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To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0-100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with < 5% missing data. Internal validity coefficient was 0.90. Mean (standard deviation) long-form score was 72.8 ± 17.8, with lower scores in comorbidity and self-care and higher scores in adaptive skills. Reproducibility was good (0.86 [0.80; 0.92]). RAKE score was positively correlated with the patients' level of education and the HPs' opinion on the patients' knowledge. RAKE score showed good sensitivity to change: 66.8 ± 16.4 then 83.8 ± 12.7, representing a hedges effect size of 1.14 [95% CI 0.73; 1.55]. RAKE is an updated questionnaire assessing essential knowledge for patients with RA to enhance self-management according to current guidelines and the patients' perspective. RAKE can usefully inform patient education interventions, routine care and research., (© 2022. The Author(s).)

Objective: To evaluate the effect of a nurse-led patient education on safety skills of patients with inflammatory arthritis treated with biologic disease-modifying antirheumatic drugs (bDMARDs)., Methods: This is a multicentre, open-labelled, randomised controlled trial comparing an intervention group (face-to-face education by a nurse at baseline and 3 months later) with a control group (usual care) at the introduction of a first subcutaneous bDMARD. The primary outcome was score on the BioSecure questionnaire at 6 months (0-100 scale), a validated questionnaire assessing competencies in dealing with fever, infections, vaccination and daily situations. The secondary outcomes were disease activity, coping, psychological well-being, beliefs about medication, self-efficacy and severe infection rate., Results: 129 patients with rheumatoid arthritis and spondyloarthritis were enrolled in nine rheumatology departments; 122 completed the study; 127 were analysed; and 64 received the intervention (mean duration: 65 min at baseline and 44 min at 3 months). The primary outcome was met: the BioSecure score was 81.2±13.1 and 75.6±13.0 in the education and usual care groups (difference: +6.2, 95% CI 1.3 to 11.1, p=0.015), demonstrating higher safety skills in the education group. Exploratory analyses showed better skills regarding infections, greater willingness for vaccinations and greater adherence-related behaviours in the education group. Coping was significantly more improved by education; other secondary outcomes were improved in both groups, with no difference., Conclusions: Educating patients was effective in promoting patient behaviours for preventing adverse events with bDMARDs. An education session delivered to patients starting a first bDMARD can be useful to help them self-manage safety issues., Trial Registration Number: NCT02855320., Competing Interests: Competing interests: CB reports research grants from BMS, Fresenius Kabi, Lilly and Mylan, and was an occasional speaker for BMS, AbbVie, MSD, Mylan, Pfizer, Roche, Sanofi and UCB. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz and Sanofi, and consulting fees from AbbVie, Amgen, BMS, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB. CSo reports occasional consulting fees from AbbVie, UCB, Lilly, Nordic, GSK, Roche Chugaï and BMS., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence., Methods: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma., Results: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma., Conclusion: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA., Competing Interests: Competing interests: PD: participation to clinical trials and punctual interventions for BMS and Roche. CM: reports outside the submitted work personal fees from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Sanofi. PG: honoraria from AbbVie, Amgen, Biogaran, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, MEDAC, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. BF: research grants from AbbVie, Lilly, MSD and Pfizer, and honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, SanofiAventis, SOBI, UCB. PP: participation in clinical trials and punctual honoraria from MSD Pfizer ABBvie Sanofi Novartis Sandoz. BC: honoraria from AbbVie, BMS, Gilead, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, RocheChugai and research grants from Novartis, Pfizer, and Roche. GN: received honorarium from Novartis, Lilly and UCB. RS: received honorarium from Pfizer, BMS and UCB. XM: received honorarium from BMS, Gilead, Pfizer, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Information and education are recommended for patients with inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA). However, there is no consensus on which knowledge is essential to enhance patients' self-management. The aim of this study was to determine such knowledge., Methods: Based on published knowledge questionnaires (KQs) collected by a systematic literature review, a list of items was elaborated, classified in domains and sub domains. A Delphi process was performed with rheumatologists, healthcare professionals and patients in 2014-2015, selecting the items considered useful., Results: Three published KQs were analysed: 2 for RA; 1 for SpA and 5 unpublished KQs were collected. In the KQs, 90 knowledge items were mentioned for RA and 67 for SpA. The 1 st Delphi round enlarged the list to 322 items for RA and 265 items for SpA. The second round selected 69 and 59 knowledge items for RA and SpA respectively, of which 36 (52%) and 34 (57%) were not present or modified from the published KQs. Key domains included treatment strategies, managing cDMARDs and bDMARDs, managing symptomatic medications. Knowledge on non-pharmacological treatment concerned pain and fatigue, physical activity, adaptative skills to personal and professional environment, patient-HP communication and shared decision-making., Conclusion: The present study provides a corpus of knowledge considered essential for patients in the self-management of their arthritis. The selection of many items reflects recent emphasis on professional recommendations and the patients' perspective. Future work should lead to the development of new updated KQs for patients with inflammatory arthritis., (Copyright © 2019. Published by Elsevier Masson SAS.)

Objective: To assess the patients' information about biosimilars and to identify the patients' incentives and deterrents to concur with the use of biosimilars., Methods: Nation-wide cross-sectional study assessing information and concerns about biosimilars of French patients treated for rheumatic inflammatory diseases, whether they were treated or not by a biological DMARD. The assessment was available online from March to July 2017., Results: Among the 629 respondents, 43% knew what biosimilars were. The main sources of information were rheumatologists and patient associations. Among patients treated with a biosimilar, 44% were not informed before they received the treatment. The patients' concerns focused on the non-similar molecular structure (46%), efficacy (60%) and safety (57%) comparatively to the originator biologic. 15% of respondents would refuse to switch their biologic to its biosimilar. More than 50% of respondents would warily accept to switch medications and interrupt the treatment if in doubt. Being informed about biosimilars and a good understanding of the definition of biosimilars were characteristics associated with better adherence to biosimilars. The rheumatologist was considered the most influent source of information about biosimilars and was considered reliable when deciding to switch a biologic to its biosimilar. Patient were reluctant to substitution of the medications by pharmacists (2%). Medico-economical issues acted as an incentive and a deterrent to accept the switch of medication., Conclusion: Biosimilars are largely unknown to patients. Information seems to be instrumental in improving the patients' adherence to biosimilars and could help preserving the therapeutic relationship and avoiding a nocebo effect., (Copyright © 2019 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background/purpose: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling., Methods: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data., Results: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most., Conclusions: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA., Trial Registration Number: NCT01315652., Competing Interests: Competing interests: None declared.

The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objectives: Rheumatoid arthritis (RA) may have consequences on sexual life. The objective was to develop and validate a questionnaire assessing the impact of RA on sexuality., Methods: First, 6 patients (5 women, 1 man) with RA, 2 rheumatologists and 1 sexologist elaborated during a one-day focus-group type meeting an exhaustive list of issues relating to impact of RA on sexuality. The list was reduced by merging similar issues, then according to the relative importance for patients of each issue. A questionnaire was developed with input from these patients, with particular attention on phrasing. Psychometric properties (missing data, correlations with other disease aspects, reliability) were assessed in a multi-centre study., Results: The list of 33 issues related to impact of RA on sexuality included psychological issues (9), couple/relationship issues (9), physical issues (7), and general aspects (5). A 10-question numeric rating scale questionnaire was constructed. Preliminary validation was obtained on 53 patients (44 women, mean age 50.7 years; mean disease duration 14.4 years). The mean score was 3.3±2.5, missing data were acceptable (13%). Qualisex results were correlated with disease activity and symptoms (r=0.50-0.65, p< 0.001); but not with demographics, depression or coping. Qualisex was reliable in 40 patients: the intra-class correlation coefficient was 0.83 (95% CI: 0.70-0.91)., Conclusions: A simple (10 questions) and valid tool investigating impact of RA on sexuality has been developed with the involvement of patients. This tool can be useful to assess this important aspect of quality of life.

Multicentric reticulohistiocytosis is a rare, systemic, reactive histiocytic disease of unknown aetiology. Autoimmune diseases have previously been reported in association with multicentric reticulohistiocytosis, but whether this is a true association or mere coincidence is not known. Here, we report the case of a 50-year-old woman who had been diagnosed as suffering from rheumatoid arthritis (RA), four years ago with positive rheumatoid serology was evaluated for multiple asymptotic papulonodules eruption. Histopathologic examination was suggestive of multicentric reticulohistiocytosis. She developed concomitantly Sjogren syndrome with systemic manifestations. Multicentric reticulohistiocytosis may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis. The possibility of commune etiopathogeny of these affections is discussed., (Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To report our experience with rituximab therapy in patients with rheumatoid arthritis (RA) and a history of severe or recurrent bacterial infections., Patients and Methods: Retrospective observational study in five rheumatology departments experienced in the use of biotherapies. Patients were included if they had RA and a history of severe or recurrent bacterial infection (requiring admission and/or intravenous antimicrobial therapy) that contraindicated the introduction or continuation of TNFalpha antagonist therapy., Results: Of 161 RA patients given rituximab in the five study centers, 30 met the inclusion criteria, 23 females and seven males with a mean age of 58.4+/-11.8 years and a mean disease duration of 11.4+/-13.9 years. Among them, 22 had rheumatoid factors and 21 had received TNFalpha antagonist therapy (one agent in 15 patients, two in five patients and three in one patient). Prior infections were as follows: septicemia, n=2; lower respiratory tract infection or lung abscess, n=12; prosthesis infection, n=3; septic arthritis, n=3; endocarditis, n=1; pyelonephritis, n=2; osteitis, n=4; and various skin infections (erysipelas, cellulitis or skin abscess), n=6. Of these 33 infections, 21 occurred during TNFalpha antagonist therapy. During rituximab therapy, all patients received concomitant glucocorticoid therapy (mean dosage, 12+/-7.9 mg/day). The number of rituximab cycles was one in 13 patients, two in seven patients and three or more in 10 patients. Mean time from the single or last serious infection and the first rituximab infusion was 20.1+/-18.7 months. Mean follow-up since the first rituximab infusion was 19.3+/-7.4 months. During follow-up, six (20%) patients experienced one infection each. Immunoglobulin levels after rituximab therapy were within the normal range., Conclusion: Rituximab therapy was well tolerated in 24 (80%) of 30 patients with RA and a history of severe or recurrent bacterial infection. In everyday practice, rituximab therapy seems safe with regard to the recurrence of infectious episodes. However, longer follow-ups are needed., (Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

New treatment strategies require that rheumatoid arthritis (RA) be diagnosed as early as possible. New diagnostic markers were required, because rheumatoid factors (RF), until now criteria for classification of RA, are not sufficiently specific and sometimes appear late, thereby limiting their diagnostic usefulness. The objective of this review is to describe the current state of knowledge and more particularly to analyze the interest of new RA autoanti-bodies, called anti-peptide or anti-citrullinated protein anti-bodies (ACPA). Other autoanti-bodies have been described, including anti-Sa, anti-alpha enolase, and anti-calpastatin autoanti-bodies. Nonetheless, their diagnostic value remains limited compared to ACPA. Accordingly, in daily practice today, the only autoanti-bodies that must be tested for to diagnose RA are the ACPAs and RFs. The discovery of ACPA (initially called anti-keratin and anti-perinuclear anti-bodies) was a major step forward for the laboratory diagnosis of RA. The tests most often used routinely areenzyme-linked immunosorbent assays(ELISA) with cyclic citrullinated peptides, whence the name anti-CCP autoanti-bodies. Accordingly, the two terms ACPA and anti-CCP can both be used. The diagnostic value, in particular their specificity, is on the order of 95%, regardless of the method of identification. These markers are very useful and are often present earlier than RF. These ACPA also have prognostic value because they are associated with more aggressive forms of RA. On the other hand, their value over time, in particular, their fluctuation as a function of treatment, is more controversial. In practice, it is recommended to test for both RF and ACPA in a diagnostic work-up for early RA. During follow-up, the value of testing for these autoanti-bodies has not been demonstrated, but additional studies are still necessary with the anti-CCP autoanti-bodies and the new anti-citrullinated protein autoanti-bodies.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.

Objective: To date, only a few series of patients with paraneoplastic arthritis have been published. The charts of patients with cancer-associated arthritis were collected in order to describe characteristics of this rheumatism., Methods: A questionnaire was created for this study and validated by experts based on specific criteria of inclusion and exclusion. Histology of neoplasia was included., Results: In all, 16 males and 10 females with a mean (range) age of 57.5 years (28-85) were recruited from 17 nationwide centres in France. Patients presented with symmetric polyarthritis involving wrists and hands (85%) and extra-articular symptoms were frequent (84%). There was no specific biologic or radiographic feature. The mean (range) delay between the diagnosis of rheumatism and neoplasia was 3.6 months (0-21.2). Tumours were usually diagnosed after articular symptoms occurred (88.5%). Twenty patients had a solid cancer, and six a haematological malignancy. Adenocarcinoma of the lungs was the most frequent type of solid cancer (60%). Tumours were diagnosed at an early stage, which may explain the good median survival of 1.21 years (range 0.64-present) with a mean follow-up of 1.9 years (range 0.16-10). The percentage of articular symptoms resolution was significantly higher in patients with solid tumours, as compared to patients with haemopathy (p = 0.007). In cases of tumour relapse, rheumatic symptoms did not recur for 75% of patients., Conclusions: Underlying neoplasia should be considered in male patients with new onset polyarthritis, smokers, and particularly in patients chronically ill. Additional investigations should then be performed to diagnose cancer at an early stage.

Background: B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases., Objective: To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS)., Patients and Methods: Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay., Results: Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda)., Conclusion: FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.

Rheumatoid arthritis is a common and severe inflammatory rheumatic disease, for which the immune mechanisms are being decoded little by little. The pathogenic ncludes significant cellular actors of innate immunity (fibroblastic synoviocytes, macrophages, mastocytes...) and adaptive immunity (T and B lymphocytes). These actors interact through the production of and response to specific (cytokines, chemokines and auto-antibodies) and non-specific (prostaglandins, nitrous oxide [NO], complement, proteases) mediators. The chronology of this rheumatoid synovitis is becoming progressively clearer. Its initiation could be the consequence of a precocious activation of the innate immunity, induced by bacterial agents or debris (PAMP). The activation of the synoviocytes and the macrophages via specific receptors (PPR) unleashes an intense inflammatory reaction that triggers a cascade of events. The ongoing nature of this synovitis leads to the intra-articular recruitment of different cells of immunity. This cellular afflux amplifies the macrophagic and synoviocytic activation and proliferation. All of these interactive phenomena end in the production of large quantities of pro-inflammatory cytokines (TNFa, IL1, IL6, IL15, IL17, IL18) but also other pathogenic mediators (auto-antibodies, complement, prostaglandins, nitrous oxide...). This synovitis persists, as it is no longer regulated by a sufficient production of physiological regulators (soluble receptors and inhibitors of cytokines). The consequence of this intense inflammation and synovial proliferation leads to osteo-articular destruction by the production of proteases and the activation of osteoclasts by the RANK/RANK-ligand pathway under the effect of cytokines (TNFa, IL5, IL1, IL6, IL17) and other mediators (prostaglandins) liberated by synoviocytes, macrophages and lymphocytes. The decryption of this puzzle has already created new therapeutic orientations. The identification of new targets is one of the major consequences of this progress in immuno-rheumatology.