Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate.

OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept. METHODS: In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [∼10 mg/kg] on day 1) or IV abatacept (∼10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed. RESULTS: Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept-treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept-treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval -4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept-treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept-treated group and 65.2% and 4.9%, respectively, in the IV abatacept-treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)-treated patients (2.6%) and 18 IV abatacept (SC placebo)-treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept-treated patients and 2.3% of IV abatacept-treated patients. CONCLUSION: SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.

Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate.

OBJECTIVES: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. METHODS: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. RESULTS: Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. TRIAL REGISTRATION NUMBER: NCT00095147.

Long-Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate-to- Severe Systemic Lupus Erythematosus: Results From an Open-Label Extension Study.

OBJECTIVE: The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL). METHODS: Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed. RESULTS: A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab. CONCLUSION: Open-label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.

Subsidios para a implementacao de um programa de prevencao reumatologica a nivel de saude publica. / On the implementation of public health prevention programs for chronic rheumatoid diseases

A grande prevalencia dos reumatismos cronicos como doenca incapacitantes e de grande impacto socio-economico torna a implantacao de programas de prevencao primaria e secundaria na area da Reumatologia de importancia fundamental. A Organizacao Pan-Americana de Saude,desde junho de 1983 vem enfatizando tais aspectos e recomendando aos paises-membros uma postura definida no combate aos reumatismos, dentro das estruturas de saude existentes e visando os fatores de risco conhecidos. O presente trabalho revisa os aspectos teoricos e praticos necessarios para implementacao de programas de saude publica no ambito da Reumatologia e faz recomendacoes acerca de programas de acao regionalizados em nosso pais

Fibrose pulmonar na esclerose sistêmica progressiva: frequência e associações clínicas / Pulmonary fibrosis in progressive systemic sclerosis: frequency and clinical associations

A esclerose sistêmica progressiva (ESP) é uma doença crônica caracterizada por vasculopatia disseminada e fibrose tecidual. O envolvimento intersticial pulmonar constitui uma de suas principais causas de morbimortalidade. Foram estudados 22 pacientes (20 mulheres, 2 homens) com ESP (14 com forma limitada, 8 com forma difusa) quanto à presença de fibrose pulmonar através de tomografia computadorizada (TC). Em 13 pacientes (59 por cento), fibrose pulmonar foi documentada tomograficamente. O RX de tórax foi normal em 6 destes 13 pacientes; nos outros 7 casos, as alterações tomográficas foram mais precoces e definidas do que as encontradas no RX de tórax. Em dois terços dos pacientes com fibrose pulmonar o espirograma simples foi alterado. A presença de estertores crepitantes bibasais constitui-se na anormalidade respiratória mais frequente nos pacientes com fibrose pulmonar. Variáveis como sexo, raça, presença de fatores antinucleares (FAN), padrões de FAN, tosse e dispnéia não foram estatisticamente distintos nos pacientes com ou sem fibrose pulmonar. A frequência de fibrose pulmonar nessa casuística de ESP foi intermediária, considerando-se os contrastantes dados de literatura. A TC foi claramente mais sensível do que o RX de tórax no diagnóstico de alterações fibróticas

Anticorpos "anti-human T lymphotropic" vírus tipos I e II (HTLV-I/II) em pacientes com artrite reumatóide / Antibodies anti-human T lymphotropic virus types I and II (HTLV-I/II) in pacients with rheumatoid arthritis

HTLV-I/II são oncorretrovírus associados à leucemia de células T do adulto e à mielopatia crônica progressiva. Poliartrite crônica simétrica e complexo sicca são eventualmente encontrados em casos de infecções por HTLV-I/II. Um recente estudo japonês evidenciou prevalência de 20 por cento de anticorpos anti-HTLV-I em pacientes com artrite reumatóide (AR), um achado significante comparativamente a controles de banco de sangue. Tanto quanto os autores sabem, não há estudos brasileiros a esse respeito. Objetivo: Avaliar a prevalência de anticorpos anti-HTLV-I/II em pacientes com AR, usando um ensaio enzimático (ELISA) e, quando necessário, Western blot para confirmação de positividade. Métodos: Foram estudados 69 pacientes com AR (55 mulheres e 14 homens, todos caucasóides), diagnosticados de acordo com os critérios do Colégio Americano de Reumatologia. A média de idade dos pacientes foi de 51 anos, e a duração média da doença, de 8 anos. Os soros desses pacientes foram inicialmente testados para anticorpos anti-HTLV-I/II em ELISA de segunda geração (Ortho). A positividade foi confirmada através de Western blot (Gene Labs, kit 2.4). Os grupos-controles consistiram de 1.416 doadores de banco de sangue testados por ELISA e 33 pacientes consecutivos com lúpus eritematoso sistêmico (LES), também testados em ELISA. O teste de Fisher foi utilizado para análise estatística, sendo valores de p<0,05 considerados relevantes. Resultados: Anticorpos anti-HTLV-I/II foram detectados em 5 dos 69 pacientes com AR através de ELISA (7 por cento). Destes, 4 (5,7 por cento) tiveram resultados confirmatórios para anti-HTLV-I em Western blot. Os 4 pacientes eram soropositivos para fator reumatóide, mas nenhum apresentava doença ativa. Nos doadores de sangue, 18 soros (1,27 por cento) foram positivos para anti-HTLV-I/II em ELISA (p=0,004, significativo em relação ao grupo com AR testado em ELISA). Nos pacientes com LES, nenhum caso de positividade foi encontrado em ELISA (p=0,07, insignificante em relação aos pacientes com AR). Conclusão: No estudo, a prevalência de anticorpos contra HTLV-I/II em pacientes com AR foi estatisticamente relevante quando comparada com a de doadores de sangue, mas não-significativa quando comparada com a de pacientes com LES. O papel da infecção por HTLV-I/II na AR deve ser clareado em estudos adicionais