Background:Dermatomyositis (DM) is a rare chronic systemic autoimmune disease with characteristic skin rash and progressive proximal muscle weakness. Current therapies encompass corticosteroids and other immunosuppressants and intravenous immunoglobulins (IVIg), however, none of these therapies are proven by randomized controlled phase 3 studies. There have been no large randomized clinical trials supporting the efficacy and safety of IVIg in DM.Objectives:The ProDERM study aimed to evaluate the efficacy and safety/tolerability of IVIg in DM patients in a double-blind, randomized, placebo-controlled, international multi-center, phase III clinical trial.Methods:The trial consisted of a double-blind, placebo-controlled First Period (16 weeks), in which adult patients with definite or probable DM (according to Bohan and Peter criteria) were randomized 1:1 to either high dose IVIg (2g/kg every 4 weeks) or placebo. Patients on placebo and patients without clinical worsening while on IVIg treatment entered the open label Extension Period (24 weeks) and received 2g/kg IVIg infusions every 4 weeks. To be included, subjects must have active disease with a manual muscle testing-8 (MMT-8) score < 142/150. Patients who showed clinical worsening (defined according to Oddis et al, 2013 - with slight adaptation) at 2 consecutive visits between week 8 and week 16 were switched to the alternate treatment arm.Primary endpoint was the proportion of responders in the IVIg vs. placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis response criteria of at least minimal improvement [Total Improvement Score (TIS) ≥ 20 points)] and without clinical worsening at 2 consecutive visits up to week 16.Results:A total of 95 adult DM patients (mean age: 53 years; 75% females; 92% Caucasian) were enrolled, with 47 and 48 randomized to IVIg and placebo, respectively. Baseline clinical characteristics (including medical history and prior DM medication) were balanced between the 2 arms.The study met the primary endpoint at week 16, with the proportion of responders being significantly higher in the IVIg group (37/47; 78.7%) as compared to the placebo group (21/48; 43.8%; p-value 0.0008; Table 1).Table 1.Total Improvement Score – Analysis of Proportion of Responders at Week 16 (Full Analysis Set, N=95)TIS Responseoctagam 10%N=47PlaceboN=48Difference octagam 10% – placeboNumber (%) of responders37 (78.72%)21 (43.75%)Difference in response rates34.97[95% CI] p-valuea[16.70, 53.24] 0.0008aCochran-Mantel-Haenszel TestCI=confidence interval; N=number of patients; TIS=total improvement scoreIn the analysis of responders per improvement category at Week 16, a 45.2% higher response rate for at least moderate improvement (TIS ≥n40 points; p < 0.0001) and a 23.6% higher response rate for at least major improvement (TIS ≥060 points; p < 0.0062) was observed in the IVIG group as compared to the placebo group.The mean (SD) TIS was significantly higher in IVIg group [48.4 (24.4)] than in placebo arm [21.6 (20.2)] at week 16 (Fig 1).Figure 1.After switching to IVIG in the Extension Period the placebo group attained a similar response rate at Week 40 as did the IVIg treated patients at Week 16, i.e approx. 70% for minimal improvement.In line with the overall primary endpoint, secondary end points including all of the sub-components of TIS except muscle enzyme (MMT-8, MD global, Extramuscular global, patient global, HAQ,) as well as CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index), also showed statistically significant improvement under IVIg treatment compared to placebo treatment.The safety and tolerability profile of IVIg was consistent with previously reported safety outcomes for IVIg administration.Conclusion:This is the first large international phase III randomized, placebo-controlled trial demonstrating the efficacy and safety of IVIg as a treatment for patients with DM.References:[1]Oddis, C. V. et al. Arthritis Rheum (2013), 65, 314–324Acknowledgements:Acknowledgments to all participating investigators, centers and patients and their familiesDisclosure of Interests:Rohit Aggarwal Consultant of: Q32, Alexion, Argenx, AstraZeneca, BMS, Boehringer Ingelheim, Corbus, Csl Behring, EMD Serono, Janssen, Kezar, Mallinckrodt, Kyverna, Octapharma, Orphazyme, Pfizer., Grant/research support from: BMS, Mallinckrodt, Pfizer, EMD Serono, Christina Charles-Schoeman Consultant of: Pfizer, Abbvie, Octapharma, Gilead, Regeneron-Sanofi, Grant/research support from: Bristol Myers Squibb, Pfizer, Abbvie, Octapharma, Joachim Schessl Speakers bureau: Octapharma, Grifols, CSL Behring, Consultant of: Octapharma, Zsuzsanna Bata-Csorgo Speakers bureau: Novartis, Sanofi-Genzyme, Ewopharma, Consultant of: Sanofi-Genzyme, Novartis, Ewopharma, Mazen Dimachkie Consultant of: ArgenX, Catalyst, Cello, CSL-Behring, EcoR1, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, RMS Medical, Sanofi Genzyme, Shire Takeda, Spark Therapeutics and UCB Biopharma., Grant/research support from: Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, UCB Biopharma, Viromed/Healixmith., Zoltán Griger Speakers bureau: Abbvie, CSL-Behring, Eli-Lilly, Roche, Boehringer Ingelheim, Consultant of: Octapharma, Sergey Moiseev: None declared, Chester V Oddis Consultant of: EMD Serono; Alexion Pharmaceuticals, Inc, Grant/research support from: Genentech (Clinical trial support); Bristol Myers Squibb (Clinical trial support), Elena Schiopu Consultant of: Octapharma, Grant/research support from: Octapharma, Janssen (Johnson & Johnson), BMS, Pfizer, Abbvie, Jirˇí Vencovský Speakers bureau: Abbvie, Biogen, MSD, Pfizer, Roche, Sanofi, UCB, Consultant of: Abbvie, Boehringer, Eli Lilly, Octapharma, Gilead, Irene Beckmann Employee of: Octapharma, Todd Levine Shareholder of: Corinthian Reference Labs, CND Life Sciences, Consultant of: Grifols, Octapharma, Alexion, Elisabeth Clodi Employee of: Octapharma PPG, Vienna Austria, and the ProDERM Investigators: None declared

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ВведениеРаспространенность фибрилляции предсердий (ФП) в европейских странах составляет около 2% и про-должает увеличиваться [1]. ФП примерно в 5 раз уве-личивает риск инсульта, который у таких пациентов ха-рактеризуется более тяжелым течением и более выра-женной инвалидизацией, чаще рецидивирует и при-водит к смерти [2]. Риск тромбоэмболических ослож-нений повышается при любых формах ФП, в том чис-ле пароксизмальной [3], поэтому при оценке необхо-димости в профилактике ишемического инсульта и системных эмболий следует учитывать не особенности течения ФП (длительность, число и тяжесть приступов, наличие постоянной аритмии и т.п.), а факторы риска тромбоэмболических осложнений, которые оцени-вают с помощью индекса CHA 2 DS 2 -VASc [4]. Если значение индекса составляет 1 или более, т.е. при на-личии хотя бы одного фактора риска, такого как пожилой возраст (≥65 лет), артериальная гипертония, инсульт или транзиторная ишемическая атака в анамнезе и др., показано лечение антикоагулянтами, которые по эф-фективности достоверно превосходили антитромбо-цитарные средства [5]. Альтернативой варфарину и дру-гим непрямым антикоагулянтам у больных с некла-панной ФП могут быть прямые пероральные ингиби-торы фактора Ха (ривароксабан, апиксабан, эдоксабан) или тромбина (дабигатран), которые оказывают более предсказуемое и стабильное антикоагулянтное действие, применяются в стандартных дозах, не требуют регу-лярного мониторирования международного норма-лизованного отношения (МНО) и реже взаимодействуют с другими лекарственными средствами [6]. По данным регистра GLORIA-AF сегодня частота применения новых пероральных антикоагулянтов у пациентов с впервые Новые пероральные антикоагулянты, ингибирующие фактор Xa (ривароксабан, апиксабан, эдоксабан) или тромбин (дабигатран), сегодня все чаще заменяют вар-фарин и другие непрямые антикоагулянты в профилактике инсульта у больных с неклапанной фибрилляцией предсердий. В рандомизированных контролируемых ис-следованиях они превосходили варфарин по некоторым показателям эффективности или безопасности, однако опыт их изучения в обычной клинической практике ограничен. Необходимость в проспективных наблюдательных исследованиях в «реальной жизни» диктуется тем, что условия проведения рандомизированных кли-нических исследований отличаются от обычной практики, что может способствовать повышению эффективности и безопасности лечения, в том числе за счет жестких критериев отбора пациентов, регулярных визитов, постоянного мониторирования безопасности и т.п. В обзорной статье приведены результаты проспективного наблюдательного исследования XANTUS, а также ретроспективных когортных исследований, в которых были показаны сходные результаты лечения новыми пероральными антикоагу-лянтами в рандомизированных клинических исследованиях и в обычной клинической практике. New oral anticoagulants that inhibit factor Xa (rivaroxaban, apixaban, edoksaban) or thrombin (dabigatran), today are increasingly replacing warfarin and other indirect anticoagulants in preventing stroke in patients with non-valvular atrial fibri...

To evaluate clinical manifestations and outcomes of Fabry disease (FD) in adult patients in the Russian population.

Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia Management of patients with atrial fibrillation (AF) includes anticoagulation for prevention of stroke and systemic embolism, improvement of AF-related symptoms by rate or rhythm control, and treatment for cardiovascular and other comorbidities. The structured characterization of AF should address four AF-related domains, that is, stroke risk, symptom severity, AF burden (type of AF, number and duration of episodes, etc.), and substrate severity. Various scores, i.e.CHA 2 DS 2 -VASc (stroke risk), HAS-BLED (bleeding risk), EHRA (severity of AF-related symptoms), and 2MACE (risk of cardiovascular events), can be used to estimate the risk of outcomes and for treatment decisions. Noteworthy, bleeding risk assessment using HAS-BLED score focuses attention on modifiable risk factors that should be managed to improve safety of anticoagulation, whereas a high bleeding risk score should not lead to withholding oral anticoagulants. New clini- cal and biomarker-based risk scores were developed. However, their potential advantages over existing scores should be confirmed in clinical studies.

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Long-acting β 2 adrenoceptor agonists (LABA) and/or longacting muscarinic antagonists (LAMA) should be used as monotherapy or in combination for the initial treatment in patients with chronic obstructive pulmonary disease (COPD). Triple inhaled therapy with LABA, LAMA, and inhaled corticosteroid (ICS) has been recommended for COPD patients who still have clinically significant symptoms following the use of a dual inhaler with LABA plus LAMA, particularly for those who present with frequent exacerbations, blood eosinophilia and/or concomitant bronchial asthma. Experimental studies on human isolated airways suggested that LABA, LAMA, and ICS synergistically relax the medium and small bronchi probably as a result of enhanced elevation of the cyclic adenosine monophosphate (cAMP) that mediates relaxation of airway smooth muscle cells. Synergy of LABA and LAMA was also shown in a few clinical studies, whereas in the randomized controlled trials triple therapy with two long-acting bronchodilatators and ICS was more effective than various dual combinations (LABA/LAMA or ICS/LABA) in patients with severe COPD. These findings justify triple therapy in patients with severe COPD who have frequent exacerbations and do not respond to dual therapy. Recently, a single inhalers containing ICS, LABA, and LAMA have been developed as a more practical alternative, which may improve therapy compliance.