Rheumatoid Arthritis: Balogh Z

Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, Wouters C, Silverman ED, Balogh Z, Henrickson M, Apaz MT, Baildam E, Fasth A, Gerloni V, Lahdenne P, Prieur AM, Ravelli A, Saurenmann RK, Gamir ML, Wulffraat N, Marodi L, Petty RE, Joos R, Zulian F, McCurdy D, Myones BL, Nagy K, Reuman P, Szer I, Travers S, Beutler A, Keenan G, Clark J, Visvanathan S, Fasanmade A, Raychaudhuri A, Mendelsohn A, Martini A, Giannini EH, Anonymous00187, Anonymous00188. · IRCCS, Istituto G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17763439 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. RESULTS: Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. CONCLUSION: While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.

Ruperto N, Ravelli A, Castell E, Gerloni V, Haefner R, Malattia C, Kanakoudi-Tsakalidou F, Nielsen S, Bohnsack J, Gibbas D, Rennebohm R, Voygioyka O, Balogh Z, Lepore L, Macejkova E, Wulffraat N, Oliveira S, Russo R, Buoncompagni A, Hilário MO, Alpigiani MG, Passo M, Lovell DJ, Merino R, Martini A, Giannini EH, Anonymous00431, Anonymous00432. · IRCCS G. Gaslini, Pediatria II-Reumatologia, PRINTO, Genova, Italy. · Clin Exp Rheumatol. · Pubmed #17181934 No free full text.

Abstract: OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Gergely P, Pazár B, Nagy ZB, Gombos T, Rajczy K, Balogh Z, Orbán I, Sevcic K, Poór G. · 1st Department of Rheumatology, National Institute of Rheumatology and Physiotherapy, Frankel Leó u. 25-29, Budapest, H-1023 Hungary. · J Rheumatol. · Pubmed #19286845 No free full text.

Abstract: OBJECTIVE: To investigate the possible association between polymorphisms of the mannose-binding lectin gene (MBL2) and susceptibility to juvenile idiopathic arthritis (JIA). METHODS: We performed a case-control association study including 118 Hungarian patients with JIA and 118 sex-matched healthy controls. MBL genotyping for the 3 mutant structural alleles at codons 54 (B), 57 (C), and 52 (D) in exon 1 and the promoter polymorphisms at position -550 (HL) and -221 (YX) were carried out by real-time PCR allelic discrimination. Serum level of MBL was determined by ELISA. RESULTS: Variant allele frequencies of both codon 52 and 57 polymorphisms in the MBL2 gene were significantly overrepresented in JIA (p=0.001 and p=0.004, respectively). The frequency of low MBL genotypes (XA/XA, YA/YO, XA/YO, and YO/YO) in JIA was higher than that in healthy controls (p=0.001). Serum MBL concentrations were found to be significantly lower in JIA patients versus control subjects (p=0.001). The 2 promoter polymorphisms and codon 54 SNP of the MBL2 gene were not associated with JIA. CONCLUSION: Our findings suggest that genetically determined low MBL levels may predispose children to JIA in a Hungarian population. These data warrant further research to investigate the role of the lectin-dependent complement system in the pathogenesis of JIA.

Pazár B, Gergely P, Nagy ZB, Gombos T, Pozsonyi E, Rajczy K, Balogh Z, Sevcic K, Orbán I, Szodoray P, Poór G. · National Institute of Rheumatology and Physiotherapy, Budapest, Hungary. · Clin Exp Rheumatol. · Pubmed #19210888 No free full text.

Abstract: OBJECTIVE:Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS:A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS:In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS:Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA.

Gutiérrez-Suárez R, Pistorio A, Cespedes Cruz A, Norambuena X, Flato B, Rumba I, Harjacek M, Nielsen S, Susic G, Mihaylova D, Huemer C, Melo-Gomes J, Andersson-Gare B, Balogh Z, De Cunto C, Vesely R, Pagava K, Romicka AM, Burgos-Vargas R, Martini A, Ruperto N, Anonymous00034. · IRCCS G. Gaslini, Università di Genova, Pediatria II - Reumatologia, Largo Gaslini, 5 16147 Genova, Italy. · Rheumatology (Oxford). · Pubmed #16877459 links to  free full text

Abstract: OBJECTIVES: To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas. METHODS: The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in Western Europe; 10 in Eastern Europe; and four in Latin America. Potential determinants of poor HRQL included demographic data, physician's and parent's global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children. RESULTS: A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain. CONCLUSION: We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin.

Orban I, Ruperto N, Balogh Z, Anonymous00070. · National Institute of Rheumatology and Physiotherapy, Budapest, Hungary. · Clin Exp Rheumatol. · Pubmed #11510337 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Hungarian 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 Hungarian CHAQ CHQ were fully validated with 3 forward and 3 backward translations. A total of 127 subjects were enrolled: 67 patients with JIA (13.5% systemic onset, 42% polyarticular onset, 13.5% extended oligoarticular subtype, and 31% persistent oligoarticular subtype) and 60 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 Hungarian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Rojkovich B, Poór G, Koó E, Mikó I, Orbán I, Balogh Z, Gömör B, Szabó LZ. · Országos Reumatológiai és Fizioterápiás Intézet, Budapest. · Orv Hetil. · Pubmed #10934883 No free full text.

Abstract: Relapsing polychondritis is a relatively rare disease characterized by episodic inflammation and progressive destruction of cartilage involving ears, nasal and laryngotracheal cartilage, cardiovascular system and the eyes. The increasing awareness of its clinically distinct has resulted in recognition of at least 550 reported cases. Six cases are reported to demonstrate the wide variety of clinical pattern. The most common features of the disease are auricular and nasal cartilage inflammation and nondeforming arthritis. Ocular symptoms and vasculitis is relatively rare. Two cases of relapsing polychondritis with laryngotracheobronchial manifestations illustrate the severe clinical features of the disease. Relapsing polychondritis may associate with diverse forms of connective tissue disease, such as rheumatoid arthritis. It seems interesting to note the onset in childhood. Treatment has been primarily symptomatic. In situations of mild symptoms, initial treatment is with nonsteroidal antiinflammatory drugs. For cases with serious manifestation, corticosteroids and immunosuppressants are indicated.