Rheumatoid Arthritis: Jarosová K

Pavelka K, Jarosová K, Suchý D, Senolt L, Chroust K, Dusek L, Vencovský J. · Institute of Rheumatology, Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Ann Rheum Dis. · Pubmed #19351624 No free full text.

Abstract: OBJECTIVE: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. METHODS: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease >1.2) but who were not in remission (DAS28 >2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). RESULTS: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). CONCLUSIONS: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.

Pavelka K, Gatterová J, Tegzová D, Jarosová K, Tomasová Studýnková J, Svobodník A, Svihálek J, Dusek L, Vencovský J. · Institute of Rheumatology and Department of Rheumatology, Charles University, Prague, Czech Republic. · Clin Exp Rheumatol. · Pubmed #17888209 No free full text.

Abstract: OBJECTIVE: To evaluate the clinical status and radiographic progression in patients with rheumatoid arthritis (RA) being followed by the Czech National Registry of biological treatments. METHODS: Patients who failed at least two disease-modifying antirheumatic drugs and had high disease activity (DAS28 > 5.1) were treated with infliximab. Radiographic progression was measured with a modified version of the Sharp score (TSS) after 54 weeks of treatment. RESULTS: Ninety-nine patients with an average disease duration of 13.7 years were enrolled. The DAS28 dropped from 6.66 to 4.07 (p < 0.001). Before treatment the mean TSS was 90.1 and the mean estimated yearly disease progression was 8.56. After 54 weeks of infliximab, radiographic progression was 4.15 times slower than the estimated rate before treatment and 63 patients did not show any radiographic progression at all. In the remaining 36 patients, the progression rate slowed to 3.8 +/- 0.9 from the estimated TSS of 10.9 +/- 6.9 before the initiation of treatment (p = 0.011). CONCLUSION: Data derived from the Czech National Registry, which reflect general clinical practice, show a significant retardation of radiographic progression in patients treated with anti-TNF and the magnitude of the improvement seen is similar to results from clinical trials.

Vencovský J, Jarosová K, Růzicková S, Nemcová D, Niederlová J, Ozen S, Alikasifoglu M, Bakkaloglu A, Ollier WE, Mageed RA. · Institute of Rheumatology, Prague, Czech Republic. · Arthritis Rheum. · Pubmed #11665981 No free full text.

Abstract: OBJECTIVE: An increased incidence of allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) in several inflammatory diseases has recently been reported. The aim of this study was to examine a variable number tandem repeat (VNTR) polymorphism of the IL1RN gene in patients with juvenile idiopathic arthritis (JIA). METHODS: Findings in 185 Czech patients with JIA were compared with those in 168 Czech controls, 50 JIA patients and 52 controls of Turkish origin, and 79 controls from central England. VNTR polymorphism analysis of IL1RN was performed by polymerase chain reaction using 2 flanking primers to amplify an 86-bp tandem repeat region in intron 2. RESULTS: The frequency and carriage rate of IL1RN*2 were significantly increased in Czech JIA patients compared with the Czech controls (frequency 27.6% versus 15.8%; carriage rate 44.3% versus 26.2%). Increased frequency and carriage rate of IL1RN*2 were found in 23.3% and 40.0% of Turkish JIA patients and in 17.3% and 34.6% of ethnically matched controls. The high representation of IL1RN*2 in 52.3% of the 22 patients with extended oligoarthritis, 31.3% of the 56 patients with enthesitis-related arthritis, and 42.9% of the 14 patients with other arthritis was particularly responsible for the increased frequency of IL1RN*2 in the Czech JIA patients. We found no association of IL1RN*2 with disease activity or severity parameters. CONCLUSION: Inheritance of IL1RN*2 may contribute to genetic susceptibility in several forms of autoimmune diseases, including JIA. The IL1RN*2 allele may be useful as a prognostic indicator of the evolution of an extended oligoarticular course of JIA.