Rheumatoid Arthritis: Lupi E

Gerloni V, Pontikaki I, Gattinara M, Desiati F, Lupi E, Lurati A, Salmaso A, Fantini F. · Istituto G. Pini, Milan, Italy. <> · Arthritis Rheum. · Pubmed #15693004 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (infliximab) with methotrexate (MTX) in juvenile idiopathic arthritis (JIA) with an active polyarticular course that is not responsive to MTX. METHODS: Twenty-four young adults with long-lasting, refractory JIA were enrolled in an open, prospective, 2-year pilot study. Patients received intravenous infliximab at 3 mg/kg of body weight at weeks 0, 2, and 6 and every 8 weeks thereafter, with weekly subcutaneous MTX. RESULTS: The median duration of therapy was 9.1 months. Significant improvements were observed in the number of joints (28-joint count) with active disease (median 6 at baseline, 2 at 2 weeks, 0 at 6 months, 0 at 1 year; P < 0.05). Pain as well as patient's and physician's global assessments of disease status were assessed on 0-100-mm (0 = best; 100 = worst) visual analog scales (VAS). There were significant improvements in VAS pain scores (45 at baseline, 25 at 2 weeks, 8.5 at 6 months, 10 at 1 year; P < 0.05), patient's global assessment of disease status (50 at baseline, 22 at 2 weeks, 11.5 at 6 months, 18 at 1 year; P < 0.05), and physician's global assessment of disease status (50.5 at baseline, 22.5 at 2 weeks, 6.5 at 6 months, 10 at 1 year; P < 0.01). In addition, there were significant improvements in the erythrocyte sedimentation rate (64 mm/hour at baseline, 36 mm/hour at 2 weeks, 23.5 mm/hour at 6 months, 35 mm/hour at 1 year; P < 0.01) and C-reactive protein level (4.9 mg/dl at baseline, 2.8 mg/dl at 2 weeks, 3.1 mg/dl at 6 months, 3.2 mg/dl at 1 year; P < 0.005). The percentage of patients meeting the American College of Rheumatology 20% improvement criteria at each assessment ranged from 54.2% to 86.7%. Of the responses on the Disease Activity Score in 28 joints, 37.5-63.6% were classified as "good," 14.3-33.3% were classified as "moderate," and 18-37.5% were classified as "no response." Twelve patients (50%) had adverse events, and 5 patients (20.8%) withdrew. CONCLUSION: Infliximab plus MTX showed high effectiveness and safety in short- and medium-term treatment of long-lasting refractory JIA. A controlled multicenter clinical trial is needed.

Ingegnoli F, Del Papa N, Comina DP, Maglione W, Lupi E, Gerloni V, Fantini F. · Department of Rheumatology, University of Milan, Istituto Ortopedico Gaetano Pini, Milan, Italy. · Clin Exp Rheumatol. · Pubmed #15301253 No free full text.

Abstract: OBJECTIVE: To determine the prevalence of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA) and to assess any association between the presence of anti-chromatin Abs and clinical subsets of the disease. METHODS: IgG anti-chromatin Abs and anti-extractable nuclear antigens (ENA) Abs were detected by an enzyme-linked immunosorbent assay (ELISA), and antinuclear Abs (ANA) by indirect immunofluorescence in sera of 89 children with JRA. Ten children with systemic, 32 with polyarticular and 47 with pauciarticular disease onset (uveitis occurred in 17/47 children) were studied. As a control group, 12 sera of patients suffering from idiopathic uveitis and 31 age- and-sex-matched healthy children (HC) were examined. RESULTS: Abs to chromatin were detected in 14/47 (29.8%) of children suffering from pauciarticular onset JRA and in this group the higher prevalence of anti-chromatin Abs has been found in children with chronic uveitis (p = 0.002). Anti-chromatin positivity was observed in 2/10 (20%) of systemic and in 3/32 (9.3%) of polyarticular onset JRA. Furthermore, none of the patients with idiopathic uveitis and HC had Abs to chromatin. anti-chromatin Abs titers remained relatively stable over a 6-month control period. CONCLUSION: Our results confirm previous data about the presence of circulating anti-chromatin Abs in juvenile arthritis. Interestingly, anti-chromatin Abs were significantly higher in the group of patients with pauciarticular onset with past or present history of uveitis, than in patients without ocular involvement. A long-term follow-up study could be useful to demonstrate the potential utility of these autoantibodies in diagnosing, classifying and treating children affected.

Ingegnoli F, Del Papa N, Lupi E, Comina DP, Maglione W, Gerloni V, Fantini F. · Cattedra di Reumatologia, Istituto Gaetano Pini, Milano, Italia. · Reumatismo. · Pubmed #14872223 links to  free full text

Abstract: OBJECTIVE: to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). METHODS: IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. RESULTS: Abs to chromatin were detected in 24/94 (25.5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23.7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21.7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNF-alpha therapy (p< 0.0001). CONCLUSIONS: our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present history of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies.

Fantini F, Gerloni V, Gattinara M, Cimaz R, Arnoldi C, Lupi E. · Institute of Rheumatology, Milano, Italy. · J Rheumatol. · Pubmed #12610820 No free full text.

Abstract: OBJECTIVE: As continuity of care in our institution allows longterm followup studies, we reviewed the files of all consecutive patients with juvenile chronic (idiopathic) arthritis (JCA) followed since 1970 to establish the frequency of remission. METHODS: Charts of all patients with JCA were reviewed. Relevant variables were entered into a customized database. The presence of remission (lack of signs of disease activity in the absence of antirheumatic therapy for at least 6 mo) during the disease course and at the last visit was assessed. RESULTS: The cohort included 683 patients, 463 females and 220 males. According to the disease onset, 420 had oligoarticular, 108 polyarticular (23 rheumatoid factor positive), and 88 systemic disease; 67 had a juvenile spondyloarthropathy (SpA). For all 4 categories the mean followup period was about 10 years. At the last visit 224 cases were in remission (32.8%). Remission rate was scarcely influenced by age at disease onset, but differed in the different disease categories. Of the total group of 683 patients, 153 (22.4%) were lost to followup (no control for at least 2 years). For all 4 categories the remission rate at the last visit was higher in patients who had been lost to followup: 42.3% versus 29.0% for systemic onset JCA, 20.8% versus 16.5% for polyarticular onset JCA, 44.7% versus 33.6% for pauciarticular onset JCA, and 66.7% versus 26.8% for juvenile SpA. The probability of attaining remission decreased in proportion to delay in entering the tertiary care center (from 35.7% to 22.8%). The rate of remission reached its peak after 5-10 years of followup, after which the trend reversed. CONCLUSION: Childhood arthritis achieved remission in only about one-third of our cases, with differences among disease categories based on the diagnosis.