ТАРГЕТНАЯ ТЕРАПИЯ И ИНФЕКЦИИ ПРИ РЕВМАТИЧЕСКИХ ЗАБОЛЕВАНИЯХ

In the past decade, rheumatology has shown clear progress in the practical introduction of biological agents (BAs) and targeted sintetic anti-inflammatory agents. At the same time, the use of these agents is associated with an increasing risk for infections of different origin and sites, including opportunistic infections (invasive my-coses, Pneumocystis pneumonia, etc.), as well as an increased risk for reactivation of latent infections, primarily tuberculosis (TB). In addition, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc.), including those with a fatal out-come. The review analyzes the literature data (mainly in the last 5 years) regarding the frequency and localization of infections in rheumatologic patients treated with BAs. It characterizes the significance of various infections (TB, pneumonia, chronic viral hepatitis, herpesvirus infection, etc.) in the tactics of following up these patients. The authors emphasize the need for the more widespread use of various vaccines (especially those against influenza and pneumococcal infection) in patients with autoimmune inflammatory rheumatic diseases.В последние десятилетия в ревматологии отмечается явный прогресс, связанный с внедрением в практику генно-инженерных биологических препаратов (ГИБП) и таргетных синтетических противовоспалительных препаратов. В то же время применение этих препаратов ассоциируется с нарастающим риском развития инфекций разнообразной природы и локализации, включая оппортунистические (инвазивные микозы, пневмоцистная пневмония и др.), а также повышенный риск реактивации латентной инфекции, в первую очередь туберкулеза (ТБ). Помимо этого регистрируются случаи тяжелых инфекций (пневмония, сепсис, бактериальный артрит, поражение кожи и мягких тканей и др.), в том числе с летальным исходом. В статье проанализированы данные литературы (преимущественно за последние 5 лет), касающиеся частоты и локализации инфекций у больных ревматологического профиля при лечении ГИБП. Охарактеризована значимость различных инфекций (ТБ, пневмонии, хронические вирусные гепатиты, герпес-вирусные инфекции и др.) в тактике курации указанных больных. Подчеркнута необходимость более широкого применения иммунизации различными вакцинами (в первую очередь против гриппа и пневмококковой инфекции) пациентов с аутоиммунными воспалительными ревматическими заболеваниями

ASSESSMENT OF THE IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATIC DISEASES

Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD).Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7%) women and 31 (23.3%) men) aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA), 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group), who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia). At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT), 14 – leflunomide (LEF), and 13 – MT + tumor necrosis factor-α (TNF-α) inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination). The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom).Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68%) patients displayed no adverse events; 37 (28%) had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4%) had low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD

Оценка клинической эффективности, иммуногенности и безопасности 23-валентной пневмококковой вакцины у больных ревматоидным артритом

The objective of this trial was to assess clinical efficacy, immunogenicity, and safety of 23valent pneumococcal vaccine (PPV23) in patients with rheumatoid arthritis (RA).Methods. The trial enrolled 95 patients (75 women and 20 men aged 23 to 70 years) including 68 patients with RA and 27 subjects without systemic inflammatory rheumatic diseases (a control group) who had a recent history of ≥ 2 episodes of lower respiratory tract infection. At enrollment, all the patients received antiinflammatory therapy with methotrexate (MT) (n = 48), leflunomide (LEF) (n = 10), or MT + tumor necrosis factorα (TNFα) inhibitors (n = 10). A single 0.5ml dose of PPV23 (Pneumo23, Sanofi Pasteur) was administered subcutaneously under the regular therapy with MT or LEF or 3–4 weeks before TNFα inhibitor administration. During followup (1 and 3 months and 1 year after the vaccination), the patients underwent physical examination and routine clinical and laboratory investigations. Antipneumococcal capsular polysaccharide antibodies were measured in the serum using ELISA assay with commercial VaccZymeTM AntiPCP IgG Enzyme Immunoassay Kit (The Binding Site Group Ltd, Birmingham, UK).Results. Noone case of pneumonia was registered in vaccinated patients during 12month followup. A twofold increase in antipneumococcal antibody level was found 1 year after the vaccination in RA patients and the control group. The vaccine was well tolerated by 63 patients (66%); 25 patients (26%) experienced pain, swelling and hyperemia at the area of vaccine injection and 7 patients (8%) had lowgrade fever. Neither RA exacerbation nor new autoimmune disorders were diagnosed during the followup.Conclusion. The findings suggest that PPV23 showed good clinical efficacy, adequate immunogenicity and good tolerability in RA patients.Цель. Изучение клинической эффективности, иммуногенности и безопасности 23валентной полисахаридной пневмококковой вакцины (ППВ23) у больных ревматоидным артритом (РА).Материалы и методы. В исследование были включены пациенты (n = 95: 75 женщин и 20 мужчин в возрасте 23–70 лет), больные РА (n = 68) и лица (n = 27) без системных воспалительных ревматических заболеваний (контрольная группа), имеющие в ближайшем анамнезе ≥ 2 случаев инфекций нижних дыхательных путей (бронхиты, пневмонии). На момент включения все больные получали противовоспалительные препараты: 48 – метотрексат (МТ), 10 – лефлуномид (ЛЕФ), 10 – МТ + ингибиторы фактора некроза опухолиα (TNFα). Вакцинация ППВ23 «Пневмо23» (Sanofi Pasteur, Франция) проводилась однократно в дозе 0,5 мл подкожно на фоне продолжения терапии основного заболевания МТ или ЛЕФ, либо за 3–4 нед. до назначения ингибиторов TNFα. Во время контрольных визитов (через 1, 3 и 12 мес. после введения вакцины) проводились клинический осмотр больного, общепринятые клинические и лабораторные исследования. Уровни антител (АТ) к капсульному полисахариду пневмококкав сыворотке крови определялись методом иммуноферментного анализа с помощью коммерческих наборов VaccZymeTM Anti*PCP IgG Enzyme Immunoassay Kit (The Binding Site Group Ltd, Birmingham, Великобритания).Результаты. В течение периода наблюдения (12 мес.) клинических и рентгенологических симптомов пневмонии не зарегистрировано ни в одном случае. У больных РА и в группе контроля отмечено более чем 2кратное значимое повышение содержания пневмококковых АТ через 1 год после вакцинации. Переносимость вакцинации была хорошей у 63 (66 %) человек; у 25 (26 %) пациентов отмечена боль, припухлость и гиперемия кожи диаметром до 2 см в месте инъекции вакцины, у 7 (8 %) – субфебрилитет. Эпизодов обострения РА или возникновения какихлибо новых аутоиммунных расстройств в течение периода наблюдения не отмечено.Заключение. Полученные данные свидетельствуют о хорошей клинической эффективности, достаточной иммуногенности и хорошей переносимости ППВ23 у больных РА

VACCINATION IN RHEUMATOLOGY: EVOLUTION OF VIEWS ON THE PROBLEM

In the present-day rheumatology, comorbid infections represent a relevant issue; their formation is caused both by the rheumatic disease (RD) and the need to use drugs with immunosuppressive action. Numerous problems caused by infections in rheumatology and other branches of clinical medicine can not be solved only by using a large number of anti-infective drugs that are available today. Therefore, in the near future, a critical role will belong to the development, improvement and prompt (if possible) introduction of various vaccines into clinical practice. The current review touches upon questions relating to the use of vaccines against influenza and pneumococcal infections in patients with RD, and formulates the prospects for further implementation of vaccination in rheumatology

Vaccination in rheumatology: the present and prospects

In modern rheumatology, comorbid infections (CIs) have a great impact on morbidity and mortality, in systemic connective tissue diseases in particular. In this connection, much attention is given to the intense introduction of different vaccines into rheumatological care. Much evidence suggests that immunization has no negative influence on the course of the underlying rheumatic disease (RD). The efficiency and safety of vaccination to prevent respiratory tract infections as the most important CIs are demonstrated. The fundamentals of the EULAR vaccination guidelines and the key areas of future investigations into this problem are presented

VACCINATION IN RHEUMATOLOGY: CURRENT ASPECTS

Infectious diseases still remain a serious social and medical problem. The importance of comorbid infections in rheumatology has increased substantially in recent years, particularly due to the clinical introduction of biologicals. The investigation and active use of different vaccines are one of the ways to solve the above problem. This review considers the issues concerning the use of vaccines against influenza, infections caused by pneumococci, herpesviruses, human papillomavirus, and hepatitis B virus in rheumatology patients. It discusses the safety and immunogenicity of vaccination associated with the prevention of airway infections as the most common cause of a poor outcome in rheumatic diseases. The main areas of future investigations in the problem under consideration are defined

TARGETED THERAPY AND INFECTIONS IN RHEUMATIC DISEASES

In the past decade, rheumatology has shown clear progress in the practical introduction of biological agents (BAs) and targeted sintetic anti-inflammatory agents. At the same time, the use of these agents is associated with an increasing risk for infections of different origin and sites, including opportunistic infections (invasive my-coses, Pneumocystis pneumonia, etc.), as well as an increased risk for reactivation of latent infections, primarily tuberculosis (TB). In addition, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc.), including those with a fatal out-come. The review analyzes the literature data (mainly in the last 5 years) regarding the frequency and localization of infections in rheumatologic patients treated with BAs. It characterizes the significance of various infections (TB, pneumonia, chronic viral hepatitis, herpesvirus infection, etc.) in the tactics of following up these patients. The authors emphasize the need for the more widespread use of various vaccines (especially those against influenza and pneumococcal infection) in patients with autoimmune inflammatory rheumatic diseases

The Use of 23-Valent Pneumococcal Polysaccharide Vaccine in Patients with Rheumatoid Arthritis

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 102 patients (78 women and 24 men, aged 23 – 70 years), including 72 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 52), leflunomide (LEF) (n = 10), or MT + tumor necrosis factor-α (TNF-α ) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine was administered subcutaneously during continuous MT or LEF therapy for the underlying disease or 3 – 4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies.Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 67 patients. 27 patients were observed to have pain, cutaneous swelling and hyperemia and 8 patients had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up.Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA