Safety and efficacy of adalimumab treatment in Greek children with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile idiopathic arthritis (JIA). METHODS: Twenty-six patients were enrolled from January 2004 to January 2008 in this prospective observational study. Inclusion criteria were either unresponsiveness to disease-modifying anti-rheumatic drugs (DMARDs; n = 17) or to other anti-tumour necrosis factor (anti-TNF) agents (n = 9) or development of uveitis under other anti-TNFs (n = 2 of the 9). Efficacy was estimated using the American College of Rheumatology Pediatric (ACR Pedi) criteria. RESULTS: After 1-5 years of AD exposure, nine different adverse events (AEs) were recorded (12.6 AEs/100 patient-years), mainly mild respiratory tract infections and injection site-related reactions. Serious AEs (SAEs, 2.8/100 patient-years) were the development of abscess at the site of injection (n = 1) and lethal sepsis (n = 1). The ACR Pedi ≥ 30 responses for the first to the fifth year of treatment were 88.5, 57.7, 50.0, 34.6, and 11.5%, respectively. In total, 17 of the 26 (65.4%) patients responded to AD. Five of the 11 patients under steroids discontinued them 6 months post-treatment. Seven patients required weekly AD treatment to maintain remission and four of them benefited from this policy. Recurrent uveitis was hindered in three of the six patients, no new cases were recorded, and radiological regression was observed in two of the four patients with lesions. CONCLUSIONS: AD was safe and efficacious during the study period in the majority of patients. However, vigilance is required for the early detection of severe and potentially fatal infections. AD may control recurrent uveitis and radiological progression.

A follow-up study of patients with juvenile idiopathic arthritis who discontinued etanercept due to disease remission.

OBJECTIVES: Assessment of the post-etanercept (ET) disease course in patients with juvenile idiopathic arthritis (JIA) who discontinued the drug due to disease remission, using a recently developed tool that scores the disease activity. METHODS: Eleven patients (F/M 9/2, median age 9.2 years), with either a polyarthritis' (9) or an oligoarthritis' (2) disease course were followed up for 12.25-27 months after ET withdrawal. The median treatment period under ET was 36 months. The Juvenile Arthritis Disease Activity Score (JADAS) was used to grade the JIA activity at the time of ET commencement, at discontinuation and at the time of the flare. RESULTS: All 11 patients flared during the follow-up period. Compared to the time of ET initiation, JADAS was significantly reduced at ET discontinuation as well as at the time of the flare (26.3 to 0 and to 9.5 respectively, p<0.001). The median remission following ET discontinuation lasted 3 months. The flares were controlled with methotrexate±cyclosporine A in 10 patients and methotrexate plus anti-TNF in the remaining one. CONCLUSIONS: All patients after ET withdrawal flared but they had a minor disease activity score compared to the time of ET initiation. Flares were mostly controlled by the administration of 1 or 2 disease modifying anti-rheumatic drugs. JADAS was found to be a useful and handy tool for assessing and following-up the JIA activity over the disease course.

Persistent or severe course of reactive arthritis following Salmonella enteritidis infection. A prospective study of 9 cases.

During a 7 year-period 9 children (7 boys, 2 girls) with juvenile reactive arthritis (JReA) due to Salmonella enteritidis (Se) were prospectively studied because of an unusual type of onset and/or course of the disease. The mean duration of JReA activity was 9 +/- 3.6 months. The mean follow-up time was 55.2 +/- 17.4 months. JReA presented as any of the three types of juvenile chronic arthritis (JCA), namely, as asymmetrical oligoarthritis, polyarthritis, or systemic JCA in 5, 2, and 2 patients respectively. Two patients had pericarditis and three developed the complete or incomplete Reiter's syndrome during the disease or during a recurrence. Five patients carried the HLA-B27 and 3/5 developed psoriatic lesions 1 to 15 months after the onset of JReA. The presence of HLA-B27 and psoriasis was associated with a more prolonged course of JReA. However, no patient developed late radiological lesions or sacroiliitis during follow-up.

Prophylactic intravenous administration of immune globulin in preterm infants: effect on serum immunoglobulin concentrations during the first year of life.

In a prospective study, serum IgG, IgA, IgM, and IgG subclass levels of 66 preterm infants (gestational age less than or equal to 34 weeks) were measured sequentially from birth to 12 months of life. Infants were divided into two groups, comparable for gestational age, birth weight, sex, and intensive care, on the basis of admission order: the treatment group, consisting of 33 infants who received intravenous immune globulin therapy (0.5 gm/kg at 10-day intervals) prophylactically, and the control group, consisting of 33 infants who did not receive. Twenty of the 33 treated infants received only one infusion and the remaining 13 received two to five infusions. The mean number of infusions per neonate was 1.96. Immunoglobulin measurements showed that the proportion of infants with an IgG level of greater than or equal to 7 gm/L on the tenth and thirtieth days of life was significantly higher in the treatment than in the control group (p less than 0.01). At the same ages, mean serum IgG, IgG1, and IgG2 concentrations were significantly higher in the treatment group (p less than 0.001). Thereafter levels in both groups fell progressively, reaching their lowest point between 3 and 5 months of age. During this period, profound hypogammaglobulinemia (IgG less than 2 gm/L) was observed in 3 of 33 treated and 11 of 33 untreated infants (p less than 0.05). By 3 months of age, mean serum total IgG concentrations were still significantly higher in treated than in untreated infants (p less than 0.05), but the IgG subclass concentrations were not. After the third month, no significant differences between the two groups were observed. Moreover, the sequentially measured serum IgA and IgM levels in the two groups remained comparable from birth to age 12 months. The IgG level at different ages from 3 to 12 months was not correlated with either birth weight or the number of infusions performed during the neonatal period (p greater than 0.1). We conclude that prophylactic intravenous administration of immune globulin to preterm infants with a birth weight of 1000 to 2000 gm, at a dose of 0.5 gm/kg every 10 days, results in maintenance of a satisfactory serum IgG level throughout the high-risk period for infections. Such treatment does not have a suppressive effect on subsequent serum immunoglobulin concentrations.

Iron-related disturbances of cell-mediated immunity in multitransfused children with thalassemia major.

Immunological abnormalities have been observed in many haemophiliacs receiving clotting factor concentrates. To determine whether similar changes also occur after repeated blood transfusions we estimated T cell subsets and cutaneous delayed hypersensitivity (CDH) in 50 multitransfused children with beta-thalassemia major (beta-TM). All patients were also tested for anti-HTLV-III/LAV antibodies. A diminished percentage of T lymphocytes (E-rosettes, T3+), and T4+ cells and a low T4/T8 ratio was found in patients as compared to age and sex matched controls (P less than 0.001). Negative CDH tests to specific antigens (Multi-test) were also found in a significantly larger proportion of beta-TM children (P less than 0.01). Antibodies against HTLV-III/LAV were negative in all patients. Decreased T4/T8 ratio in beta-TM children was primarily due to a reduction of T4+ cells and was inversely correlated to the patients' age, number of units of transfused blood (P less than 0.05) and especially to ferritin serum levels and annual iron balance (P less than 0.001). These findings indicate that immunological abnormalities in beta-TM patients appear to be acquired, transfusion-associated and related to iron load which depends on the appropriate chelation therapy.