Background:
Alemtuzumab is a humanized monoclonal antibody directed at CD52 approved as a disease-modifying therapy for relapsing forms of multiple sclerosis (MS).
Objective:
To describe a case of a ...life-threatening autoimmune anemia occurring after a first course of alemtuzumab for relapsing-remitting MS in a 28-year-old male.
Methods:
Case report.
Results:
A 28-year-old male developed a life-threatening autoimmune anemia occurring 11 months after first alemtuzumab course.
Conclusion:
We report the third case of autoimmune hemolytic anemia following treatment with alemtuzumab in a young MS patient. Due to the severity of this adverse event, neurologists using this treatment should be alert.
Hereditary hemorrhagic telangiectasia (HHT) disease is a rare genetic disorder with symptoms and complications that can significantly affect patients' daily lives. To date, no scale has been ...validated to assess the specific symptoms of this disease on the quality of life (QOL) of HHT patients. This makes it difficult for clinicians to accurately measure the quality of life of patients with HHT. The present study aims to develop and validate a QOL measurement tool specific to HHT disease: the QOL questionnaire in HHT (QoL-HHT). A quantitative, non-interventional, multi-center study involving HHT patients in twenty French HHT expert centers was conducted. A calibration sample of 415 HHT patients and a validation sample of 228 HHT patients voluntarily participated in the study. Data were analyzed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), Exploratory Structural Equation Modeling (ESEM) analyses, reliability analyses, and correlational analyses. The EFA, CFA and ESEM results allowed us to provide evidence of the factorial structure of a questionnaire composed of 24 items measuring 6 domains of QOL: Physical limitations, social relationships, concern about bleeding, relationship with the medical profession, experience of symptoms, and concern about the evolution of the disease. Cronbach's alpha coefficients (> 0.70) demonstrated reliable internal consistency of all the QoL-HHT scores (dimensions). The results of the test-retest provided further evidence of the reliability of the QOL-HHT scores over time. Correlational analyses provided evidence for the convergent validity of the QoL-HHT scores. We developed a simple and quick self-assessment tool to measure quality of life specific to HHT disease. This study demonstrated reliability and validity of our QoL-HHT scores. It is a very promising tool to evaluate the impact of HHT disease on all aspects of the quality of life of HHT patients in order to offer them individualized medico-psycho-social support.
Background
The vascular endothelium is markedly disrupted in sickle cell disease (SCD) and is the converging cascade of the complex pathophysiologic processes linked to sickle cell vasculopathy. ...Circulating endothelial activation and/or apoptotic markers may reflect this endothelial activation/damage that contributes to the pathophysiology of the SCD vascular complications.
Methods
Plasmatic levels of circulating endothelial cells (CECs), E‐selectin, progenitor's endothelial cells (EPCs), and circulating extracellular vesicles (EVs) were evaluated in 50 SCD patients, 16 with vasculopathy. The association between these markers and the occurrence of disease‐related microvascular injuries of the eye (retinopathy), kidney (nephropathy), and skin (chronic active ulcers) was explored.
Results
Among the endothelial activation markers studied, only higher plasma levels of E‐selectin were found in SCD patients with vasculopathy (p = .015). Increased E‐selectin levels were associated with retinopathy (p < .001) but not with nephropathy or leg ulcers. All patients, at steady state, with or without vasculopathy, did not display a high count of CEC and EPC, markers of endothelial injury and repair. We did not show any significant differences in EVs levels between vasculopathy and not vasculopathy SCD patients.
Conclusions
Further studies will be required to determine whether the E‐selectin could be used as an early biomarker of retinopathy sickle cell development.
Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus ...anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra.
Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation.
Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4%
31.2%, p = 0.76), the in-hospital mortality (31.7%
33.0%, p = 0.83), the high-flow oxygen requirement (17.5%
18.3%, p = 0.86), the intensive care unit admission rate (30.8%
22.2%, p = 0.30), and the mechanical ventilation rate (15.4%
11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1%
30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1%
21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3%
9.2%, p = 0.44).
Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.
•Inflammatory myopathies (IM) are rarely associated to myelodysplastic syndromes (MDS).•Dermatomyositis and anti-TIF1g + are the most frequent forms of IM associated to MDS.•Antisynthetase syndrome ...is not observed in MDS patients.•Association with MDS has a negative impact on IM patients’ survival.
Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS.
We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS.
Median age of patients at IM diagnosis was 66 years (range 26 – 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS−), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002).
IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS.
It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.
Primary endpoint ...was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.
Retrospective multicenter study in French national HHT Registry patients exposed to AT.
We included 126 patients with 180 courses of AT. Median follow-up was 24 11–52 months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 1.12;4.87, p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 1.93;6.66, p < 0.001) or transfusion (HR 3.15 1.61;6.18, p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 1.57;4.65, p < 0.001) or MBE (HR 4.62 2.68;7.98, p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 1.37;11.22, p = 0.011).
Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.
•Similar tolerability of antiplatelet and anticoagulant therapies in HHT•Dual antiplatelet therapy is not tolerated in HHT and should be avoided•Risk factors in HHT patients for major bleeding events (MBE) occurrence or premature discontinuation under antithrombotics are ≥60 years old, previous history of MBE or gastrointestinal bleeding, hospitalizations for bleeding in the last 3 months to help guide clinicians prescribing antithrombotic medication•Direct oral anticoagulants, notably apixaban, appear well tolerated by HHT patients
Abstract
Objective
To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK).
Methods
A total of 209 patients with TAK median age 29 years ...(interquartile range 7–62), 186 (89%) females were included. They received either TNF-α antagonists n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5) or tocilizumab n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively.
Results
A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years odds ratio 2.09 (95% CI 1.09, 3.99) was associated with complete response, whereas vascular signs OR 0.26 (95% CI 0.1, 0.65), baseline prednisone ≥20 mg/day OR 0.51 (95% CI 0.28, 0.93) were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively and systemic signs at baseline HR 2.01 (95% CI 1.30, 3.11) were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies 37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively.
Conclusion
This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.
Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test ...how IFN signatures were associated with HRQOL in SLE patients.
Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores.
A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038).
This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients.
