Abstract The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission.

O 4-nitro-2-fenoximetanosulfonanilide (nimesulide), antiinflamatório não esteróide, vem sendo utilizado no tratamento de quadros inflamatórios devido à sua atividade farmacológica nestes mecanismos de resposta as injúrias flogísticas. O objetivo do presente trabalho é estudar a ação deste fármaco sobre duas importantes funções neutrofílicas: quimiotaxia e produção de ânion superóxido após pré incubação com doses crescentes da droga (0,1; 0,3 e 0,5mM). Os resultados obtidos demonstram que a pré-incubação de PMNs coletados do sangue periférico de indivíduos normais com o 4-nitro-2-fenoximetanosulfonanilide reduz significativamente a produção de superóxido por estimulação de PMN com acetato de forbol miristato (PMA 50ng/ml). formil metionil leucil fenilalanina (FMLP 10-'M e Zimozan opsonizado (1mg/ml). Adicionalmente o fármaco se mostrou igualmente efetivo em reduzir a habilidade quimiotáxica de PMNs, frente ao fator C5a (2% de soro ativado por zimozan). FMLP (10-9M) e leucotrieno B4 (3x10-'M). Os resultados obtidos sugerem que além da sua atividade a nível do metabolismo do ácido araquidônico, o 4-nitro-2-fenoximetanosulfonanilide possa interferir diretamente sobre a função neutrofílica, o que provavelmente contribui para sua ação antiinflamatória.

4-nitro-2-phenoximethanesulphonanilide (nimesulide) is a nonsteroidal anti-inflammatory agent that has been employed in the treatment of inflammatory diseases because of its specific actions on the inflammatory response mechanisms caused by injury. The objectives of this paper were to determine the action of this agent on two notable neutrophil functions, chemotaxis and production of the superoxide anion. These two functions were studied after the neutrophils were pre-incubated with three different concentrations of 4-nitro-2-phenoximethanesulphonanilide (0.1; 0.3 and 0.5 mN). The results obtained herein demonstrated that 4-nitro-2-phenoximethanesulphonanilide-exposed peripheral blood neutrophils from healthy subjects produced significantly less superoxide when challenged by phorbol-mirystate acetate (PMA at 50 ng/ml) or formy-methionil-leucyl-phenilalanine (FMLP 10 -7 M) and opsonizided zymozan (1 mg/ml). Additionally, the agent was equally effective in reducing the PMN chemotoaxis when challenged by C5a factor (2% zimozan activated solution), FMLP 10 -9 M and leukotrien (3. 10 -7 M). The results obtained suggest that in addition to its interference in the metabolism of the aracdonic acid, the 4-nitro-2 phenoximethanesulphonanilide may interfere in a more direct fashion with the neutrophil function. This specific action may contribute to its anti-inflammatory activity.