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Introduction: Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are 'paradoxical' when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF., Patients and Methods: In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients., Results: Between May 2013 and April 2014, 65 patients with Crohn's disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months-Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn's disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations., Conclusion: Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.

The use of TNFα antagonists must follow specific guidelines to ensure optimal effectiveness and safety. The French Society for Rheumatology (SFR) and Task Force on Inflammatory Joint Diseases (CRI), in partnership with several French learned societies, asked the French National Authority for Health (HAS) to develop and endorse good practice guidelines for the prescription and monitoring of TNFα antagonist therapy by physicians belonging to various specialties. These guidelines were developed, then, validated by two multidisciplinary panels of experts based on an exhaustive review of the recent literature and in compliance with the methodological rules set forth by the HAS. They pertain to the initial prescription of TNFα antagonists and to a variety of clinical situations that can arise during the follow-up of patients receiving TNFα antagonists (infections, malignancies, pregnancy, vaccination, paradoxical adverse events, surgery, use in older patients, and vasculitides)., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Some clinical pictures satisfy spondyloarthritis criteria without any detected imaging signs and the question sometimes arises in clinical daily practice if biologics should be started. Our aim was to evaluate anti-TNF efficacy in patients with clinical but not imaging (radiographic, CT-scan, MRI) signs of spondyloarthritis., Methods: This retrospective study concerned patients with axial spondyloarthritis fulfilling European Spondyloarthritis Study Group (ESSG) criteria, treated with anti-TNF after failure of conventional therapies. Therapeutic responses, rated according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)-50% or 20 mm and ASAS-20 or -40 definitions, were evaluated after 12 months. Factors associated with those responses were also sought. Propensity score was used to check thereafter whether there were interactions with some baseline variables., Results: Among 385 patients included, 257 with imaging signs had significantly more frequent therapeutic responses (P=0.0005). About 40% of the spondyloarthritis patients without imaging signs responded to anti-TNF. The response rate was significantly higher in HLA-B27 carriers with initial imaging signs (P=0.028). Furthermore, responders were younger at biotherapy onset, with lower Bath Ankylosing Spondylitis Functional Index (BASFI) and pain visual analog scale score, and higher C-reactive protein (CRP), compared to non-responders. After weighted calculation, the prediction of response to TNF-blockers was quite similar in both groups., Conclusion: The percentage of patients with exclusively clinical signs who responded to anti-TNF was far from negligible. Regardless the HLA-B27 status, having imaging signs of spondyloarthritis does not provide a superiority of response to anti-TNF compared to the absence of imaging sign. The absence of any imaging sign in patients with spondyloarthritis should therefore not lead to the exclusion of anti-TNF therapy., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To describe cases of new onset of inflammatory bowel disease (IBD) in patients with inflammatory rheumatic disease (IRD) receiving anti-TNF-α therapy., Methods: A call for observations of such cases was sent to members of the French "Club rhumatismes et inflammation". Only patients without intestinal symptoms before introduction of anti TNF-α agents were included., Results: During a 2-year period, 16 patients were declared: nine men and seven women, mean age 41.5 ± 17.4 years, 12 patients with ankylosing spondylitis, one with rheumatoid arthritis, one with psoriatic arthritis and two juvenile idiopathic arthritis with enthesitis related arthritis. Overall, 14 patients received etanercept and two had infliximab. The meantime frame between onsets of anti-TNF--α drugs and development of IBD was 29.3 ± 20.1 months. According to endoscopic and histological findings, IBD was classified as typical Crohn's disease in eight cases, Crohn's-like disease in six cases, indeterminate in one case and definite ulcerative colitis in one case. For all cases, each TNF-α blocking agent was discontinued and replaced by another monoclonal anti TNF-α antibody. After a mean follow up period of 23.4 ± 19.5 months, outcome was favorable without recurrent or flaring IBD., Conclusions: Paradoxical IBD may occur during anti TNF-α therapy for inflammatory rheumatic disease, mostly in patients with spondylarthropathies while receiving etanercept, at a frequency estimated to 0.15% in the French patients with spondylarthropathies exposed to TNF-α antagonists. The IBD mainly corresponded to Crohn's or Crohn's-like disease. On the contrary, new onset IBD is less frequently observed in other cases of IRD and with other TNF--α blockers., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease., Methods: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts., Results: Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information., Conclusion: These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objectives: Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific., Methods: Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated., Results: Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P = 0.303), the latter experiencing two psoriasis and three AAU., Conclusions: Undesirable side effects--IBD, AAU and psoriasis--may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

Objective: The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients., Methods: First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually., Results: ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics., Conclusion: This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.