Introdução: A Hipertensão Arterial Pulmonar está associada a uma ampla gama de doenças, sendo comum nas doenças do tecido conjuntivo. Porém, um dos maiores desafios diagnósticos em relação à Hipertensão Arterial Pulmonar inclui doenças do tecido conjuntivo clinicamente não identificadas ou tardiamente evidenciadas, principalmente Esclerose Sistêmica. Objetivos: Relatar casos de Hipertensão Arterial Pulmonar secundária à Esclerose Sistêmica que inicialmente foi classificada como Idiopática. Materiais e métodos: Estudo observacional analítico transversal no qual sete pacientes com diagnóstico de Hipertensão Arterial Pulmonar Idiopática foram avaliados quanto ao quadro clínico, exame físico, pesquisa de autoanticorpos e capilaroscopia periungueal na busca de critérios que os classificassem como Esclerose Sistêmica. Resultados: Todos os pacientes preencheram os Critérios Classificatórios para Esclerose Sistêmica ACR/EULAR 2013, sendo que Fenômeno de Raynaud, telangiectasias e positividade de autoanticorpos estiveram presentes em 100% dos casos. A maioria dos pacientes apresentava Esclerose Sistêmica forma cutânea limitada. Conclusões: A determinação do diagnóstico de Hipertensão Arterial Pulmonar secundária à Esclerose Sistêmica é fundamental, pois tais pacientes têm menor sobrevida quando comparados aos casos Idiopáticos. A presença de Fenômeno de Raynaud tem grande relevância no diagnóstico dos pacientes com Hipertensão Arterial Pulmonar associada à Esclerose Sistêmica.

Objectives To test the association of use of antimalarials with the overall safety of treatment in rheumatoid arthritis (RA) patients receiving one or multiple courses of biologic (b-) DMARDs or a Janus kinase inhibitor (JAKi). Methods BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from Jan 2009 to Oct 2019, followed-up over one or multiple (up to six) courses of treatment (latest date, Nov 19, 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. Results 1316 patients (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials) were enrolled. The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49, 95% CI: 0.36–0.68, P< 0.001), total adverse events (0.68, 0.56–0.81, P< 0.001), serious infections (0.53, 0.34–0.84, P= 0.007) and total hepatic adverse events (0.21, 0.05–0.85, P= 0.028). Antimalarials were also related to better survival of treatment course (P= 0.003). There was no significant increase in the risk of cardiovascular AEs. Conclusion Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Objective To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease modifying anti-rheumatic drugs (DMARDs) or JAK inhibitors (JAKi). Methods RA patients starting the first treatment course with a csDMARD (without previous use of biologic or JAKi) or first bDMARD/JAKi were followed-up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matched analysis (PSMA) were used for statistical comparisons. Results In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX plus LEF. The overall incidence of SAEs was 5.6/100 PY. The hazard of SAEs for MTX plus LEF was not higher than for MTX or LEF (adjusted hazard ratio: 1.00, 95% CI, 0.76 to 1.31, P=0.984). The MTX-LEF combo presented a lower hazard of SAEs (0.56, 0.36 to 0.88, P=0.011) and infectious SAEs (0.48, 0.25 to 0.94, P=0.031) than bDMARDs/JAKi with MTX or LEF. MTX plus LEF presented lower hazard of SAEs than MTX plus SSZ (0.33, 0.16 to 0.65, P=0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. Conclusion In our study, MTX plus LEF presented a relatively good overall safety profile in comparison to MTX plus SSZ and schemes involving advanced therapies in RA.

Doenças sistêmicas podem apresentar alterações enteseais, estruturais ou inflamatórias, e, portanto, podemos necessitar avaliar estas hipóteses diagnósticas na investigação de uma entesopatia. Entre estas patologias, destacam-se as de origem metabólica, como o hipoparatireoidismo idiopático e o hiperparatireoidismo, associado à hipofosfatasia ou à insuficiência renal crônica, e a ocronose, nos casos com acometimento principalmente axial, e a diabetes mellitus, a acromegalia e a hipercolesterolemia familiar, em que predominam os quadros periféricos. Além deste grupo, é interessante incluir a doença celíaca nos casos de entesopatia e sintomas gastrointestinais, e incluir algumas infecções, como tuberculose, em casos mais localizados e agressivos. Também há relatos de associação de algumas drogas, em especial os retinoides, a alterações enteseais, principalmente a entesopatias axiais. Desta forma, a avaliação global do paciente, incluindo sintomas sistêmicos, alterações metabólicas, comorbidades existentes e medicações em uso, é muito importante durante a investigação de uma entesopatia. Unitermos: Entesopatia. Entesite. Doenças sistêmicas. Diagnóstico diferencial.

Background:After failure of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in the therapy of rheumatoid arthritis (RA), treatment may be escalated to biologic (bDMARDs) or JAK inhibitors (JAKi) (1). Analysis of drug survival can provide useful information on the effectiveness of these therapeutic schemes.Objectives:to evaluate the association of the choice of therapeutic agent with the survival of treatment course in RA patients receiving their first bDMARD or JAKi.Methods:BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients starting their first bDMARD/JAKi (2). This analysis includes RA patients recruited from Jan 2009 to Oct 2019, followed-up over the first course of treatment with a bDMARD/JAKi until censoring (latest date, Nov 19, 2019) or occurrence of the outcome of interest. A treatment course is defined as a period during which the medication scheme does not change, except for dose adjustments. The primary outcome was the interruption of treatment course for any reason (except for pregnancy or disease remission); interruption of treatment due to adverse events (AEs) or death and due to inefficacy served as secondary outcomes. Multivariate Cox proportional hazards models were used for analyses.Results:In total, 1177 patients (3800 patient-years [PY]) were enrolled. The overall incidence of treatment interruption was 17.5/100 PY. Adalimumab was the most frequently prescribed agent, followed by infliximab (n= 267). The hazards ratios (HR) of the primary and secondary outcomes are presented in Table 1. Figure 1 compares the survival of treatment curves of different bDMARDs/JAKi.Table 1.Hazard ratios (HR) of interruption of therapy course of each therapeutic agent (the reference category for bDMARDs/ JAKi is infliximab). Results are HR, 95% CIs, and P values*.Agent (number of patients)Interruption for any reason (665 events)Interruption due to adverse events or death (196 events)Interruption due to inefficacy (319 events)Adalimumab (354)0.83 (0.68 to 1.01), P= 0.0620.68 (0.48 to 0.96), P=0.0291.08 (0.80 to 1.44), P=0.621Etanercept (257)0.81 (0.66 to 1.01), P=0.0630.56 (0.37 to 0.83), P=0.0040.93 (0.68 to 1.29), P=0.674Certolizumab (80)0.74 (0.47 to 1.16), P=0.1850.33 (0.13 to 0.86), P=0.0241.32 (0.74 to 2.35), P=0.350Golimumab (53)0.86 (0.53 to 1.38), P=0.5300.46 (0.18 to 1.19), P=0.1111.07 (0.53 to 2.15), P=0.849JAKi (tofacitinib) (59)0.54 (0.30 to 0.99), P=0.0470.19 (0.04 to 0.82), P=0.0260.89 (0.41 to 1.96), P=0.779Rituximab (48)0.87 (0.55 to 1.37), P=0.5400.48 (0.20 to 1.18), P=0.1090.58 (0.26 to 1.34), P=0.205Abatacept (30)0.52 (0.25 to 1.07), P=0.0770.46 (0.14 to 1.56), P=0.2150.46 (0.14 to 1.52), P=0.203Tocilizumab (29)0.29 (0.14 to 0.63), P=0.0020.40 (0.12 to 1.30), P=0.1260.28 (0.09 to 0.90), P=0.033Methotrexate (792)0.95 (0.79 to 1.14), P=0.5610.86 (0.62 to 1.19), P=0.3620.98 (0.75 to 1.28), P=0.860Leflunomide (497)1.17 (0.99 to 1.39), P=0.0611.44 (1.06 to 1.96), P=0.0201.02 (0.80 to 1.30), P=0.856Sulfasalazine (48)1.18 (0.80 to 1.75), P=0.4011.94 (1.07 to 3.54), P=0.0300.85 (0.45 to 1.59), P=0.605Antimalarials (230)0.80 (0.65 to 0.98), P=0.0270.67 (0.45 to 0.99), P=0.0430.67 (0.50 to 0.92), P=0.011* All tests adjusted for other variables presented in the table and for age, baseline DAS28, disease duration, gender, smoking, seropositivity (RF/anti-CCP), previous malignancy, diabetes, hypertension, hypercholesterolemia, renal failure, ischemic cardiomyopathy, COPD, heart failure, use of corticosteroids, starting year, hypercholesterolemia, osteoporosis, hepatitis B and C.Conclusion:In our study, infliximab was related to an overall higher hazard of treatment course interruption than tolicizumab and tofacitinib, and higher hazard of interruption due to AEs than most other anti-TNF agents and tofacitinib. Maintaining antimalarials in patients receiving advanced therapies for RA may reduce interruption of treatment due to inefficacy and AEs.Disclosure of Interests:None declared