Rheumatoid Arthritis: Corona F

Ruperto N, Murray KJ, Gerloni V, Wulffraat N, de Oliveira SK, Falcini F, Dolezalova P, Alessio M, Burgos-Vargas R, Corona F, Vesely R, Foster H, Davidson J, Zulian F, Asplin L, Baildam E, Consuegra JG, Ozdogan H, Saurenmann R, Joos R, Pistorio A, Woo P, Martini A, Anonymous00439. · IRCCS G. Gaslini, University of Genoa, Genoa, Italy. · Arthritis Rheum. · Pubmed #15248217 links to  free full text

Abstract: OBJECTIVE: To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m(2)/week) versus a higher dosage (30 mg/m(2)/week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/week). METHODS: In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively). RESULTS: In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups. CONCLUSION: This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m(2)/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate its full therapeutic effect.

Nielsen S, Ruperto N, Gerloni V, Simonini G, Cortis E, Lepore L, Alpigiani MG, Zulian F, Corona F, Alessio M, Barcellona R, Gallizzi R, Rossi F, Magni-Manzoni S, Lombardini G, Filocamo G, Raschetti R, Martini A, Ravelli A, Anonymous00024. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genova, Italy. · Clin Exp Rheumatol. · Pubmed #18799107 No free full text.

Abstract: OBJECTIVE: To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS: Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. RESULTS: A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION: Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.

Dell'Era L, Facchini R, Corona F. · Clinica Pediatrica De Marchi, University of Milan, Milan, Italy. · J Pediatr Orthop B. · Pubmed #18391810 No free full text.

Abstract: The purpose of the study was to assess the outcomes of knee synovectomies in children with juvenile idiopathic arthritis. Thirty-one arthroscopic synovectomies were performed in 19 children (six oligoarthritis, 20 polyarthritis, five psoriatic arthritis). The percentage of recurrence in the group with oligoarthritis was 67%, in the group with polyarthritis was 95%, whereas all psoriatic arthritis recurred. The overall mean survival (i.e. free from recurrence) was 1.05 years (95% confidence interval, 0.74-1.35). Mean survival time was 1.69, 0.80 and 1.30 years, respectively, for oligoarthritis, polyarthritis and psoriatic arthritis. After synovectomy we observed two complications: thrombophlebitis of the omolateral superior femoral vein and septic arthritis. In conclusion, the mainstay of therapy for juvenile idiopathic arthritis remains medical treatment and intensive physiotherapy. The aim of arthroscopic synovectomy is to allow to make the most of nonsurgical therapy. It revealed more accurate and less invasive results than open synovectomy, maintained the range of motion of the joint, allowed early mobilization and required shorter hospitalization. Best results were observed in the group of oligoarthritis.

Dell'Era L, Vercellesi P, Forzenigo LV, Carnelli V, Corona F. · Pediatric Rheumatologic Centre, II Pediatric Clinic, Fondazione Policlinico, Mangiagalli e Regina Elena, Milan, Italy. · Clin Rheumatol. · Pubmed #18330610 No free full text.

Abstract: Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis.

Grassi A, Corona F, Casellato A, Carnelli V, Bardare M. · Pediatric Rheumatology Centre, Clinica Pediatrica De Marchi, Milan, Italy. · J Rheumatol. · Pubmed #17343317 No free full text.

Abstract: OBJECTIVE: To determine prevalence and complications of juvenile idiopathic arthritis (JIA)-associated uveitis, and to evaluate risk factors for uveitis and its relation to articular disease. METHODS: Records of 309 patients with JIA (244 female, 65 male, mean age at onset 4.9 yrs) were retrospectively reviewed. Occurrence of uveitis and complications were assessed among oligoarticular-onset JIA (193 patients), polyarticular-onset JIA (66 patients), and systemic-onset JIA (50 patients). The presence of antinuclear antibodies (ANA) was determined in patients with oligoarticular-onset JIA. Therapy and relapses of uveitis and arthritis were recorded at each visit during the followup (mean followup 7.6 yrs). RESULTS: Sixty-two patients developed uveitis (20.1%); 57 patients had oligoarticular-, 3 polyarticular-, and 2 systemic-onset JIA. Uveitis was asymptomatic in 56/62 cases. Fifty-five of the 62 patients (88.7%) developed uveitis within 4 years from disease onset. In patients with oligoarticular-onset JIA, an early age at disease onset and the presence of ANA (p < 0.05) and DRB1*11 (p < 0.03) were the best predictors of uveitis, while a polyarticular course was not associated to uveitis (p > 0.05). Active arthritis was present at the first episode of uveitis in 46/62 patients. Forty-four of the 62 patients experienced relapses of uveitis: in 20/62, relapses were concomitant to arthritis relapses; in 24/62 relapses presented without active arthritis. Complications of uveitis developed in 35.5% of the patients (22/62), leading to visual impairment in 13 patients. CONCLUSION: Current guidelines provide early identification of uveitis in 90% of patients. With the exception of the first episode of uveitis, uveitis and arthritis seem to run different courses; close ophthalmologic scrutiny then should also be maintained during arthritis remission.

Rusconi R, Corona F, Grassi A, Carnelli V. · Unit of Endocrinology, University of Milan, Italy. · J Pediatr Endocrinol Metab. · Pubmed #12729405 No free full text.

Abstract: OBJECTIVE: To study the effect on the timing of menarche of the different subtypes of juvenile rheumatoid arthritis (JCA) and their therapies. METHODS: Auxological data (including the age at menarche of themselves and their mothers) were collected from 83 females regularly attending our rheumatological unit. Malnourished patients were excluded from the study. The patients were divided into groups on the basis of disease subtype and glucocorticoid (GC) therapy. RESULTS: The timing of menarche was later in all the patients in comparison with their mothers and normal Italian girls, and those who had taken GC had a later menarche and less pubertal growth than those who had not. The girls with systemic JCA had a later menarche than those with the polyarticular or pauciarticular subtypes. CONCLUSIONS: Our results show that pubertal development is compromised in girls with JCA, particularly if they have received GC therapy.

Ruperto N, Ravelli A, Pistorio A, Malattia C, Viola S, Cavuto S, Alessio M, Alpigiani MG, Buoncompagni A, Corona F, Cortis E, Falcini F, Gerloni V, Lepore L, Sardella ML, Strano CG, Zulian F, Gado-West L, Tortorelli A, Fantini F, Martini A, Anonymous00072. · Laboratorio di Informatica Medica, IRCCS S. Matteo, Università di Pavia, Italy. · Clin Exp Rheumatol. · Pubmed #11510339 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Italian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Italian CHAQ was already published in the literature and was therefore revalidated while the Italian CHQ was fully cross culturally adapted with 3 forward and 3 backward translations, and than validated. A total of 1,192 subjects were enrolled: 404 patients with JIA (16% systemic onset, 31% polyarticular onset, 21% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 788 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Italian version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

Bianchi ML, Cimaz R, Galbiati E, Corona F, Cherubini R, Bardare M. · Centro Metabolismo Minerale e Osseo, Divisione Endocrinologia, Istituto Auxologico Italiano IRCCS, Milan, Italy. · Osteoporos Int. · Pubmed #10501775 No free full text.

Abstract: Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA.