BAFF serum levels in myasthenia gravis: effects of therapy

B-lymphocyte activating factor (BAFF) is a key survival factor for B lymphocytes. Myasthenia gravis (MG) is an antibody-mediated disease of neuromuscular transmission. Most MG patients have serum antibodies against the nicotinic acetylcholine receptor (AChR). Anti-AChR positive MG is associated with thymus alterations, such as follicular hyperplasia and thymoma. The aim of our study was to evaluate serum BAFF levels in MG patients in different phases of their disease and the effects of therapy. We tested serum samples from 66 MG patients. No patient had anti-muscle specific tyrosine kinase (MuSK) antibodies. BAFF levels were measured by quantitative ELISA. Mean serum BAFF levels were significantly higher in the MG population than in controls. We confirm previous observations that serum BAFF levels are increased in MG, although with no relation with disease severity. In MG patients under IS therapy BAFF mean level was significantly decreased in comparison with the untreated population and controls

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

OBJECTIVE: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. METHODS: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity. RESULTS: Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement. CONCLUSIONS: Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH

Correction to: Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation (Journal of Thrombosis and Thrombolysis, (2021), 52, 3, (772-778), 10.1007/s11239-021-02429-z)

none63In the original version of the article, the group was mentioned incorrectly. The correct name is "CSS COVID-19 Group". Also, in the Table 4 the p for ICU access and CKD were 0.024 (instead of 0.24) and 0.006 (instead of 0.06). These have been corrected with this erratum.noneGrandone E.; Tiscia G.; Pesavento R.; De Laurenzo A.; Ceccato D.; Sartori M.T.; Mirabella L.; Cinnella G.; Mastroianno M.; Dalfino L.; Colaizzo D.; Vettor R.; Intrieri M.; Ostuni A.; Margaglione M.; Alboini P.E.; Antonioni A.; Aucella F.; Bochicchio G.B.; Carbonelli C.; Carella M.; Castori M.; Centonze A.; Ciliberti G.; Copetti M.; Corritore M.; De Cosmo S.; D'Aloiso L.; D'Errico M.M.; de Matthaeis A.; Del Gaudio A.; Di Giorgio A.; Giambra V.; Greco A.; Florio L.; Fontana A.; Inchingolo V.; Inglese M.; Labonia M.; La Marca A.; Latiano T.; Leone M.; Maiello E.; Mangia A.; Marciano C.; Massa V.; Massafra S.; Orciulo G.; Palladino N.; Perna R.; Piscitelli P.; Piemontese M.; Prencipe M.A.; Raggi P.; Rodriquenz M.G.; Russo R.; Sancarlo D.; Simeone A.; Trischitta V.; Zarrelli M.; Vaira P.; Vergara D.; Vescovi A.Grandone, E.; Tiscia, G.; Pesavento, R.; De Laurenzo, A.; Ceccato, D.; Sartori, M. T.; Mirabella, L.; Cinnella, G.; Mastroianno, M.; Dalfino, L.; Colaizzo, D.; Vettor, R.; Intrieri, M.; Ostuni, A.; Margaglione, M.; Alboini, P. E.; Antonioni, A.; Aucella, F.; Bochicchio, G. B.; Carbonelli, C.; Carella, M.; Castori, M.; Centonze, A.; Ciliberti, G.; Copetti, M.; Corritore, M.; De Cosmo, S.; D'Aloiso, L.; D'Errico, M. M.; de Matthaeis, A.; Del Gaudio, A.; Di Giorgio, A.; Giambra, V.; Greco, A.; Florio, L.; Fontana, A.; Inchingolo, V.; Inglese, M.; Labonia, M.; La Marca, A.; Latiano, T.; Leone, M.; Maiello, E.; Mangia, A.; Marciano, C.; Massa, V.; Massafra, S.; Orciulo, G.; Palladino, N.; Perna, R.; Piscitelli, P.; Piemontese, M.; Prencipe, M. A.; Raggi, P.; Rodriquenz, M. G.; Russo, R.; Sancarlo, D.; Simeone, A.; Trischitta, V.; Zarrelli, M.; Vaira, P.; Vergara, D.; Vescovi, A