Abstract Background Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. Methods A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. Results Six recommendations were elaborated regarding the pharmacological treatment of Raynaud’s phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. Conclusion These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice. (SSc manifestations decade (RCTs PatientPopulation Patient Population Patient/Population Intervention Comparison PICO (PICO Assessment GRADE (GRADE methodology recommendation 75 needed Raynauds Raynaud s phenomenon healing (healing ulcers ILD (ILD drugs rituximab placebocontrolled placebo controlled found decisionmaking decision making practice 7

Abstract Background: Recommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM). Main body: The review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies. Conclusions: Robust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strengthbuilding and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

RESUMO Com base na vasta experiência de uso, segurança e eficácia comprovada na redução de fraturas vertebrais, não vertebrais e femorais, os bisfosfonatos são considerados agentes de primeira linha no tratamento da osteoporose pós-menopáusica. No entanto, os relatos pós-venda baseados no tratamento de milhões de pacientes/ano durante períodos prolongados de tempo revelaram a ocorrência de efeitos adversos inicialmente inesperados, como osteonecrose da mandíbula e fratura atípica do fêmur. Isso levou as agências reguladoras globais a restringirem a duração do tratamento com bisfosfonatos. No entanto, apesar da associação entre esses efeitos e os bisfosfonatos, esse risco deve ser analisado no contexto do tratamento da osteoporose, paralelamente ao benefício na prevenção de fraturas osteoporóticas e suas consequências clínicas. Portanto, considera-se plausível discutir a restrição ao uso dos bisfosfonatos, possíveis indicações para o tratamento prolongado e terapias opcionais após a suspensão dessa classe de fármaco para pacientes com alto risco persistente de fratura após o tratamento inicial, especialmente se considerarmos os problemas financeiros de saúde pública no Brasil e a escassez de fármacos fornecidos pelo governo. Assim, para padronizar o tratamento da osteoporose no sistema público de saúde pretende-se desenvolver uma proposta de tratamento farmacológico cientificamente fundamentada para a osteoporose pós-menopáusica, estabelecer critérios de indicação e permitir o uso racional de cada agente farmacológico. Discutem-se a duração do tratamento inicial com bisfosfonatos, as opções terapêuticas para pacientes refratários e potenciais indicações de outras classes de medicamentos como tratamento de primeira linha na esfera da saúde pública, em que a avaliação do risco e custo-efetividade é uma prioridade.

ABSTRACT Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

Resumo A osteoporose é a principal causa de fraturas na população acima de 50 anos. É uma doença silenciosa que afeta especialmente as mulheres na pós-menopausa e idosos e tem elevada taxa de morbimortalidade. O principal objetivo do tratamento da osteoporose é a prevenção das fraturas. A identificação dessa população de risco através do diagnóstico e tratamento precoces é de fundamental importância. A última diretriz brasileira para tratamento da osteoporose em mulheres na pós-menopausa foi elaborada em 2002. Desde então foram desenvolvidas novas estratégias de diagnóstico da osteoporose, bem como fármacos com novos mecanismos de ação foram adicionados ao arsenal terapêutico. A Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia em conjunto com a Associação Médica Brasileira e sociedades afins desenvolveu esta atualização da diretriz do tratamento da osteoporose em mulheres na pós-menopausa de acordo com as melhores evidências científicas disponíveis. Esta atualização é destinada aos profissionais das várias especialidades médicas e da área da saúde envolvidos no tratamento da osteoporose, médicos em geral e organizações relacionadas à saúde.

Abstract Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations.

A maioria das informações relativas ao curso da doença de pacientes com lúpus eritematoso sistêmico (LES) é restrita aos primeiros cinco anos após o diagnóstico. Entretanto, dados sobre a precocidade de instalação dos danos são pouco descritos. OBJETIVO: identificar os danos precoces de pacientes com LES de diagnóstico recente e verificar a influência da própria doença ou de sua terapêutica como principal causa para a instalação destes danos. MÉTODOS: foram estudados retrospectivamente 82 pacientes com LES, cujo diagnóstico foi realizado de 1998 até 1999 em nosso serviço. Em todos os pacientes o escore do índice de dano do Systemic Lupus Internacional Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR-DI) foi avaliado no momento do diagnóstico e anualmente três vezes consecutivas. As manifestações clínicas e o esquema terapêutico foram avaliados nas consultas médicas. O escore do SLICC/ACR para cada órgão/sistema e a prevalência dos danos foi identificado, assim como a sua possível causa (doença ou terapia). RESULTADOS: A idade (média) inicial foi de 31,6 anos com predomínio do sexo feminino (94%). A maioria dos pacientes (94%) apresentou manifestações cutâneas e articulares, seguidas pelas renais (40%), pulmonares (28%) e neurológicas (18%). Ao final do estudo, 52 pacientes (63,4%) não apresentaram seqüelas (sem pontuação no SLICC). Dos 30 pacientes restantes, 16 tiveram escore = 1 e 14 pacientes apresentaram escore = 2. No total observamos 36 danos, sendo 23 atribuídos à doença e 13 à terapia (64% vs 36%, p < 0,05). Os sistemas mais freqüentemente acometidos foram o articular e o neurológico (27,7%), seguidos pelo renal (13,8%). Todos os pacientes com comprometimento neurológico tiveram danos precoces decorrentes da própria doença (apesar da terapêutica agressiva) enquanto a terapêutica com corticóide foi responsável pelos danos em 7/10 pacientes com dano articular (osteonecrose). O dano renal foi observado em 13,8% dos pacientes (nefrite grave não responsiva ao tratamento). Outros efeitos adversos da terapia foram angina, catarata, diabetes e menopausa precoce. CONCLUSÕES: este estudo sugere que o dano precoce é ainda um importante problema no LES. São necessárias estratégias eficazes no sentido de minimizar as seqüelas, com destaque para as neurológicas. Redução da morbidade associada à terapia com corticóide também deve ser considerada utilizando-se agentes poupadores de esteróides.

The majority of the information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first five years after disease onset. However, data about early damage were rarely reported. OBJECTIVE: to describe the early damage outcome of SLE patients in early disease and to discriminate the influence of disease itself or its therapy as the main cause of their damage. METHODS: we retrospectively studied 82 patients with SLE, diagnosed during the period from 1998 to 1999 in our institution. In all patients the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) was scored at the diagnosis and annually for the next three years. Clinical manifestations were evaluated at each visit as well as the therapy. The SLICC/ACR-DI scores for each organ system and the prevalence of damage within organ systems were assessed, as well as its possible main cause (disease or therapy). RESULTS: the mean age at entry was 31.6 years with female predominance of 94%. The majority of the patients (94%) presented cutaneous and articular involvement, 40% renal, 28% pulmonary, and 18% neurological manifestations. At the end of the study, 52 (63.4%) patients had no damage to score with SLICC. From the remaining 30 patients, 16 had a score of 1 and 14 had a score = 2. In total, 36 damages occurred, 23 of them attributed to the disease and 13 to the therapy (64% vs. 36%; p < 0.05). The most frequently injured systems were the articular and the neurological (27.7%) ones, followed by the renal (13.8%) system. All patients with neurological involvement have early damage due to the disease itself in spite of the aggressive therapeutic whereas from 10 patients with articular damage, 70% (7) were associated with steroid therapy (osteonecrosis). In contrast, premature renal injury was observed in 13.8%, all of them with unresponsive severe nephritis. Other adverse effect of therapy included 1 angina, 2 cataracts, 1 diabetes and 2 premature menopauses. CONCLUSIONS: this study suggests that early damage is still a major problem in SLE that reinforces the need for new strategies in order to minimize injury, particularly for neurological manifestations. Moreover, it also seems important to reduce morbidity induced by corticosteroid therapy with the use of steroid-sparing agents.