB) cost less, with ETB–abatacept–infliximab the least expensive: the mean lifetime discounted total cost was €116 912 per patient, with a mean of 11.166 QALYs. Most other strategies were dominated or led to small QALY gains (0.0008-0.0329). Only ETB–tocilizumab–abatacept made it onto the efficiency frontier, but at €955 778 per QALY gained. These results were confirmed in several scenarios and uncertainty analyses. Conclusion Given minor differences in QALYs gained between bDMARD sequences with large cost differences, starting with biosimilars was more efficient than starting with branded products. Our model and findings should provide French and other decision makers with useful tools to address the challenges of comparing sequences of treatments for RA.

Background TMJ is involved in about 50% of JIA cases, often bilateral and asymptomatic in up to 71% of cases1. Adult patients with JIA have been shown to have, compared to healthy individuals, higher rate of dysfunction and anatomical abnormalities2. Clinical examination has been shown to have high specificity but low sensitivity in revealing TMJ inflammation3. To date MRI is the gold standard to assess TMJ involvement 4 Objectives To investigate the prevalence of TMJ involvement in young adults with JIA and young adults with non-JIA inflammatory rheumatisms. Methods Patients were recruited prospectively in 2 clinical centers. Inclusion criteria were: patients Results 19 patients were included in the JIA group and 8 patients in the non-JIA group. Patients’ demographic and disease characteristics were reported in Table 1. MRI results are collected in Table 2. There are no statistically significant differences between groups for the presence of inflammation on MRI, while damage (in particular, disk abnormalities) is more likely in JIA rather than non-JIA patients (p= 0.02). Joint effusion is more likely to be mild rather than moderate/severe in JIA patients (p = 0.04). Conclusion It was found that it is more likely to find damage on MRI in patients of both groups rather than inflammation. Both groups show the same frequency of TMJ involvement, suggesting that TMJ involvement must be sought by the adult rheumatologist as it not only affects JIA patients, but also those with adult-onset inflammatory arthropathies. References [1] Billiau AD, et al. J Rheumatol. 2007 Sep;34(9):1925–33 [2] Arvidsson LZ, et al. Radiology 2010 Jul;256(1):191–200 [3] Koos B, et al. J Rheumatol. 2014 Sep;41(9):1871–7 [4] Hemke R, et al. Eur Radiol. 2014 Feb;24(2):327–34. Disclosure of Interests None declared

Background TMJ is involved in about 50% of JIA cases, often bilateral and asymptomatic in up to 71% of cases1, leading to higher rate of dysfunction and anatomical abnormalities (as retrognathia, facial asymmetry, limited mouth opening, pain)2. To date MRI is the gold standard to study both TMJ inflammation and damage3 but US is a widely used diagnostic imaging tool in rheumatic patients and may be a cheaper and more accessible alternative. Objectives To investigate the prevalence of TMJ involvement in young adults with JIA and young adults with non-JIA inflammatory rheumatisms, comparing MRI with US. Methods Patients were recruited prospectively in 2 clinical centers. Inclusion criteria were: patients Results 11 patients were included in the JIA group and 7 patients in the non-JIA group. Patients’ and TMJs involvement characteristics were reported in Table 1. Conclusion The concordance between MRI and ultrasound is not optimal, and existing TMJ US protocols are based on children. Further studies are needed to develop a suitable US protocol to detect TMJ involvement in adult patients as a screening tool. References [1] Billiau AD, et al. J Rheumatol. 2007Sep;34(9):1925–33. [2] Arvidsson LZ, et al. Radiology2010Jul;256(1):191–200. [3] Hemke R, et al. Eur Radiol. 2014Feb;24(2):327–34. Disclosure of Interests None declared

Background: Today the objective for efficient Rheumatoid Arthritis (RA) therapy is not restricted to reduced synovial inflammation but to induce immunological and clinicaly lasting remission. Despite improvement in therapy of RA, anti-TNF alpha or anti-IL-6 (Tocilizumab) biologicals provide less than 20% of clinical remission. Interestingly, the complete remission can last up to 12 months in about 40% of these patients despite discontinuation of the above biologicals. In order to set up optimized strategy to obtain persistent clinical remission, new predictive markers of complete remission are needed. Objectives: By using Firalis’ BIOPRED panel, an innovative targeted gene sequencing panel of 2155 mRNA targets associated with immune-inflammatory pathways, we identified candidate biomarkers that have the potential to stratify patients for personalized therapy. Methods: Paxgene RNA samples obtained from 18 RA patients treated with Etanercept (n=11) and Tocilizumab (n=7) who had achieved remission (DAS28 Results: In total, 37 mRNA targets are found to be significantly up- or down-regulated in Etanercept groups as compared to Tocilizumab group (p-value 2 (p-value Conclusion: Our preliminary analysis shows that a panel of candidate predictive markers for biological specific (Etanercept) remission has the potential to stratify patients for personalized therapy in RA patients. Longitudinal studies are required with RA patients treated with all biologicals to validate this signature and explore further dimensions. Disclosure of Interests: None declared

International audience; Background Nearly 1% of the population is currently treated with long-term corticosteroid therapy. When corticosteroids are introduced, information concerning potential adverse effects and recommendations for lifestyle changes aimed at preventing such effects is provided to patients. However, studies have shown patients often do not fully comprehend the information provided and have difficulty implementing the recommended dietary and physical activity advice. In this study, we aim to highlight the difficulties encountered by patients in comprehending and implementing recommendations in the context of long-term corticosteroid use. Such information can be used to better optimize care, particularly concerning adherence to the treatment, the diet, and thus improve the quality of life of patients. Methods We recruited adult patients under long-term corticosteroid (≥ 3 months, ≥ 5 mg/day) treatment from both general medicine and rheumatology practices. We performed a qualitative analysis based on semi-structured interviews of these patients. Transcripts of these interviews were then compiled and analysed using a thematic approach. Results Sixteen patients were included. Analysis of the interviews revealed that patients’ hope for effective corticosteroid treatment was counterbalanced by concerns over potential adverse effects. In some patients, the need to respect a strict and imposed diet induced psychological distress, potentially leading to eating disorders or fear of social exclusion. Furthermore, patient ambivalence toward the therapeutic education was highlighted, as well as the notion of filtering information, conscious or unconscious, as revealed by their lack of recall. The relationship with the physician also affected the treatment experience. Conclusion Our analysis of the personal experience of patients regarding recommended lifestyle changes associated with long-term corticosteroid treatment highlights patient difficulties and suggests different ways of improving therapeutic education.

International audience

ObjectivesThe aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.MethodsSystematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.ResultsForty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.ConclusionsIn MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.

Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses. Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase. A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8–1; p

Resume L’arthrose est le rhumatisme le plus frequent, touchant jusqu’a 15 % de la population adulte, et pourtant nous manquons de biotherapie efficace. Cette affection articulaire se caracterise principalement par la degradation de la matrice du cartilage articulaire, une synovite ainsi qu’une activation osteoclastique dans l’os sous-chondral. L’inflammation articulaire chronique contribue aux symptomes et a la progression de la maladie. Outre les mediateurs inflammatoires (chimiokines, cytokines [IL-1β] et alarmines), les microtraumatismes biomecaniques repetes et le stress oxydatif compromettent la viabilite des chondrocytes, conduisant a leur hypertrophie et a leur senescence acceleree. Les cellules souches ou stromales mesenchymateuses (CSM) sont des cellules multipotentes adultes pouvant etre isolees a partir de differents organes comme la moelle osseuse, le tissu adipeux, le cordon ombilical, le placenta. L’utilisation des CSM dans cette pathologie se justifie du fait de leurs capacites de differenciation cartilagineuse mais surtout pour leurs proprietes paracrines et immunosuppressives. Une strategie therapeutique prometteuse comprend l’injection articulaire de CSM isolees ou adherentes sur des matrices degradables. Par leurs proprietes, elles contribuent a reduire l’inflammation locale, a diminuer l’activation des monocytes, ainsi qu’a prevenir l’hypertrophie et l’apoptose chondrocytaire. Dans cette revue, nous resumons les donnees recentes sur les mecanismes d’action et les resultats cliniques des etudes pilotes suggerant que les CSM representent une avancee therapeutique credible dans l’arthrose.

OBJECTIVE The aim was to analyse the accuracy of a hand dynamometer connected to a smartphone to assess RA disease activity through the measurement of handgrip strength (HGS). METHODS Eighty-two RA patients participated in this prospective study. Three types of HGS were assessed: power (Po), pinch (Pi) and tripod (T). An interactive mobile application was developed to capture grip measures. A unilinear regression analysis between HGS and DAS28 was performed. A multivariate regression analysis to identify independent variables related to HGS was also conducted. RESULTS Sixty-three patients (76.8%) were female. Mean age was 61.3 years. At baseline, a negative correlation between the three HGS measures and DAS28 score was found, as follows: Po, r = -0.65 (95% CI: -0.76, -0.51, P < 0.001); Pi, r= -0.42 (95% CI: -0.59, -0.23, P < 0.001); and T, r = -0.47 (95% CI: -0.63, -0.29, P < 0.001). In a longitudinal analysis of 32 patients, a negative correlation between ΔPo grip and ΔDAS28 was found (r = -0.76, 95% CI: -0.88, -0.56). Po grip was independently correlated with male sex (95% CI: 1.49, 4.14, P = 0.002), whereas variables inversely correlated with Po grip were disease duration (95% CI: -2.71, -1.34, P = 0.03), patient global assessment (95% CI: -2.41, -1.1, P < 0.001) and CRP level (95% CI: -3.56, -1.08, P < 0.001). CONCLUSION HGS assessed by a hand dynamometer connected to a smartphone represents an innovative health technology solution that could prompt the self-assessment of RA disease activity in an outpatient setting.

The emergence and spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the resulting COVID-19 disease, have had a tremendous impact on public health and the world economy. Thus far, COVID-19 does not appear to be more severe in immunocompromised patients, but relevant data are scarce.1 Conversely to what was initially thought, patients with systemic lupus erythematosus (SLE) are also involved.2 3 In an article by Mathian et al ,4 some severe forms of COVID-19 infection were described in 17 patients with SLE, particularly in those with renal failure or obesity. This greater susceptibility might arise from dysregulation of ACE2 and interferon expression.5 At the same time, hydroxychloroquine (HCQ), the reference standard-of-care treatment for SLE, has emerged as a potential treatment option for COVID-19. HCQ has shown the potential to inhibit the viral replication in vitro, and several clinical trials are under way to evaluate its clinical efficacy.6 Building on the report of Mathian et al ,4 we would like to share our experience from another French university centre to further the discussion of SLE patient outcomes during the COVID-19 outbreak. Here we aim to address COVID-19 disease progression …

Background:Sarilumab, an anti-IL-6R antibody, is approved for the treatment of moderate to severe RA and shown efficacy on disease activity and patient-reported outcomes (PROs). Detailed analyses of drug efficacy from the patient point of view is important. SariPRO is a pragmatic interventional study close to the daily practice.Objectives:To assess the effectiveness of sarilumab on several PROs using the RAID (Rheumatoid Arthritis Impact of Disease) score.Methods:The SariPRO study (NCT 03449758) was a French multicenter interventional study assessing the effects of sarilumab 200 mg on PROs in patients with moderately to severely active RA with an inadequate response or intolerance to conventional synthetic or biologic DMARDs. The primary endpoint was change in total RAID score from baseline to week 24 (RAID ranges 0-10 where 10 is maximal impact). Changes from baseline for RAID, DAS28-ESR and CDAI according to baseline disease activity were analyzed as secondary outcomes. Safety was assessed by monitoring adverse events (AE). All statistical analyses were descriptive, 95% CI was given when appropriate.Results:84 patients were included in 31 centers and 62 were evaluable and analyzed for effectiveness. They had similar characteristics to the 84 patients at baseline and were as expected for an RA population initiating a biologic: mean (SD) age: 59.9 (12.4) years, 71.0% female, disease duration 9.7 (10.3) years, rheumatoid factor positivity 82.5%, ACPA positivity 86.4%, and DAS28=4.9 (11). Total RAID score decreased significantly from 5.7 (2.0) at baseline to 3.3 (2.5) at W24; mean change was -2.4 [95% CI: -3.0; -1.8]. Furthermore, this improvement was noted both for highly and less active patients at baseline: for patients with DAS28-ESR < 5.1 (n=31), mean change was -1.56 [-2.28; -0.83] and for patients with DAS28-ESR≥5.1 (n=27), mean change was -1.98 [-2.91; -1.05]. Changes in DAS28-ESR and CDAI were significant (-2.8 [-3.2; -2.4] and -15.2 [-18.5; -11.8], respectively). AEs were consistent with the safety profile of anti-IL-6R antibodies and with results from RCTs (data not shown).Conclusion:In this real world study, treatment with sarilumab during 24 weeks in RA patients led to an improvement in the total RAID score irrespective of baseline levels of disease activity. This is the first time RAID score is used as the primary endpoint in a study.References:[1]Study was sponsored by Sanofi GenzymeDisclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi, Thierry Schaeverbeke: None declared, Christine Albert: None declared, Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, marie-Christophe Boissier: None declared, Cyrille Confavreux: None declared, Gregoire CORMIER: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Elisabeth Gervais Solau: None declared, Sophie Godot: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Slim Lassoued: None declared, Thierry Lequerre: None declared, Frederic Lioté Consultant of: CME: Nordic Pharma, Christian Marcelli: None declared, Yves Maugars: None declared, Minh Nguyen: None declared, Aleth Perdriger: None declared, Yves-Marie Pers: None declared, Edouard Pertuiset: None declared, Lucile Poiroux: None declared, Carole Rosenberg: None declared, Christian Roux: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Martin SOUBRIER: None declared, Pascale Vergne-Salle: None declared, Charles Zarnitsky: None declared, Eric Fakra Consultant of: Janssen, Lundbeck, Otsuka, Sanofi, Hubert MAROTTE Grant/research support from: Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Consultant of: AbbVie, Amgen, Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Paid instructor for: Sanofi-Aventis, Speakers bureau: Sanofi-Aventis, Florence E Lévy-Weil Employee of: Sanofi Genzyme employee

Background:Joint replacement is a therapeutic option increasingly widespread among osteoarthritis (OA) patients. Besides improving operating techniques and postoperative management, it is important to pursue the best preoperative conditions in order to achieve the desired result. As physical activity (PA) potentially acts on the preoperative predictors, knowing the effect of leisure and occupational PA should be of great interest to obtain a positive outcome.Objectives:To investigate the influence of preoperative PA on the clinical outcomes of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in OA patients.Methods:Data from the Knee and Hip OsteoArthritis Long-term Assessment (KHOALA) cohort (1), a multi-regional French cohort of 878 patients with symptomatic hip and/or knee OA, were analysed. We included in our study patients undergoing THA or TKA during a 7-year-follow-up period. The level of total and leisure-time preoperative PA was measured with the Modifiable Activity Questionnaire (MAQ). Outcomes were measured one year after surgery. For the primary endpoint, quality of life (QoL) was measured with the OsteoArthritis Knee and Hip Quality Of Life questionnaire (OAKHQOL). For secondary endpoints, QoL was measured with Short Form 36 (SF-36), pain with the Visual Analogue Scale (VAS), function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and with walking distance. The population characteristics were described using frequency or mean and standard deviation (SD), depending on the distribution of the variable. Association between exposures and outcomes was calculated with a multivariate linear analysis with backward selection, adjusting for confounders (age, sex, body mass index, site of joint replacement, polyarticular OA, OA duration, comorbidities, radiological grade of OA, inclusion centre, rehabilitation after surgery, previous joint issues, instruction level). A p-value Results:150 patients were included. 58.7% underwent TKA and 41.3% THA. The mean age at the time of surgery was 66.6 years (±7.7 SD). The majority of patients were female (75%), overweight (mean BMI 29.63 kg/m2, ±5.5 SD) and had polyarticular OA (60%). 53% of patients met the World Health Organization recommendations on PA before surgery. For the primary endpoint, a high preoperative total PA was associated with a better relationship with the partner (β = 0.55, p = 0.02) one year after surgery. As for secondary endpoints, a high two-year preoperative total PA was associated with an impaired SF-36 Mental Component Summary score (β = -0.87, p = 0.02), but a longer walking distance (β = 442.81, p < 0.01). Leisure-time PA also showed a positive impact on walking distance (β = 76.25, p = 0.02), but a negative one on social functioning in SF-36 (β = -0.47, p = 0.01). No statistically significant association between preoperative PA and pain nor WOMAC was found.Conclusion:In this cohort study, the preoperative level of PA demonstrated a heterogeneous effect on the various aspects of QoL one year after THA and TKA in OA patients. Preoperative PA was directly associated with gain of function, measured as walking distance, after surgery. Considering the increasing prevalence of OA and the crucial role of PA on health, further studies on this relevant topic are needed.References:[1]Guillemin F, Rat A-C, Roux CH, Fautrel B, Mazieres B, Chevalier X, et al. The KHOALA cohort of knee and hip osteoarthritis in France. Joint Bone Spine. 2012 Dec 1;79(6):597–603.Disclosure of Interests:Enrica Vandelli: None declared, Claire Duflos: None declared, Sandrine Akouete: None declared, Francis Guillemin Grant/research support from: Francis Guillemin received a grant from Expanscience paid to his institution., Anne-Christine Rat: None declared, Yves-Marie Pers: None declared

Background:Telemedicine has found wider application in chronic diseases for encouraging tight home-monitoring in order to improve patients’ outcome (Smolen et al. 2017).In previous studies, a high feasibility and high patient-satisfaction rate was found as well as the evidence for a superior or equal effectiveness of telemedicine compared to the standard face-to-face approach, however the results were weakened by some methodological biases and wide heterogeneity of interventions, thus preventing to draw definitive conclusions (Piga et al. 2017; Najm, Gossec, et al. 2019).Objectives:In rheumatoid arthritis (RA), telemedicine may allow a tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician’s interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA.Methods:A 6-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new Disease Modifying Anti-Rheumatic Drug (DMARD) therapy. Two groups were established: “connected monitoring” and “conventional monitoring”. The primary outcome was the number of physical visits between baseline and 6 months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional, and health status scores (SF-12).Results:Of the 94 randomized patients, 89 completed study: 44 in the “conventional monitoring” arm and 45 in the “connected monitoring” arm. The total number of physical visits between baseline and 6 month was significantly lower in the “connected monitoring” group (0.42 ± 0.58 versus 1.93 ± 0.55; pConclusion:According to our results, a connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment.References:[1] Najm, Aurelie, Laure Gossec, Catherine Weill, David Benoist, Francis Berenbaum, and Elena Nikiphorou. 2019. “Mobile Health Apps for Self-Management of Rheumatic and Musculoskeletal Diseases: Systematic Literature Review.”JMIR MHealth and UHealth7 (11): e14730.https://doi.org/10.2196/14730.[2] Piga, Matteo, Ignazio Cangemi, Alessandro Mathieu, and Alberto Cauli. 2017. “Telemedicine for Patients with Rheumatic Diseases: Systematic Review and Proposal for Research Agenda.”Seminars in Arthritis and Rheumatism47 (1): 121–28.https://doi.org/10.1016/j.semarthrit.2017.03.014.[3] Smolen, Josef S, Robert Landewe, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, et al. 2017. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2016 Update.”Annals of the Rheumatic Diseases76 (6): 960–77.https://doi.org/10.1136/annrheumdis-2016-210715.Disclosure of Interests:None declared

Background:The tremendous size of the 2013-2016 West African outbreak of Ebola virus disease (EVD) resulted in a sizeable population of survivors, many reporting short-term sequelae such as arthralgia and myalgia.Objectives:We aimed to report a detailed and long-term description of patients’ musculoskeletal (MS) symptoms.Methods:We performed a cross-sectional study following systematic rheumatological screening of patients included in the Postebogui cohort (Conakry district). We used regression models to establish the magnitude of EVD as a risk factor for developing chronic MS pain by comparison with a control cohort and to establish risk factors for developing MS pain among survivors.Results:The study included 313 patients (55.6% female), with a median age of 28.2 years (IQR 21-37), and a median time from ETC discharge to rheumatological visit of 26.2 months (IQR 23-30). Chronic MS pain was reported in 216 (69%) patients, and was predominantly mechanical (48%). Enthesis and painful peripheral joints were largely involved (91%) with symmetrical distribution. Previous Ebola infection was a major risk factor for chronic MS pain (aOR, 6.662 [95% CI, 4.522–9.921]). Among survivors, increasing age (OR 1.14, 95% CI 1.08-1.22) and female gender (OR 3.58, 95% CI 1.22-11.80) were both associated with persistent MS pain, while myalgia experienced during the acute phase of EVD appeared protective (OR 0.14, 95% CI 0.04-0.42).Conclusion:Our study provides the most accurate long-term description of MS disorders among Ebola survivors. Joint and muscle pain sequelae are frequent and require specialized care.Disclosure of Interests:None declared

International audience; Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16–0.61), p = 0.001). No association was found with any of the other SNPs tested.

International audience

Objective.: Previous studies show that arthralgia is the most common symptom experienced by Ebola virus disease (EVD) survivors. Nevertheless, specific analyses of rheumatological sequelea are still lacking. Methods.: The Postebogui study is a prospective, multicentre cohort aiming to evaluate the long-term outcomes of EVD survivors infected during the 2014-15 outbreak in Guinea. Of the 216 participants enrolled in the study in October 2015, 44 patients with arthralgia/myalgia underwent a physical examination by a rheumatologist (the Eborheum cohort). Data were collected using a standardized questionnaire. Results.: In the Eborheum cohort, 61% of patients were female, the median age was 31.1 years, and the median time from Ebola Treatment Centre discharge was 8.8 months. Pain manifestation started after Ebola infection in all but one patient. Patients had mainly both mechanical and inflammatory pain (45%) and low back pain (77%). All patients reported pain in at least one peripheral joint. Pain in large joints was more frequently reported than in small joints (73 vs 41%). Oligo- and polyarticular presentations were similar, with symmetrical pain distribution. Furthermore, 36 patients had at least one painful 18-tender point count, most of whom reported extensive pain (n = 19) and symmetrical distribution (91%). Diagnoses were mainly non-specific musculoskeletal disorders (59%) and mechanical back pain (52%). No polyarthritis was observed. We found a higher percentage of depressed patients compared with the remaining Postebogui group (42 vs 11%; P < 0.001). Conclusion.: Results from the study come from the first complete rheumatological examination of a cohort of EVD survivors, nearly 9 months after Ebola Treatment Centre discharge. Importantly, we found that patients with arthralgia/myalgia included in the Eborheum cohort were more likely to experience depression than survivors not reporting these symptoms, highlighting the impact of pain symptoms among survivors.

To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice.We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test.Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P0.01) compared to the younger patient group (65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups.In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results.

Backgrounds and objectives Osteoarthritis (OA) is the most common rheumatic disease affecting all joint tissues and Transforming Growth Factor β (TGFβ) pathway dysregulation in bone marrow mesenchymal stem cells (MSCs) has been proposed to be involved in OA physiopathology. Based on secretome analysis of MSCs, we identified several TGFβ family members and focused our attention on Transforming Growth Factor β-Induced (TGFβI), a poorly studied extracellular matrix (ECM) component. Materials and methods Human bone marrow MSCs were isolated from OA patients (OA-MSCs) and healthy donors (H-MSCs) while chondrocytes were isolated from OA patients (OA-CH). Chondrogenic differentiation of MSCs was induced in micropellet for 21 days. TGFβI expression was analysed by RT-qPCR and ELISA. Murine articular chondrocytes were isolated from 3 days old C57/BL6 mice and OA-like murine chondrocytes were obtained by addition of 1 ng/mL IL1β for 24 hour. Transfection of siRNA directed against TGFβI (siTGFβI) was performed using oligofectamine. The collagenase-induced murine model of OA was used for immunohistochemical analysis of cartilage and RNA extraction with TRIzol and acid phenol. Results In humans, TGFβI mRNA expression was 2.5 fold lower in OA-MSCs than in H-MSCs and 10 fold lower in OA-MSCs than in OA-CH. We also found out that TGFβI was highly induced (by a 10 fold factor) during the first three days of chondrogenic differentiation but decreased to reach levels similar to those found in MSCs. In the mouse, immunohistochemical analysis revealed high expression of TGFβI in healthy cartilage as compared to OA cartilage. In murine MSCs, expression of TGFβI is 3.8 fold lower than in chondrocytes. In OA-like chondrocytes, characterised by reduced expression of anabolic markers and increased levels of catabolic markers, TGFβI mRNA levels were significantly lower than in healthy chondrocytes. Rapid decline of TGFβI expression was also observed in OA-like dedifferentiated chondrocytes. Finally, transfection of siTGFβI in murine chondrocytes resulted in alteration of their metabolic activity. Conclusion Altogether, our results indicate that expression of TGFβI is higher in articular cartilage than in MSCs, and loss of TGFβI is associated with OA phenotype. TGFβI might be a key regulator of joint homeostasis involved in chondrogenesis and ECM integrity.

International audience; Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a 'window of opportunity' for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission.

To the Editor: Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in the longterm treatment of connective tissue disease (CTD) and are usually considered safe1. However, these therapies may cause serious adverse events2, including cardiac toxicity3. The cardiomyopathy induced by an antimalarial drug might mimic the cardiac involvement of Fabry disease (FD), a genetic storage disorder that causes a deficiency of a lysosomal enzyme, alpha galactosidase A (GLA). Indeed, CQ and HCQ provoke a dysfunction in the lysosomal enzymes, leading to the impairment of intracellular degradation processes in conjunction with the accumulation of pathological metabolic products4,5. The cardiac presentation of these 2 diseases is close regarding the clinical symptoms as well as the imaging and pathological findings. We report the case of a patient, treated longterm with HCQ, with cardiac disorders revealing FD. A 61-year-old woman was diagnosed 20 years ago for a CTD with dermatological disorders: alopecia, skin rash, and joint pain. The antinuclear antibodies (ANA) were positive at 1/100. Anti-SSa/Ro and anti-dsDNA antibodies were negative. The … Address correspondence to Dr. Y.M. Pers, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier, France. E-mail: ympers2000{at}yahoo.fr

International audience; A 43-year-old man was diagnosed with an Eosinophilic fasciitis with cutaneous and articular involvement. The patient experienced an early response with high-dose corticosteroids achieving a global remission of disease. Nevertheless, during the steroids tapering phase, he presented a new flare and subsequently developed a corticosteroid refractory disease. The addition of Methotrexate in monotherapy then associated with an anti-tumor necrosis factor agent did not show any additional benefit. Therefore Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, was initiated achieving an immediate response that persists after 36 months of follow-up. The use of this biological agent allows prednisone withdrawal at 3 months and remission of both articular and cutaneous manifestations at 6 months. This report describes for the first time the efficacy of an anti interleukin-6 agent in Eosinophilic fasciitis treatment

We report the case of a 38-year-old man who presented with severe diarrhea, weight loss of 10 kg, ankles paresthesia and severe motor weakness in the left fibular nerve territory after introduction of azathioprine and corticosteroid for proteinuria. Coloscopy and gastroscopy revealed a typical aspect of Whipple disease (WD), associated with both positive PAS staining and specific immunohistochemistry. T. whipplei PCR results were positive in blood, faeces, saliva and duodenal biopsy specimens. Diagnosis of WD with systemic manifestations was retained and doxycycline plus hydroxychloroquine therapy were started. This treatment improved joint pain, and skin and intestinal symptoms. One month later, our patient presented with fever and an important inflammatory syndrome (CRP 150 mg/dL and 16.8 10 9 /L leukocytes), while no infection was found despite a thorough review. We concluded it was an immune reconstitution inflammatory syndrome (IRIS). Manifestations persisted despite increasing corticosteroids and thalidomide (200 mg/day) was introduced with good efficacy on these symptoms. WD may be revealed by non-specific symptoms such as weight loss or arthralgia, but also by many other misleading signs. Our observation illustrates the highly polymorphic clinical presentation of WD, and the diagnostic difficulties that may arise. This is also a new report of thalidomide effectiveness in IRIS in WD.

Aim To evaluate fear, beliefs, catastrophizing and kinesiophobia in chronic low back pain patients about to begin a training programme in a rehabilitation centre. Patients and methods Fifty chronic low back pain patients (including both males and females) were assessed in our physical medicine department. We used validated French-language scales to score the patients’ pain-related disability, quality of life and psychosocial factors. Results Seventy percent of the patients had a major functional disability (i.e., a Roland–Morris Scale score over 12) and nearly 73% reported an altered quality of life (the daily living score in the Dallas Pain Questionnaire). Pain correlated with functional impairment and depression but not with catastrophizing or kinesiophobia. Disability was correlated with catastrophizing and kinesiophobia. Conclusion Psychosocial factors are strongly associated with disability and altered quality of life in chronic low back pain patients. Future rehabilitation programs could optimizing patient management by taking these factors into account.

Anti-Ma2 antibodies belong to a family of onconeuronal antibodies that target proteins expressed in brain, testis and several tumors. Previously observed in patients presenting with limbic encephalitis, they seem to be associated with several other paraneoplastic syndromes. We report the case of a 73-year-old woman presenting sensory and motor neuropathy associated with non-small-cell lung cancer who had Ma2-antibodies.

Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 106 cells), medium dose (10 × 106), and high dose (50 × 106). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. Significance Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

International audience; Objective. The aim of this study was to evaluate the impact of introducing tocilizumab (TCZ) as co-therapy with CS in patients with RA.Methods. This study was an open, observational, retrospective multicentre study. RA patients treated with oral CS for >3 months who started treatment with TCZ between December 2009 and June 2011 in five centres were included. Variables included demographic data, disease history, co-treatments, disease activity and dose of CS at inclusion and at weeks 4, 8, 12 and 24. The evolution of disease activity and of the dose of CS (analysis of variance with repeated measures) were analysed, searching for factors correlated with changes in the dose of CS.Results. Inclusion of 130 patients [women 80.8%, mean age 56.7 years (S.D. 14.0), RA duration 16.3 years (S.D. 10.4), mean baseline 28-joint DAS (DAS28) 5.1 (S.D. 1.4), mean baseline dose of CS 10.0 mg/day (S.D. 8.2) prednisone equivalent. Decreases in the mean daily dose of CS and in the DAS28 were observed during follow-up [respectively 6.5mg (S.D. 4.8) at week 24 (P < 0.0001) and 3.0mg (S.D. 1.4) at week 24 (P < 0.0001)]. The only variable that correlated with the decrease in the dose of CS was the initial dose of the drug (r = 0.82, P < 0.001).Conclusion. The introduction of TCZ led to rapid and long-lasting CS sparing that did not correlate with the reduction in disease activity. It is possible that in patients treated with high-dose CS, the main objective of the clinician is to reduce dosage of CS rather than RA activity.

International audience; Background: In 2009, a worldwide supply constraint of imiglucerase led to treatment modifications or interruptions for patients with Gaucher disease (GD) type 1. In France, joint treatment recommendations were issued to protect the most vulnerable patients. This observational study evaluated the impact of imiglucerase treatment modifications on the clinical and biological course of GD. Methods: Retrospective data on patients' characteristics, treatment, clinical and biological parameters from 01 June 2009 to 31 October 2010 were collected during a single visit.Methods: Retrospective data on patients’ characteristics, treatment, clinical and biological parameters from 01 June 2009 to 31 October 2010 were collected during a single visit.Results: Ninety-nine GD1 patients, aged 7–84 years, were included (median age 47 years); 10 were children. Patients experienced a median of 4 different treatment modifications. Median change from pre-supply constraint dose (92 U/kg/4-weeks) was −69, −51, −29 and −60 U/kg/4-weeks at 3, 6, 9 and 12 months after first modification, respectively, with imiglucerase discontinuation reported for 70%, 47%, 29% and 55% of patients at these timepoints. Replacement with another ERT was reported for 35 patients. Results show a statistically significant decrease in hemoglobin (−0.8 g/L/month) and platelets (−5905.103/mm3/month) and an increase in chitotriosidase (+537 nmol/mL/h/month) and angiotensin-converting enzyme (+4 IU/L/month) in the subgroup of 61 patients who discontinued treatment for at least 3 months; this magnitude of change was not seen in the subgroup (32 patients) treated with reduced imiglucerase for at least 3 consecutive months. GD-related events were spontaneously reported by the study investigators for 39% of the whole study population, including asthenia/fatigue (8%), bone infarction and bone pain (4% each), and hepatomegaly (3%). A Kaplan-Meier estimate of the probability for a patient to present a bone, hematological or visceral event during the constraint was 37% for patients who discontinued the treatment and 10% for patients treated with a reduced imiglucerase dose.Conclusion: The release of recommendations and individuals’ close follow-up allowed satisfactory management of patients during the imiglucerase supply constraint in France. This study suggests that during this period, lowering the dose of imiglucerase had less impact on the outcomes of patients than interrupting treatment. However, general effects (such as fatigue, bone pain) reported in some patients, emphasize the importance of maintaining appropriate individualized dosing.

Objective.To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA).Methods.We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed.Results.No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16–1.24, p = 0.13 and OR 1.19, 95% CI 0.31–4.48, p = 0.78 for BMI 25–30 kg/m2 and BMI > 30 kg/m2, respectively, compared to BMI < 25 kg/m2).Conclusion.Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

International audience

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 29 mai 2014

Supplementary data are available at Rheumatology Online.; International audience; Objective: The objective of this study was to identify predictors of response and remission to tocilizumab (TCZ) in RA patients seen in daily routine clinical practice.Methods: The efficacy of TCZ was evaluated after 12 and 24 weeks of treatment by the European League Against Rheumatism (EULAR) response criteria. Regression analysis was performed to study the association between remission or EULAR response and the following characteristics: gender, age, current smokers, prior cardiovascular disease (CVD), 28-joint disease activity score (DAS28), CRP, RF or ACPA positivity, combination therapy with DMARDs and TCZ as the first biological therapy or after failure of at least one biological therapy.Results: In total, 204 patients were included with a mean DAS28 score of 5.14. EULAR response and remission were obtained in 86.1% and 40% of patients, respectively, at week 24. In multiple regression analysis, a high baseline CRP level [odds ratio (OR) 4.454 (95% CI 1.446, 13.726)] was significantly associated with EULAR response at week 24 and, inversely, age >55 years [OR 0.285 (95% CI 0.086, 0.950)] and prior CVD [OR 0.305 (95% CI 0.113, 0.825)] were significantly associated with lower EULAR response at week 24. Older age was also associated with less remission at week 24 [OR 0.948 (95% CI 0.920, 0.978)]. No additional effectiveness was found when TCZ was used in combination with a DMARD or when patients were naive to biological agents.Conclusion: In daily practice we identified three predictors of a better response for TCZ therapy in RA: a younger age, a high baseline CRP level and no history of CVD.

Myositis ossificans circumscripta (MOC) is a form of heterotopic ossification in extraskeletal soft tissues that is benign, but may appear clinically and radiologically as a malignant neoplasm1. An 18-year-old woman had sudden pain in her left thigh with functional impairment, without trauma. Examination revealed an indurated mass on the upper third of the thigh. Laboratory analyses were normal except for a C-reactive protein level at 35 mg/l …