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Resume Objectifs Etablir sous l’egide de la Societe francaise de rhumatologie (SFR) des recommandations sur les traitements pharmacologiques de la gonarthrose. Methodes Le groupe de bibliographie a realise une analyse de la litterature sur l’efficacite et la tolerance de chaque traitement. Ce groupe a rejoint un groupe de travail pluridisciplinaire pour elaborer les recommandations par vote et recueil du niveau d’accord. Chaque recommandation a fait l’objet d’une force de recommandation et d’un niveau d’evidence. Un groupe de lecture a donne son niveau d’agrement. Resultats Cinq principes generaux ont ete emis sur : (1) la necessite de combiner traitements pharmacologiques et non pharmacologiques, (2) la personnalisation de la prise en charge, (3) l’objectif symptomatique et/ou fonctionnel des traitements pharmacologiques, (4) la necessite d’une reevaluation medicale reguliere des traitements et (5) la discussion d’une arthroplastie en cas d’echec du traitement medical. Six recommandations ont concerne les traitements oraux : (1) le paracetamol qui ne doit pas necessairement etre prescrit de maniere systematique et/ou continue, (2) les AINS, eventuellement en 1re intention, (3) les opioides faibles, (4) les opioides forts et (5) les anti-arthrosiques symptomatiques d’action lente et, (6) hors AMM, la duloxetine. Deux recommandations ont concerne les topiques (AINS et capsaicine Conclusion Il s’agit des 1res recommandations de la SFR sur la prise en charge pharmacologique de la gonarthrose.

Resume Objectifs Les inhibiteurs de l’interleukine (IL)-1β, efficaces dans les crises de goutte, sont recommandes en cas de contre-indications a la prise en charge standard, notamment insuffisance renale chronique (IRC) de stade 4 ou 5. Or, il existe peu de donnees disponibles sur l’efficacite et la securite de ces agents dans cette population de patients. Nous avons souhaite explorer l’efficacite et la securite de l’anakinra utilise pour traiter les crises de goutte chez des patients presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale. Methodes Cette etude retrospective menee dans trois centres universitaires a inclus des patients consecutifs presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale qui prenaient de l’anakinra en traitement d’une arthrite goutteuse aigue et avaient effectue au moins une visite de suivi. L’efficacite, la survenue d’infections et les variations de la fonction renale ont ete consignees. Resultats Sur les 31 patients inclus (24 hommes, âge moyen 72 ± 11 ans), 25 n’avaient pas subi de transplantation et presentaient une IRC de stade 4 ou 5 (estimation du debit de filtration glomerulaire moyen [eDFG] selon la formule MDRD 22,7 ± 6,5 mL/min/1,73 m2) et 6 avaient subi une transplantation renale (eDFG moyen 41,5 ± 22,8 mL/min/1,73 m2). La duree mediane de la goutte etait de 3,5 ans et le taux moyen d’uricemie de 8,7 mg/dL. Vingt-et-un patients (68 %) presentaient des tophi et 21, une arthropathie goutteuse. L’anakinra a ete efficace chez tous les patients (EVA final 10 et CRP finale 10 mg/L). Dix patients (32 %) etaient dependants de l’anakinra (c.-a-d. qu’un traitement prolonge d’anakinra etait necessaire). Une infection grave a ete enregistree chez une seule patiente, trois mois apres l’instauration de l’anakinra. Aucune variation significative de la fonction renale n’a ete observee. Conclusion L’anakinra peut constituer une option therapeutique sure chez les patients goutteux presentant une IRC a un stade avance. Des etudes comparatives randomisees supplementaires sont necessaires pour confirmer nos resultats.

To establish recommendations for pharmacological treatment of knee osteoarthritis specific to France.On behalf of the French Society of Rheumatology (SFR), a bibliography group analyzed the literature on the efficacy and safety of each pharmacological treatment for knee osteoarthritis. This group joined a multidisciplinary working group to draw up recommendations. Strength of recommendation and quality of evidence level were assigned to each recommendation. A review committee gave its level of agreement.Five general principles were established: 1) need to combine pharmacological and non-pharmacological treatments, 2) personalization of treatment, 3) symptomatic and/or functional aim of pharmacological treatments, 4) need to regularly re-assess the treatments and 5) discussion about arthroplasty if medical treatment fails. Six recommendations involved oral treatments: 1) paracetamol should not necessarily be prescribed systematically and/or continuously, 2) NSAIDs, possibly as first-line, 3) weak opioids, 4) strong opioids, 5) symptomatic slow-acting drugs of osteoarthritis, and 6) duloxetine (off-label use). Two recommendations involved topical agents (NSAIDs and capsaicin1%). Three recommendations involved intra-articular treatments: corticosteroid or hyaluronic acid injections that can be proposed to patients. The experts did not draw a conclusion about the benefits of platelet-rich plasma injections.These are the first recommendations of the SFR on the pharmacological treatment of knee osteoarthritis.

Objectives Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4–5 chronic kidney disease (CKD) patients. However, efficacy and safety data regarding these agents are lacking in this population. We aimed to investigate the efficacy and safety of anakinra for the treatment of gout flares in patients with stage 4–5 CKD or renal transplantation. Methods This retrospective study encompassing 3 academic centres included consecutive patients with stage 4–5 CKD or kidney transplantation who received anakinra for the treatment of acute gouty arthritis and completed at least one follow-up visit. Efficacy, occurrence of infection, and renal function variations were recorded. Results Of the 31 included patients (24 men, mean age 72 ± 11 years), 25 were non-transplant subjects with stage 4–5 CKD (mean estimated glomerular filtration rate, MDRD formula (eGFR) 22.7 ± 6.5 mL/min/1.73 m 2 ), and six had undergone kidney transplantation (mean eGFR 41.5 ± 22.8 mL/min/1.73 m 2 ). Median gout duration was 3.5 years, and the mean serum urate (SUA) level was 8.7 mg/dL. Twenty-one (68%) patients had tophi, and 21 had gout arthropathy. Anakinra was efficacious in all patients (final VAS 10 and CRP level 10 mg/L). Ten patients (32%) were anakinra dependent (i.e., required prolonged treatment with anakinra). A serious infection was recorded in only one patient, occurring 3 months after starting anakinra. No significant variation in renal function was observed. Conclusion Anakinra may be a safe therapeutic option for gout patients with advanced CKD. Further randomized controlled studies are required to confirm our results.

Objective To explore acceptance and retention rate of biosimilar CT-P13 after switching from originator infliximab (OI) in patients with various rheumatic diseases. Methods Patients with stable rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA) under OI were proposed to switch to CT-P13 at the same regimen. A prospective cohort of infliximab-naive patients beginning CT-P13 and a retrospective cohort of patients treated with OI were used as controls. The primary outcome was to evaluate the retention rate of CT-P13. Secondary outcomes were the switch acceptance rate, reasons of failure and safety. Results Switch was proposed to 100 patients and accepted by 89 of them (63 AS, 12 PsA and 14 RA). After a median follow-up of 33 weeks, 72% of patients were still treated with CT-P13. This retention rate was significantly lower than the one found in our retrospective and prospective control cohorts: 88% and 90% respectively (P-value = 0.0002). Within patients who asked to be reswitched to OI, 13/25 (52%) presented clinical disease activity, one developed serum sickness and 11 (44%) presented no objective activity. A subanalysis excluding these 11 patients abrogated difference in retention rates between the 3 cohorts (P-value = 0.453). After reswitching to OI, patients without objective disease activity claimed to recover original efficacy. Conclusions Retention rate was lower after switching from OI to CT-P13 compared to our control cohorts. However, this difference faded after excluding patients without objective clinical activity, suggesting a reluctance of patients to the switch and a negative perception of the biosimilar.

ObjectivesTo evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response.MethodsThis was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management.ResultsFrom September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; PConclusionSince ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.

Background Immune checkpoint inhibitors (ICIs) are revolutionizing the treatment of some advanced cancers. Gut microbiota has emerged as an important component of anti-tumoral response and can also be related to the occurrence of immune-related adverse events (irAEs). It has recently been shown that antibiotic treatment given at the initiation of ICI therapy had a dramatic impact on microbiota that compromised the anti-tumoral effect of ICIs (1). Objectives To evaluate whether co-medications known to have a potential impact on gut microbiota may alter ICI efficacy and/or irAE occurrence when given at ICI onset. Methods This was a retrospective cohort study including all cancer patients who received ICIs at our institution from May 2015 to September 2017. Co-medications given to the patients within one month before or one month after the first administration of ICI were extracted from medical records on the basis of a predefined list of medications known to impact gut microbiota. The tumour response, occurrence of irAEs and patient outcomes were assessed on a regular basis. Overall survival (OS) has been considered from the start of ICI therapy. Results 635 patients (70% male, mean age 64.5 years) were included, of whom 293 had melanoma, 150 had advanced non-small cell lung cancer and 83 had renal carcinoma. A previous autoimmune disorder was present in 8% of patients, mainly rheumatic and endocrine diseases. Psychotropic drugs (41.1%), proton pump inhibitors (PPIs) (37.3%), angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs) (32%), glucocorticoids (GC) (24.2%), antibiotics (21.4%), statins (20.8%) and morphine (20.6%) were the most co-prescribed medications. Baseline GC use, when ≥ 10mg of prednisone equivalent, was associated with a significant decrease in OS (median 4.5 months versus 24.3 months; p Conclusion As many of these treatments are used by rheumatologists, one should be aware of their potential detrimental effect when used at ICI initiation, that sometimes could have been avoided. Reference [1] Routy B et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91-97. Disclosure of Interests None declared

Resume Objectifs Etudier l’acceptabilite et le taux de maintien de l’infliximab biosimilaire CT-P13 (Inflectra©) apres switch a partir de l’infliximab original (IO) chez des patients atteints de rhumatismes inflammatoires. Methodes Il a ete propose a des patients atteints de polyarthrite rhumatoide (PR), de spondylarthrite ankylosante (SA) ou de rhumatisme psoriasique (RhPso) controles sous IO, un switch pour le CT-P13 en poursuivant le meme schema therapeutique. Une cohorte prospective de patients naifs d’infliximab debutant le CT-P13 et une cohorte historique de patients traites par IO ont ete utilisees comme groupes temoins. L’objectif principal etait d’etudier le taux de maintien du CT-P13. Les objectifs secondaires etaient l’etude de l’acceptabilite, des raisons d’echec du switch et de la tolerance. Resultats Le switch a ete propose a 100 patients et accepte par 89 d’entre eux (63 SA, 12 RhPso et 14 PR). Apres un suivi median de 33 semaines, 72 % des patients etaient toujours traites par CT-P13. Ce taux de maintien etait significativement plus faible que celui retrouve dans les cohortes temoins historique et prospective : 88 % et 90 % respectivement (p = 0,0002). Parmi les patients demandant un retour a l’IO, 13/25 (52 %) presentaient une activite clinique de leur maladie, un patient a presente une maladie serique et 11 (44 %) ne presentaient pas d’activite objective. Une analyse excluant ces 11 patients faisait disparaitre la difference de taux de maintien entre les 3 cohortes (p = 0,453). Apres retour a l’IO, les patients sans activite clinique objective retrouvaient tous leur etat anterieur. Conclusion Le taux de maintien etait significativement plus faible apres le switch de l’IO vers le CT-P13 par rapport aux cohortes temoins. Cependant, cette difference disparaissait apres exclusion des patients sans activite clinique objective, suggerant une reticence des patients pour le switch et une perception negative du biosimilaire.

Resume Les notables progres realises au cours des dernieres decennies dans la connaissance des mediateurs et des circuits impliques dans la genese et le controle de la douleur n’ont pas debouche a ce jour sur la decouverte de medicaments innovants. Or nous manquons d’antalgiques performants et surs, d’ou les espoirs suscites par les anticorps monoclonaux ciblant le nerve growth factor (NGF) apres que des travaux experimentaux eurent revele le role cle de cette neurotrophine dans le declenchement et l’entretien d’un large eventail de syndromes algiques. Le tanezumab est la molecule pionniere dans le domaine et la plus avancee dans le developpement clinique. Les donnees disponibles attestent l’efficacite des anti-NGF dans l’arthrose symptomatique ; des resultats plus contrastes ont toutefois ete rapportes dans la lombalgie chronique commune, les douleurs neuropathiques et un modele de douleurs dysfonctionnelles (syndromes pelviperineaux chroniques). Mais la survenue d’arthropathies destructrices chez des patients traites decida l’Agence etasunienne, The Food and Drug Administration (FDA), a suspendre les essais des anti-NGF dans les affections non cancereuses en 2010. Sur proposition d’une commission consultative (Arthritis Advisory Committee) qui avait procede a l’analyse approfondie du rapport benefice/risques des anti-NGF, la FDA autorisa la reprise, sous conditions, des essais therapeutiques en aout 2012. Des etudes complementaires ayant etabli la neurotoxicite des anti-NGF chez l’animal, la FDA prononca un second interdit en decembre de la meme annee. Bien que les negociations entre la FDA et les firmes concernees aient finalement permis de definir les indications et le cadre dans lesquels les futurs essais pourront etre conduits, l’avenir des anti-NGF reste incertain.

Objectives: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. Methods: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. Results: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. Conclusion: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.

Background Retention rate, efficacy, and safety of abatacept (ABA) was compared between patients with rheumatoid arthritis receiving ABA as monotherapy to those in combination ABA + conventional synthetic DMARD (csDMARD). Methods The patients were obtained from the ORA registry. The retention rate was analysed in two ways: (1) therapeutic strategy retention, in which the addition of a csDMARD was considered to indicate failure of the monotherapy strategy; and (2) ABA retention, which was assessed by the discontinuation of ABA regardless of other treatment modifications. Efficacy and safety were compared between ABA initiated alone and ABA used in combination with a csDMARD. Results The retention rate at month 6 (M6) was evaluated in 569 patients. A significant difference was identified in the retention rate between the ABA monotherapy strategy and the ABA + csDMARD strategy (58.5 % [110/188] vs. 68 % [258/381], respectively, p = 0.031). No significant difference was identified in the ABA retention rate initiated either as a monotherapy or in combination with csDMARDs (75 % [142/188] vs. 76 % [291/381], respectively, p = 0.824). Data regarding ABA efficacy were available for 444 patients. There was no significant difference in the responder proportion after 6 months of treatment between ABA monotherapy and ABA + csDMARD treatment (60.2 % [88/146] vs. 60 % [179/298], respectively, p = 0.967). Conclusions This “real-life” analysis, which is relevant for bedside practice, emphasised the satisfactory efficacy and safety of ABA used in monotherapy, which provides an acceptable alternative when csDMARDs are undesirable.

Resume De nombreux medicaments ont ete testes dans la lombalgie commune. Si l’on s’en tient aux formes chroniques, il n’est finalement que les anti-inflammatoires non steroidiens (AINS), l’association paracetamol-tramadol, les antidepresseurs non selectifs de la recapture de la serotonine et des injections rachidiennes de corticoides ou d’anesthesiques locaux qui ont peu ou prou demontre leur superiorite antalgique par rapport au placebo. Encore cette efficacite est-elle modeste et limitee a la douleur, les AINS semblant seuls capables d’ameliorer l’incapacite fonctionnelle. Il apparait neanmoins que l’evolution de la lombalgie est generalement favorable, quelle que soit la therapeutique mise en œuvre, y compris un placebo. Par ailleurs, le benefice du traitement est eminemment variable d’un essai a l’autre. Cela s’explique, au moins en partie, par l’heterogeneite des malades inclus dans les essais, et pose la question d’une selection plus rigoureuse des patients qui prenne notamment en compte les diverses composantes, nociceptives, dysfonctionnelles, voire neuropathiques, du syndrome algique.

Objective A survey was performed in 5 European countries (France, Germany, Italy, Portugal, and Spain) to estimate the prevalence of fibromyalgia (FM) in the general population. Methods In each country, the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ) was administered by telephone to a representative sample of the community over 15 years of age. A positive screen was defined as the following: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and the 2-fatigue criteria (LFESSQ-6). The questionnaire was also submitted to all outpatients referred to the 8 participating rheumatology clinics for 1 month. These patients were examined by a rheumatologist to confirm or exclude the FM diagnosis according to the 1990 American College of Rheumatology classification criteria. The prevalence of FM in the general population was estimated by applying the positive-predictive values to eligible community subjects (ie, positive screens). Results Among rheumatology outpatients, 46% screened positive for chronic widespread pain (LFESSQ-4), 32% for pain and fatigue (LFESSQ-6), and 14% were confirmed FM cases. In the whole general population, 13 and 6.7% screened positive for LFESSQ-4 and LFESSQ-6, respectively. 3The estimated overall prevalence of FM was 4.7% (95% CI: 4.0 to 5.3) and 2.9% (95% CI: 2.4 to 3.4), respectively, in the general population. The prevalence of FM was age- and sex-related and varied among countries. Conclusion FM appears to be a common condition in these 5 European countries, even if data derived from the most specific criteria set (LFESSQ-6) are considered.

Background A 42-year-old man with a 10-year history of HLA-B27-positive ankylosing spondylitis presented with upper abdominal pain and nausea after receiving oral ketoprofen 200 mg/day. His gastrointestinal symptoms did not improve with the addition of ranitidine 150 mg twice daily. He had previously responded well to conventional nonsteroidal anti-inflammatory drugs. Investigations Physical examination, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, radiography, laboratory tests, upper gastrointestinal endoscopy, histopathologic examination and culture of biopsy specimens. Diagnosis Helicobacter pylori-positive duodenal ulcer. Treatment For eradication of H. pylori: omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily for 1 week. For ankylosing spondylitis: diclofenac 150 mg/day in combination with omeprazole 20 mg/day for 2 months.

Background: Diary recording of pain and disabling activities in osteoarthritis (OA) is widely recommended, but, to our knowledge, its impact on symptoms has not been investigated. Exercise programmes have been shown to be effective when patients are closely supervised by nurses or physiotherapists; however, data are lacking on the efficacy of an unsupervised home based exercise regimen in patients with OA. Objectives: To evaluate the clinical efficacy of patient administered assessment tools and an unsupervised home based exercise programme alone or in combination in patients with OA. Methods: The study was a 24 week, open cluster randomised controlled trial with a factorial design. Rheumatologists (n = 867) were assigned to four groups according to the treatment given: standardised tools (ST; n = 220), exercises (EX; n = 213), both tools and exercises (ST+EX; n = 213), or usual care (n = 221). Each rheumatologist was to enrol four patients who met the American College of Rheumatology criteria for OA (three with knee OA, one with hip OA). "Tools" consisted of weekly recording of pain and disabling activities in a diary. A home based exercise programme was performed daily at least four times per week with the aid of videotape and booklet. In addition to exercise and asessment, all patients received 12.5 mg or 25 mg of the non-steroidal anti-inflammatory drug rofecoxib once daily. Outcome variables were: pain (measured on a visual analogue scale, 0–100); Western Ontario and McMaster Universities Osteoarthritis Index, function subscale (0–100); and patient assessment of the quality of care (0–100). Results: Overall, 2957 patients with OA (2216 knee, 741 hip) were included. After 24 weeks, both pain and function improved in the ST, EX, ST+EX, and usual care groups (mean (SD) −17 (27), −20 (29), −15 (27), −19 (29); and −11 (19), −12 (19), −10 (19), −11 (20), respectively), without significant differences between groups. However, patients in the EX and ST+EX groups were more likely to agree that their rheumatologist had done his best to preserve their functional and physical activities. Conclusion: Although patients’ assessments favoured the exercise programme, results from this study failed to demonstrate a short term symptomatic effect of the two non-pharmacological treatments (weekly recording of condition and exercise) in patients with OA concurrently receiving nonsteroidal anti-inflammatory drugs.

Background: Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR standing committee for clinical trials met in 1998 to determine the methodological and logistical approach required for the development of evidence-based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available therapies for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. Methods: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and key words. All European language publications in the form of systematic reviews, meta-analyses, randomized-controlled trials, controlled trials and observational studies were included. During stage three all of the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and where practical the numbers needed to treat (NNT) and the effect size (ES) for each therapy was calculated. The fourth stage involved determination of key clinical propositions by expert consensus employing a Delphi approach. The final stage involved ranking of these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. Results: Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. Conclusions: These are the first clinical guidelines on knee OA to combine an evidence-based approach and a consensus approach across a wide range of treatment modalities. It is apparent that only certain clinical propositions are supported by substantial research-based evidence, while others are not. There is thus an urgent need for future well designed trials to address key clinical questions. (Less)

To the Editor: I read with interest the article by Wiland, et al 1 reporting on patients with early moderate to severe rheumatoid arthritis who achieved remission while receiving etanercept (ETN) 50 mg once weekly (QW) plus methotrexate (MTX). They experienced significant worsening in patient-reported outcome (PRO) measures when switched to placebo or …

Anti-drug antibodies (ADAbs) develop in up to a third of patients treated with biologic agents, with such immunogenicity being one of the main reasons for the loss of efficacy observed in an important proportion of patients treated with such agents. The appearance of ADAbs has consequences in terms of efficacy and tolerance of the biodrug: the development of ADAbs is associated with a poorer clinical response and with an increased risk of adverse effects. Formation of ADAbs has been observed with all biologic DMARDs, but anti-TNF agent mAbs appear to be the largest contributors, independent of humanization of the antibody. ADAb identification is technically difficult and not standardized, partly explaining important variations between published studies. A variety of factors can influence the risk of ADAb appearance, some of which are linked to the treatment strategy, such as the combination with synthetic DMARDs or the rhythm of administration of the biodrug, whereas other factors are dependent on the patient, such as the level of inflammation at onset or body weight. The detection of these antibodies and/or the dosage of the biologic agent itself could have consequences for the bedside practice of clinicians and should be well understood. This review of the literature proposes an overview of the data published on the subject to help clinicians manage the biodrugs according to these new concepts.

Resume Un groupe de travail du Comite directeur des essais therapeutiques de l’EULAR a determine, a partir des donnees etablies, des directives pour le traitement de la gonarthrose. Methodes. La premiere etape selectionnait les modalites therapeutiques a prendre en consideration. La deuxieme etape etait une recherche bibliographique concernant toutes les publications en langues europeennes. La qualite de chaque etude a ete notee. Lorsque cela etait possible, il a ete calcule pour chaque traitement etudie le nombre de patients a traiter pour en ameliorer un et l’importance de l’effet therapeutique. La troisieme etape a defini des recommandations de base ; ces definitions ont ete etablies par consensus d’experts, par votes successifs (approche Delphi ). L’etape finale a consiste a classer ces propositions selon les donnees scientifiques disponibles. Le groupe d’experts a egalement developpe une deuxieme serie de propositions relatives aux axes de recherche futurs. Resultats. Sept cent quarante-quatre etudes concernaient les traitements de la gonarthrose. L’analyse quantitative de l’effet therapeutique n’a ete possible que dans 61 etudes. Neanmoins, des recommandations pour la prise en charge de la gonarthrose reposant sur les donnees actuellement disponibles et l’avis des experts ont pu etre etablies, de meme que des propositions relatives aux axes de recherche futurs. Conclusion. Ces directives cliniques sur le traitement de la gonarthrose sont les premieres a combiner une approche fondee sur des donnees scientifiques et une approche consensuelle fondee sur l’avis d’experts, pour evaluer differentes modalites therapeutiques. Il apparait que seules certaines propositions sont corroborees par des donnees scientifiques etablies. Ce constat souligne le besoin urgent de conduire des essais bien concus afin d’obtenir des reponses a des questions cliniques majeures.

Resume Les methodes d’imputabilite visent a evaluer la probabilite qu’un ou plusieurs medicaments soient incrimines dans la survenue d’un evenement indesirable. Qu’elles soient « globales », a l’instar de celle proposee par l’OMS, ou « algorithmique », a l’image de la methode francaise, toutes s’appuient sur trois ordres de criteres : chronologiques, semiologiques et bibliographiques. Si ces methodes se caracterisent par leur grande sensibilite, elles manquent en revanche de specificite.

The objective was to investigate the presence of mycoplasmas in rheumatoid arthritis (RA) and other chronic arthritides. Samples of synovial fluid (SF) were systematically collected from all patients presenting with an articular effusion. Each sample was divided into three parts. The first was kept for cytological count and culture on standard media for pyogens and mycobacteria, the second was cultivated on specific media for mycoplasmas and the third frozen for subsequent study by polymerase chain reaction (PCR). A total of 209 samples were studied. Half of the patients had inflammatory rheumatic diseases: RA (27), spondyloarthropathy (28), connective tissue disease (5), unclassified arthritis (45). The remaining suffered from other conditions, including osteoarthritis (60), gouty arthritis (19), haemarthrosis (5), post-traumatic effusion (2). Eight samples were positive by culture, two for Mycoplasma horminis, three for M. fermentans, one for M. salivarium, one for M. orale and one for Ureaplasma urealyticum. All the patients concerned had an inflammatory rheumatic disease: five had RA, one had psoriatic arthritis and two had unclassified arthritis. These results were confirmed by PCR in two cases (one M. fermentans, one U. urealyticum). The lack of sensitivity of the conventional PCR assay on SF is discussed. Mycoplasmas were mainly detected in SF of RA patients. These results raise the question of the possible role of mycoplasmas in the triggering and maintenance of inflammatory rheumatic diseases, especially RA.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 20 novembre 2013

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 7 novembre 2012

Resume Les manifestations thrombotiques liees aux emboles de cristaux de cholesterol sont habituellement accompagnees de signes cutanes. Nous rapportons l’observation d’une myosite isolee du mollet chez un homme de 58 ans, originale par l’absence de manifestations dermatologiques specifiques. Le bilan etiologique s’est avere negatif. L’evolution etait spontanement favorable. Les signes cliniques des emboles de cristaux de cholesterol sont polymorphes. Classiquement, les atteintes cutanees, renales et ophtalmologiques figurent au premier plan. Des formes generalisees peuvent en imposer pour une pathologie systemique. Le diagnostic est histologique. La therapeutique est symptomatique, les anti-agregants plaquettaires sont discutes. Neanmoins le role aggravant des therapeutiques anticoagulantes est reconnu.

Objective To estimate the prevalence of fibromyalgia (FM) syndrome in the French general population. Methods A validated French version of the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) was administered via telephone to a representative community sample of 1014 subjects aged over 15 years, selected by the quota method. A positive screen was defined as: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and 2-fatigue criteria (LFESSQ-6). To estimate the positive predictive value of LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of rheumatology outpatients (n = 178), who were then examined by a trained rheumatologist to confirm or exclude the diagnosis of FM according to the 1990 American College of Rheumatology criteria. The prevalence of FM in the general population was estimated by applying the predictive positive value to eligible community subjects (i.e., positive screens). Results In the community sample, 9.8% and 5.0% screened positive for LFESSQ-4 and LFESSQ-6, respectively. Among rheumatology outpatients, 47.1% screened positive for LFESSQ-4 and 34.8% for LFESSQ-6 whereas 10.6% were confirmed FM cases. Based on positive screens for LFESSQ-4, the prevalence of FM was estimated at 2.2% (95% CI 1.3–3.1) in the French general population. The corresponding figure was 1.4 % (95% CI 0.7–2.1) if positive screens for LFESSQ-6 were considered. Conclusion Our findings suggest that FM is also a major cause of widespread pain in France since a point prevalence of 1.4% would translate in approximately 680,000 patients.

Although non-pharmacological interventions are the cornerstone of osteoarthritis management, analgesics are an important component of treatment during the symptomatic periods of the disease. In this respect, current practice guidelines advocate the use of a simple analgesic, acetaminophen, or a non-steroidal anti-inflammatory drug (NSAID), given either systemically or topically as first-line or second-line drug therapies. The present paper aims first to assess the evidence for the efficacy and safety of these medications. Given the increasing importance of patient involvement in decision-making, the following key practical issue regarding acetaminophen and NSAIDs will then be addressed: 'which drug do patients prefer?' Regarding NSAIDs, a further question concerns the place for non-selective agents and cyclo-oxygenase-2 (COX-2) selective inhibitors (coxibs) in the light of new warnings and contraindications concerning coxibs in patients with increased risk of cardiovascular thrombotic events.

Background Clinical trials performed in RA patients with anti-TNFa therapy lead to demonstrate the superiority of DMARDs association strategy over biologic monotherapy. Accordingly, the association Methotrexate-bioDMARD became the gold standard of biological treatment for RA patients. Nevertheless, various registries have shown that, in daily practice, most biologics are used as monotherapy in about 30% of RA patients. Thus, it seems to be important to improve our knowledge on the impact of the use of biological treatments as monotherapy. Objectives The aim of this study was to assess the maintenance rate and efficacy of Abatacept (ABA) in monotherapy compared to ABA + conventional synthetic DMARD (csDMARD) after 6 months (M6) in RA patients using data from the ORA registry. Methods Patients were recruited according inclusion criteria of ORA registry: adult patients affected by RA according to ACR 1987 criteria and treated with ABA. Exclusion criteria were missing data for therapeutic response or maintenance. The maintenance rate was analysed in two steps: 1) classical analysis of ABA maintenance rate, comparing the patient group in which ABA was initiated as monotherapy to the group in which ABA was initiated in combination with csDMARD; 2) Evaluation of the maintenance rate of therapeutic strategies: ABA monotherapy vs. ABA + csDMARD, any change of csDMARD treatment nature being considered as failure of retention. Efficacy of therapeutics was defined according to EULAR response criteria. Statistical analyses used Chi-2 test to compare the two groups of patients, or Fisher exact test if needed. A statistical threshold of 0.05 was chosen. Results The maintenance rate after 6 months of treatment was evaluated within 569 patients. No significant difference was found in ABA maintenance rate between ABA initiated as monotherapy and ABA + csDMARD (75% (142/188) vs. 76% (291/381) respectively, p=0.824). However, a significant difference was observed in maintenance rate of therapeutic strategy in ABA initiated as monotherapy compared to ABA + csDMARD (58.5% (110/188) vs. 68% (258/381) respectively, p=0.031). Among patients in whom ABA was initiated as monotherapy, a csDMARD was secondarily associated to ABA in 16.5% of patients within the first 6 months of treatment. Data on ABA efficacy were available for 444 patients. There was no significant difference of proportion of responders after a 6-months treatment between ABA monotherapy compared to ABA + csDMARD (60.2% (88/146) vs. 60% (179/298) respectively, p=0.967). Conclusions This work represents the first study comparing Abatacept monotherapy and ABA combined with csDMARD. Data from the French national registry ORA allowed to perform a “real-life” analysis relevant for bedside practice, even if radiological data are needed to evaluate structural modifications. ABA can be used as monotherapy with satisfactory effectiveness and maintenance, providing an acceptable alternative when csDMARDs are undesirable. Nonetheless, this treatment strategy exposes the rheumatologist to add a csDMARD in a high proportion of patients during the first 6 months. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2001

Background Both environmental or lifestyle factors, including smoking, overweight and periodontal disease, were found to be associated with an increased risk for developing rheumatoid arthritis (RA). Few studies suggested that blood transfusions (BT) could be another potential risk factor for RA. Although the underlying pathophysiological mechanism is unclear, it is well known that BT leads to significant modifications in recipient immune system. Objectives The aim of this study was to estimate the prevalence of BT history in a cohort of patients with early RA, and to compare the course of the disease between transfused and non-transfused RA patients in the cohort. Methods The ESPOIR cohort is a French national prospective cohort that included patients with early arthritis prone to develop into RA. History of BT before inclusion in the cohort was searched for each patient with a confirmed diagnosis of RA after five-year follow-up in the cohort. A standardized prevalence ratio (SPR) was determined to evaluate the over-risk of BT past history in RA patients compared to age and sex matched general population. Clinical characteristics of RA were compared at inclusion and after five years of follow-up between BT recipients and non-recipients. Results Among the 813 patients included in the cohort, 705 had a confirmed diagnosis of RA after five years of follow-up. Among assessable patients, 10.5% (72/686) had a past history of BT at inclusion in the cohort. For age and sex-matched general population, the prevalence of BT is about 0.3%, leading to a SPR of 35 (95%CI: 27.4 – 44). The median time between BT and onset of arthritis was 25.5 years (IQR: 16 – 33). Furthermore, patients with history of BT were preferentially ACPA-negative (75.0% [54/72] for BT recipients vs. 53.2% [327/614] for non-recipients; p

A task force for the EULAR standing committee for clinical trials determined the methodological and logistical approach required for the development of evidence-based guidelines for treatment of knee osteoarthirits (OA). Methods. The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the databases of all European-language publications. All of the relevant studies were quality scored. The third stage involved determination of key clinical propositions by expert consensus employing a Delphi approach. The final stage involved ranking of these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus. Results. Seven hundred and forty-four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. Conclusions. These are the first clinical guidelines on knee OA to combine an evidence-based approach and a consensus approach across a wide range of treatment modalities. It is apparent that only certain clinical propositions are supported by substantial research-based evidence. There is thus an urgent need for future well-designed trials to address key clinical questions.

This report describes the case of a patient with a 14-month course of severe oligoarthritis associated with acne. Pure cultures of Propionibacterium acnes were isolated from synovial tissue and synovial fluid specimens collected from the same joint after a 4-month interval. After 2 months of treatment with roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal antiinflammatory drug (NSAID), followed by 4 months of treatment with azithromycin 1 gm/week and an NSAID, the synovitis persisted. Cultures of skin lesions and synovial fluid at this time were negative. Although P acnes has previously been isolated from bone specimens obtained from patients with osteitis associated with acne, this is the first report of the isolation of this microorganism from the synovial tissue of a patient with arthritis associated with acne. Our findings raise the question of the role of P acnes in the pathogenesis of arthritis associated with acne.

OBJECTIVE--To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). METHODS--In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993. RESULTS--The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjogren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one. CONCLUSION--The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.