Charlotte Hua

Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis.

To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines.

2016 update of the EULAR recommendations for the management of early arthritis

Objectives Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. Methods In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. Results The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. Conclusions These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.

Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis

Objective Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has been shown to improve survival rates in other inflammatory diseases. We aimed to assess the available literature on the cardiovascular impact of HCQ in patients with RA. Methods We systematically searched for studies evaluating the effects of HCQ on cardiovascular outcomes of known risk factors for CVD in patients with RA. Databases searched were MEDLINE (via PubMed), EMBase, Cochrane Library and the American College of Rheumatology and European League Against Rheumatism annual meetings. A meta-analysis was performed with a random-effects model, estimating mean differences (MDs), HRs and 95% CIs. Data were extracted by one investigator and independently checked by another. Results The literature search revealed 185 articles and abstracts of interest; further examination resulted in 16 studies fulfilling the criteria. The MDs between HCQ users and non-users in levels of total, low-density and high-density cholesterol and triglycerides were −9.8 (95% CI −14.0 to −5.6), −10.6 (95% CI −14.2 to −7.0), +4.1 (95% CI 2.2 to 6.0) and −19.2 (95% CI −27.2 to −11.1), respectively. Diabetes incidence was lower for HCQ ever users than never users (HR 0.59 (95% CI 0.49 to 0.70)). HCQ seemed to decrease insulin resistance and incidence of CVD, but data were too few for meta-analysis. Conclusion Besides its limited efficacy for disease activity and progression, HCQ may benefit the metabolic profile and to a lesser extent cardiovascular events in patients with RA, which suggests its usefulness combined with other conventional synthetic disease-modifying antirheumatic drugs.

Diagnosis, prognosis and classification of early arthritis: results of a systematic review informing the 2016 update of the EULAR recommendations for the management of early arthritis

Objective To update the evidence pertaining to the diagnosis, prognosis and classification of patients with early arthritis (EA), and to inform the 2016 European League Against Rheumatism (EULAR) recommendations for the management of patients with EA. Methods MEDLINE, EMBASE and Cochrane databases were searched up to October 2015. The first part of the systematic literature review (SLR) involved a search for studies investigating the recognition and referral of EA. The second part involved a search for studies to identify the place of laboratory and imaging tests in establishing a diagnosis and a prognosis in patients with EA. Results Regarding the issue of referral of patients with EA (1643 hits), 4 studies were included. These studies were in support of early referral for patients with EA. Regarding the issue of diagnosis and prognosis of patients with EA (11 435 hits), 88 studies were included, evaluating mainly the value of rheumatoid factor (RF) and anticitrullinated-peptide antibodies (ACPAs). Sensitivity of these antibodies for a RA diagnosis in patients with EA was moderate (40–80%). Specificity was higher, notably for ACPAs (frequently >80%). ACPAs also showed better prognostic performance than RF (negative predictive values around 80%). We confirmed that structural damage on baseline X-rays is predictive of further radiographic progression in patients with EA. Regarding other imaging modalities, data are sparse. Conclusions This SLR highlights the importance of early referral for patients with EA and confirms that RF and mainly ACPAs as well as a search for structural X-rays changes may help in the diagnosis and prognosis of patients with EA.

Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis

Objective To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). Methods The expert committee defined research questions concerning non-pharmacological interventions, patient information and education, non-steroidal anti-inflammatory drug, glucocorticoid (GC) and disease-modifying antirheumatic drugs (DMARDs) use, as well as on disease monitoring. The SLR included articles published after the last EULAR SLR until November 2015 found in the MEDLINE, EMBASE and Cochrane databases and abstracts from the 2014 and 2015 American College of Rheumatology and EULAR conferences. Results Exercise programmes may improve pain and physical function in patients with EA. Patients with EA treated within the first 3 months of symptoms have better clinical and radiological outcomes than those treated beyond 3 months. The clinical and radiological efficacy of GCs is confirmed, with similar efficacy of oral and parenteral administrations. Long-term data raise concerns regarding cardiovascular safety when using GCs. Step-up DMARD therapy is as effective as intensive DMARD therapy ‘ab initio’ for the long-term outcome of EA. Short-term superiority of intensive therapy with bDMARDs is not maintained on withdrawal of bDMARD. Patients with early psoriatic arthritis have better skin and joint outcomes when tight control is used compared to standard care. Conclusions The findings confirm the beneficial effect of exercise programmes and the importance of early drug therapy and tight control. They support the use of methotrexate and GCs as first-line drugs, although the long-term use of GCs raises safety concerns.

Phosphatidylserine Outer Layer Translocation Is Implicated in IL-10 Secretion by Human Regulatory B Cells

B cells can have a regulatory role, mainly mediated by interleukin 10 (IL-10). IL-10 producing B cells (B10 cells) cells remain to be better characterized. Annexin V binds phosphatidylserine (PS), which is externalized during apoptosis. Previous works suggested that B10 cells are apoptotic cells since they bind Annexin V. Others showed that Annexin V binding could also be expressed on viable B cells. We aimed to explore if PS exposure can be a marker of B10 cells and if PS exposure has a functional role on B cell IL-10 production in healthy subjects. We found that B10 cells were significantly more often Annexin V+ than IL-10 non-producing B cells. After CpG activation, Annexin V+ B cells differentiated more often into B10 cells than Annexin Vneg B cells. Cell death and early apoptosis were similar between Annexin V+ and Annexin Vneg B cells. PS blockage, using biotinylated AnV and glyburide, decreased B10 cell differentiation. This study showed that B10 cells have an increased PS exposure independently of any apoptotic state. B cells exposing PS differentiate more into B10 cells whereas PS blockage inhibits B10 cells generation. These results strongly suggest a link between PS exposure and B10 cells.

Response to: ‘Metabolic and cardiovascular benefits of hydroxychloroquine: exploration in a wider population at high CV risk’ by Pareek et al

In their letter to the editor, Pareek et al raised some issues regarding our recent paper.1 2 We appreciate their interest in our study and their positive comments. Pareek et al highlight the fact that several studies addressing the metabolic effect of hydroxychloroquine (HCQ) have not been included in our meta-analysis due to our stringent inclusion criteria (HCQ users vs non-users in patients with rheumatoid arthritis (RA)). We acknowledge …

Update of French Society for Rheumatology Recommendations for Managing Rheumatoid Arthritis

The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and non-pharmacological treatments. The recommendations deal with the diagnostic strategy for RA, treatment targets, management organization, drug selection based on the treatment line and prognostic factors, management of remissions, and global patient management. Disease-modifying anti-rheumatic drug (DMARD) therapy should be started as early as possible. Validated composite scores should be determined at regular intervals to assess disease activity - according to the tight disease control concept - to achieve the treatment target, i.e., a remission. Methotrexate is the recommended first-line DMARD. The treatment should be optimized when methotrexate is poorly tolerated or inadequately effective. While waiting for conventional synthetic DMARDs to take effect, glucocorticoid therapy can be used, for a brief period to keep the cumulative dose low. When a sustained remission without structural progression is achieved in a patient who is not taking glucocorticoid therapy, targeted therapy de-escalation according to tight disease control principles should be considered. Patients should be periodically screened for comorbidities and their risk factors, which should be evaluated and treated.

Response to eLetter: ‘Cardiovascular effects of hydroxychloroquine: a systematic review and meta-analysis’ by Mathieu et al

In their letter to the editor, Mathieu1 and colleagues provide information that reinforce the conclusions of our recent paper.2 3 We appreciate their interest in our study and complement the authors for their systematic review and meta-analysis of cardiovascular (CV) effects of hydroxychloroquine (HCQ) in rheumatoid arthritis (RA), lupus and other diseases. In our study, we have chosen to focus only on RA for homogeneity reasons and because we think that demonstration of a positive influence of …

OP0114 A Proliferative Inducing Ligand (April) Promotes IL-10 Production by Human B Cells

Background B cells may have a negative regulatory role, mainly mediated by interleukin 10 (IL-10). We recently showed that regulatory B cell functions are impaired in patients with rheumatoid arthritis (RA) and that a proliferation inducing ligand (APRIL) transgenic mice are protected against collagen induced arthritis. Objectives We aimed to explore the effect of APRIL on normal human B cell IL-10 production. Methods CpG induced IL-10 B cell production was compared in presence or absence of APRIL and B lymphocyte stimulating factor (BLys). The expression of the BLyS and APRIL receptor transmembrane activator and CAML interactor (TACI) and of BLyS specific receptor (BAFF-R) was compared between IL-10 producing and non-producing B cells. The effect of APRIL stimulated B cells on T cell cytokine production was analyzed after 3 days of co-culture. Signaling pathways of B cells activated by CpG and APRIL were analyzed by western blot. Similar experiments were performed on cells of RA patients. Results APRIL but not BLyS promotes IL-10 production by B cells (9.5 [6.8-13.2] vs 6.2 [3.9-7.0] vs 4.2 [3.3-8.0] % for APRIL, BLyS and culture medium alone respectively, APRIL vs media p=0.002 and APRIL vs BLyS p=0.007).The effect was abrogated by co-culturing of TACI-Fc. IL-10 producing B cells expressed significantly more TACI (7.1 [5.5-16.8] vs 2.4 [1.9-7.8]%; p=0.016) and less BAFF-R (2.3 [2.0-2.5] vs 2.7 [2.3-2.8] of mean fluorescence intensity; p=0.021) than non- IL-10 producing B cells. APRIL stimulated B cells decreased TNF-α (-36±13%, p=0.02) and IFN-γ (-14±3%; p=0.02) secretion of T cells compared to non-stimulated B cells but not IL-17 production (-14±14%, p=0.31). APRIL further stimulated CpG activated STAT3, ERK and JNK pathways. APRIL also promoted IL-10 production of B cells in RA patients and similar pattern of APRIL and BLyS receptors on IL-10 producing B cells were observed in RA patients and in controls. Conclusions We show for the first time that APRIL but not BLyS promotes IL-10 production by B cells and enhances the regulatory role of B cells on T cells by decreasing TNF-a and IFN-g by T cells. IL-10 producing B cells of RA patients are responsive to APRIL suggesting a possible therapeutic application by expanding B10 cells of these patients. Disclosure of Interest None declared