Body mass index influences the response to infliximab in ankylosing spondylitis

INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response

The Time to Offer Treatments for COVID-19

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Syndrome de Gougerot-Sjögren à expression systématique

Le syndrome de Gougerot-Sjögren (SGS) est un tarissement des sécrétions lacrymales et salivaires par exocrinopathie auto-immune. Il est primitif (SGSp) si il n'est pas associé à une autre connectivite. L'apparition d'atteintes extra-glandulaires pose un rpoblème de diagnostic différentiel. quand une telle atteinte précède le ss, la difficulté est de rattacher cette atteinte au SGS, en excluant une autre connectivite. Dans notre étude rétrospective, le but était de comparer deux groupes de patients, l'un ayant révélé le SGSp par atteinte extra-glandulaire et l'autre ayant vu apparaître une telle atteinte après le ss.Néanmoins , il ressort de nos observation que : les atteintes systématiques du SGSp sont rares, surtout si l'on exclut les atteintes auto-immunes spécifiques d'organes telles que les hépatites et les thyroïdites, et le principal diagnotic différentiel reste le LES " incomplets ". Les atteintes systématiques observées n'avaient pas de caractère de gravité particulier et les Ac anti-SSB étaient plus fréquents dans le groupe ayant une manifestation systématique inaugurale. Le problème central reste celui de la définition même du SGSp systematique qui est un diagnostic d'exclusion. Des études prospectives sont nécéssaires pour définir de tels critères.PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium ( Cutibacterium ) acnes

International audienceOvert infection by Propionibacterium acnes is lacking in many SAPHO syndromes, and antibiotics have only a transient and incomplete effect, either in SAPHO syndrome or acne. As several auto-inflammatory bone disorders sharing overproduction of IL-1β can mimic SAPHO, this syndrome could partly depend on genetically encoded overproduction of IL-1β. However, cyclic intracellular infections, mostly by P. acnes, can contribute to the enhanced IL-1β release by some skin cells, and probably by bone cells. P. acnes is indeed a powerful trigger of NLRP3-inflammasome activation and IL-1β, leading to osteitis and enhanced mesenchymal cells differentiation in osteoblasts. Recent advances in the understanding of acne suggest that first steps of this disorder are not driven by P. acnes, but by a relative deficiency of FoxO1 within the nucleus of sebaceous cells. A similar defect of FoXO1 in bone cells should also be sought in SAPHO, since repression of FoxO1 gene is found in lesional psoriasis skin, and is associated with an increased number of osteoblasts and high bone mass in mice. FoxO1 selectively promotes IL-1β production, so that its downregulation could help some P. acnes t escape innate immunity and persist in a latent state in bone cells, including mesenchymal stem cells. However, P. acnes itself possibly contributes to FoxO1 downregulation, like H. pylori infection which induces nuclear inactivation of FoxO1 in human gastric cells to slow down autophagic clearance. As bisphosphonates, which often improve SAPHO syndromes, enhance autophagy, it may be worth testing whether their combination with antibiotics is synergistic in SAPHO syndromes

Systemic lupus erythematosus with optical neuromyelitis (Devic's syndrome): A case with a 35-year follow-up

Optical neuromyelitis or Devic's syndrome is a very uncommon neurological manifestation of systemic lupus erythematosus. It is also associated with antiphospholipid antibodies, limited responsiveness to glucocorticoid treatment and a poor prognosis. We report the case of a female systemic lupus erythematosus patient who developed recurrent flares of optical neuritis and transverse myelitis. These flares consistently responded to glucocorticoid therapy. Despite the absence of overt anticardiolipin antibodies in the course of the disease, long-term anticoagulant therapy has been introduced with positive results. Treatments are usually of limited efficacy in Devic's syndrome. In our patient, however, aggressive glucocorticoid treatment resulted in prolonged survival.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Spondylitis Due to Mycobacterium xenopi in a Human Immunodeficiency Virus Type 1-Infected Patient: Case Report and Review of the Literature

Nontuberculous mycobacterial infections are well known to occur in patients with human immunodeficiency virus infection. However, spondylitis due to mycobacteria other than Mycobacterium tuberculosis is uncommon. We report a case of biopsy- and culture-proven Mycobacterium xenopi spondylitis in an AIDS patient and discuss approaches to diagnosis and therapy. This case serves to highlight the potential pathogenic role of this usually environmental commensal organism in severely immunosuppressed AIDS patients and uncertainties in their management, given the scarce data on appropriate therapy for this organism