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.

Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes.

OBJECTIVE: To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). METHODS: The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. RESULTS: Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. CONCLUSIONS: The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. TRIAL REGISTRATION: NCT00122382.

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors.

OBJECTIVES: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. METHODS: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. RESULTS: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. CONCLUSIONS: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.

Cutaneous polyarteritis nodosa in a child with positive antiphospholipid and P-ANCA.

A case of juvenile cutaneous polyarteritis nodosa (cutaneous PAN) is presented. Since early infancy the child underwent attacks of fever and cutaneous rash that occasionally progressed to gangrene and amputations of distal portions of toes and fingers. Although occasional episodes of high blood pressure and persistence of moderate eosinophilia were present, the clinical pattern was mostly restricted to the musculoskeletal system and skin. The authors discuss the definition of the disease and its present therapeutic possibilities, calling attention to a feature not referred in previous reports: the unique co-existence of cutaneous PAN plus antiphospholipid antibodies (aPL) and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA).

Quantificaçäo da interferência do soro na fagocitose de imunocomplexos nas espondiloartropatias soronegativas, lúpus eritematoso sistêmico e doença reumatóide / Quantification of serum interference in the immune complexes phagocytosis in seronegative spondylarthropaties, systemic lupus erythematosus and rheumatoid disease

Cinqüenta e cinco soros de pacientes portadores de espondiloartropatias soronegativas, lúpus eritematoso sistêmico e artrite reumatóide foram selecionados para o estudo. Todos os soros mostravam fator reumatóide negativo pela prova de látex. A determinaçäo da interferência na fagocitose de gamaglobulina agregada por macrófagos de cobaia foi obtida por uma fórmula. A caracterizaçäo dos soros foi discriminada pela reaçäo daqueles que mostraram resultados mais expressivos na interferência sobre a fagocitose, facilitando ou inibindo-a. Os resultados, em valores absolutos e percentuais, mostraram a predominância do fenômeno da interferência na fagocitose, com valores significantes estatisticamente (p<0,05), quando comparado com soro normal. A análise comparativa entre as doenças estudadas na quantificaçäo da interferência do soro na fagocitose de imunocomplexo näo mostrou diferença significativa. A inibiçäo da fagocitose ocorreu com mais predominância no soro de pacientes com síndrome de Reiter e artrite psoriática; no soro de pacientes com síndrome de Reiter houve uma diferença estatisticamente significante na inibiçäo da fagocitose (p=0,0247). A caracterizaçäo da fraçäo sérica responsável pela interferência na fagocitose näo foi demonstrada. No estado atual dos conhecimentos, näo há uniformidade nas curvas de diluiçäo estudadas. É enfatizada a possibilidade de existência de mais de um elemento interferindo na fagocitose de imunocomplexos.

[Quantification of serum interference in immune complex phagocytosis in seronegative spondylarthropaties, systemic lupus erythematosus, and rheumatoid disease]. / Quantificação da interferência do soro na fagocitose de imunocomplexos nas espondiloartropatias soronegativas, lúpus eritematoso sistêmico e doença reumatóide.

Pathological samples (55) of serum selected from patients with Seronegative Spondylarthropathies, Systemic Lupus Erythematosus and Rheumatoid Disease were studied. The serum of all these patients showed negative rheumatoid factor by latex fixation reaction. The determination of the interference on the phagocytosis of gamma globulin aggregated by guinea pig's macrophages was obtained by one formula. The serum characterization was determined by selecting the ones that presented the most expressive results in the phagocytosis interference, by facilitation or inhibition. The results, in absolute and percentage values, showed the predominance of the interference phenomenon in phagocytosis, with significant statistical values (p < 0.05), when compared with normal serum. The comparative analysis among the diseases studied in the quantification of the serum interference in the phagocytosis of the immunocomplexes has not showed any significant difference. The phagocytosis inhibition occurred with more preponderance in the serum of patients with Reiter's Syndrome and Psoriatic Arthritis; in serum patients with Reiter's Syndrome there was a statistically significant difference in the inhibition of the phagocytosis (p = 0.0247). The serum characterization did not show that the serum fraction was responsible for the phagocytosis interference. In this stage it has been verified that there has not been an uniformity in the graphic curve of dilutions studied. The possibility of the existence of more than one element with interference in the phagocytosis of the studied immunocomplexes was mentioned.

Efficacy of auranofin as demonstrated by improvement in clinical parameters and decrease in anti-inflammatory usage: a long-term, multicenter study.

An open, noncomparative study at 8 rheumatology centers in Brazil assessed the efficacy and safety of auranofin (AF) when given for up to 24 months. The study enrolled 80 patients with classic or definite rheumatoid arthritis (RA); disease was severe in 20 (25%), moderate in 55 (69%), and mild in 5 (6%). Patients received auranofin, 3 mg twice daily, and varying doses of anti-inflammatory drugs (aspirin, nonsteroidal anti-inflammatory drugs, and corticosteroids). Sixty patients (75%) completed the full 24 months of therapy. No patients were withdrawn from therapy because of insufficient therapeutic effect. There was statistically significant improvement (p less than 0.001) in 9 clinical parameters of disease activity, evident as early as 3 months after beginning AF therapy, increasing steadily over 12 months, and remaining at improved levels for another 12 months. Improvements in some parameters were particularly striking. By 24 months, assessment of well-being had increased by 150%, intensity of pain had decreased by 66%, and duration of morning stiffness had decreased by 78%. The average daily dose of anti-inflammatory drugs also decreased over time. The safety profile of AF was similar to that found in comparable trials. Ten patients (12.5%) were withdrawn because of adverse events: 6 for diarrhea (7.5%), 2 for proteinuria (2.5%), and 1 each for pruritus and anemia (1.25%). Adverse events occurred in 24 of 80 patients; some reported more than one adverse event. The most common adverse events were loose stools (20 patients) or diarrhea (11 patients).(ABSTRACT TRUNCATED AT 250 WORDS)