Rheumatoid Arthritis: Szechiński J

Swierkot J, Szechiński J. · Department of Rheumatology, Medical University of Wrocław, Wiśniowa 36, PL 51-137 Wrocław, Poland. · Pharmacol Rep. · Pubmed #16963793 links to  free full text

Abstract: A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue of folic acid and of aminopterin, is the most commonly used DMARD and is now prescribed worldwide to at least 500,000 patients with RA. The mechanism by which MTX used at a low dose modulates inflammation in RA is still unknown. Monitoring of the therapy in terms of MTX concentration in patients with RA seems not to have a significant influence on the effectiveness of the treatment. Two meta-analyses showed that MTX has one of the best efficacy/toxicity ratios. It should be the first DMARD used in the majority of patients with RA at this time. However, a significant number of patients treated only with MTX fail to achieve optimal disease control, so there are many combinations of DMARD regimes. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission. The therapy of RA is a dynamic process and requires maintaining a delicate balance between benefits and risks. Even with the newer biological agents, MTX continues to serve as a reference point and there is still a role for MTX in the treatment of RA patients.

Szmyrka-Kaczmarek M, Dziemianko I, Szechiński J. · Zakład Reumatologii AM we Wrocławiu. · Pol Arch Med Wewn. · Pubmed #14682232 No free full text.

This publication has no abstract.

Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechiński J, Li T, Teng J, Becker JC, Westhovens R. · Center for Rheumatology, Albany Medical College, Albany, New York 12206, USA. · Arthritis Rheum. · Pubmed #18383390 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy, radiographic changes, and safety of abatacept and methotrexate therapy through 2 years in a long-term extension of a previously published 1-year study. METHODS: Patients who received placebo during year 1 were switched to abatacept. Patients taking abatacept continued to take it. Efficacy and safety were assessed through 2 years. RESULTS: Of 539 patients enrolled in the initial 1-year study, 488 completed 1 year of the long-term extension (2% discontinued for lack of efficacy). At 2 years, patients taking abatacept had maintained their responses on the American College of Rheumatology (ACR) improvement criteria and the Disease Activity Score in 28 joints (DAS28; using the C-reactive protein [CRP] level), as well as their physical function (according to the Health Assessment Questionnaire [HAQ] disability index [DI]) and health-related quality of life (HRQOL; assessed with the Short Form 36 [SF-36] health survey), that were observed at the end of the double-blind period (year 1 versus year 2 values were 81.9% versus 80.3% for ACR 20% improvement, 25.4% versus 30.9% for a DAS28 [CRP] of <2.6, 71.8% versus 66.8% for the HAQ DI, and 9.7 versus 10.6 and 7.3 versus 7.2, respectively, for the mean change in the physical and mental components summary scores of the SF-36). In the abatacept group, post hoc analysis demonstrated further inhibition of radiographic progression during year 2 (57% reduction in mean change of total score in year 2 versus year 1; P<0.0001), and minimal radiographic progression was observed (mean change in total score from baseline was 1.1 and 1.6 at year 1 and 2, respectively). Rates of adverse events (AEs) and severe AEs were consistent throughout the cumulative period. CONCLUSION: The improvements in signs and symptoms, physical function, and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of treatment. This durability was accompanied by a safety profile consistent with that in the double-blind portion of the study. Radiographic progression was further inhibited in year 2 compared with year 1, suggesting an increasing effect of abatacept on the inhibition of structural damage in year 2.

Wiland P, Głowska A, Chlebicki A, Szechiński J. · Oddział Chorób Wewnetrznych i Reumatologii Okregowego Szpitala Kolejowe, Wrocławiu. · Pol Arch Med Wewn. · Pubmed #12685246 No free full text.

Abstract: The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal antibody (Remicade) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis (RA). We investigate also the interval necessary to obtain the improvement in both treatment groups. 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0, 4, 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab, anti-TNF-alfa monoclonal antibody (Remicade) and methotrexate at a stable dose. Patients were assessed by composite clinical score (DAS 28) and C-reactive protein during 22 weeks of therapy. At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity. At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91% of infliximab-treated patients and 58% gold treated patients (p < 0.001). Adverse events were more frequently observed in infliximab-treated patients, but only gold-treated patients discontinued treatment because adverse events (2 patients due to proteinuria, 2 patients due to mucocutaneous changes and one patient due to leucopenia). The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions (23 reactions out of 160 infusions); most of them were mild (somnolentia and headache) and transient. Viral infections (including herpes simplex and zoster) were more common in patients treated with infliximab and methotrexate. Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment, especially in the first 6 weeks.

Swierkot J, Szechiński J, Wiland P. · Zakład Reumatologii Akademii Medycznej we Wrocławiu. · Pol Arch Med Wewn. · Pubmed #11291608 No free full text.

Abstract: The objective of this study was to determine long term efficacy and safety of low dose methotrexate (MTX) in treatment of rheumatoid arthritis (RA). Thirty patients receiving MTX for RA were prospectively studied over a mean treatment period of 60 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 24, and 60 months. The occurrence of adverse reactions was noted. Initially MTX was given orally 7.5 mg once a week. In the course of the observation the dose ranged between 5 and 15 mg/week. 13 patients (43%) completed 5-years study. Treatment with MTX was stopped due to adverse events in 4 cases, inefficacy in 7 patients, poor compliance and fear of toxicity in 3 patients and death in 3 patients. The factors related to their death were unrelated in all 3 cases to study MTX therapy. In 13 patients who completed 60 months of therapy, a significant improvement was noted comparing to baseline in 9 out of 12 clinical disease variables and acute phase reactants. There was also a significant decrease in the mean daily dosage of NSAIDs. Adverse events occurred in 64% of the patients, but only 13% of the patients discontinued MTX permanently. The side effects occurred more often in older patients. RA patients treated for five years with MTX showed statistically significant clinical improvement and decrease of inflammation parameters. MTX treatment may be helpful also in patients with advanced forms of RA.

Wiland P, Szechiński J. · Institute of Rheumatology, Medical Academy and PKP Hospital, Wrocław, Poland. · Clin Rheumatol. · Pubmed #10357114 No free full text.

Abstract: The purpose of the study was to determine the effect of initiation of gold therapy on glomerular and tubular integrity. Urine albumin was used as a marker of glomerular damage. N-acetyl-beta-D-glucosaminidase (NAG) urinary excretion served as an indicator of proximal tubular damage. This study was an adjunct to a clinical trial that investigated the safety and the efficacy of Depo-Medrone during the induction phase of gold therapy. The NAG activities and albumin levels in the urine of 36 patients with active rheumatoid arthritis treated with sodium aurothiomalate weekly up to a total of 1 g were investigated. NAG was assayed in 565 early morning urine samples of these patients at weekly intervals for 24 weeks. The mean NAG level rose from 50.2 nmol/mg of creatinine on entry to peak NAG excretion of 120.4 nmol/mg of creatinine at week 4 and then fell to 56.3 nmol/mg of creatinine at week 24. Urinary albumin was assayed in 252 early morning urine samples at monthly intervals during gold treatment. Values greater than 20 mg/l were observed in 7.5% of urine samples. Microalbuminuria was present in 9% of patients at baseline. Two patients who were withdrawn because of proteinuria and macroalbuminuria had normoalbuminuria on entry. We conclude that raised levels of NAG associated with tubular damage are more frequent than glomerular damage on entry to, and during, treatment with gold salts.

Nowak B, Kowalski M, Maczyrńska B, Szechiński J, Przondo-Mordarska A. · Zakład Reumatologii Akademii Medycznej we Wrocławiu. · Pol Arch Med Wewn. · Pubmed #18468425 No free full text.

Abstract: OBJECTIVES: The pathogenesis of seronegative spondyloarthropathies is still unknown. A microbial etiology has been suggested. The aim of the study was to analyze the antibodies against Klebsiella O-antigens in serum of patients with seronegative spondyloarthropathies. METHODS: 30 patients with seronegative spondyloarthropathies, 20 with rheumatoid arthritis and 20 healthy volunteers were included in the study. The serum antibodies against Klebsiella O1 and O3 antigens were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In serum of patients with seronegative spondyloarthropaties the antibodies against Klebsiella antigen O1 and O3 occur less frequently (6.67%) than in serum of patients with rheumatoid arthritis (35%) and that in serum of healthy subjects (40%). CONCLUSIONS: The results do not confirm the role of LPS in the pathogenesis of seronegative spondyloarthropthies, but on the other hand we could not exclude the concept that it may play an important role.

Przybysz M, Maszczak D, Borysewicz K, Szechiński J, Katnik-Prastowska I. · Department of Chemistry and Immunochemistry, Wrocław Medical University, Bujwida 44a, 50-345, Wrocław, Poland. · Glycoconj J. · Pubmed #17610063 No free full text.

Abstract: The expressions of terminal sugars in synovial and plasma fibronectins were studied in relation to rheumatoid arthritis (RA) progression defined according to the early, established and late radiological changes in the patients' hands. The relative amounts of sialic acid and fucose were analyzed by lectin-ELISA using appropriate sialic acid-linked alpha2-3 (Maackia amurensis) and alpha2-6 (Sambucus nigra) lectins as well as fucose-linked alpha1-6 (Aleuria aurantia), alpha1-2 (Ulex europaeus), and alpha1-3 (Tetragonolobus purpureus). In the early RA group, the synovial fibronectin reactivities were the lowest with the all lectins used. In the established and late groups, relative sialylation and fucosylation significantly increased. However, sialylation negligibly decreased, whereas fucosylation remained at nearly the same level in the late group. Moreover, the expression of alpha1-6-linked fucose was found to be related to disease activity. In contrast, plasma fibronectin reactivity with lectins showed different dynamic alterations. In the early RA group, the reactivity of fibronectin with the lectins used was similar to that of healthy individuals, whereas it increased significantly in the established RA group compared with the early and normal plasma groups. In the late RA group it decreased to a level similar to that of the normal group. The lower expressions of terminal sugars in synovial fibronectin were mainly associated with the early degenerative processes of RA. In conclusion, such alterations may be applicable as a stage-specific marker for diagnosis and therapy of RA patients. The higher expression of terminal sugars in fibronectin could be associated with repair and adaptation processes in longstanding disease.

Pasek M, Duk M, Podbielska M, Sokolik R, Szechiński J, Lisowska E, Krotkiewski H. · Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wroclaw, Poland. · Glycoconj J. · Pubmed #17006638 No free full text.

Abstract: It is well documented that serum IgG from rheumatoid arthritis (RA) patients exhibits decreased galactosylation of its conservative N-glycans (Asn-297) in CH2 domains of the heavy chains; it has been shown that this agalactosylation is proportional to disease severity. In the present investigation we analyzed galactosylation of IgG derived from the patients using a modified ELISA-plate test, biosensor BIAcore and total sugar analysis (GC-MS). For ELISA and BIAcore the binding of IgG preparations, purified from the patients' sera, to two lectins: Ricinus communis (RCA-I) and Griffonia simplicifolia (GSL-II) was applied. Based on ELISA-plate test an agalactosylation factor (AF, a relative ratio of GSL-II/RCA-I binding) was calculated, which was proportional to actual disease severity. Repeated testing of several patients before and after treatment with methotrexate (MTX) alone or in combination with Remicade (a chimeric antibody anti-TNF-alpha) supplied results indicating an increase of IgG galactosylation during the treatment. This introductory observation suggests that IgG galactosylation may be an additional indicator of the RA patients' improvement.

Wiland P, Wiela-Hojeńska A, Swierkot J, Hurkacz M, Orzechowska-Juzwenko K, Szechiński J. · Oddział Chorób Wewnetrznych i Reumatologii, Okregowy Szpital Kolejowy we Wrocławiu. · Pol Arch Med Wewn. · Pubmed #14682224 No free full text.

Abstract: BACKGROUND: The elevation of N-acetyl-beta-D-glucosaminidase (NAG) in urine has been shown to be associated with reversible renal tubular damage. OBJECTIVES: The aim of the study was to examine the effect of first oral low dose methotrexate (MTX) on urinary excretion of NAG comparing with MTX concentration in serum and urine in a cohort of patients with rheumatoid arthritis (RA). METHODS: Urinary NAG to urinary creatinine ratio (NAG index) determined in 43 patients (5 males, 38 females) with RA who started taking the first oral dose of 10 mg of MTX. Urinary NAG index was observed at 24 h and 48 h after the first MTX dose. MTX concentration was measured in blood at 90 minutes and in blood and urine at 24 h after the drug administration. RESULTS: NAG-enzymuria was increased in 72.1% of the patients before administration of MTX therapy (10.8 UI/g creatinine). There was no change in NAG index at 24 and 48 h after first dose of MTX (9.1 and 10.7 UI/g of creatinine). No differences of NAG-enzymuria in non-steroidal anti-inflammatory drug (NSAID)-treated patients and NSAID-free patients before and after MTX administration were revealed. The patients with decreased creatinine clearance had before treatment higher NAG index than those with normal creatinine clearance but there was not any significant increase of NAG activity after first dose of MTX in the patients with decreased creatinine clearance. Continued treatment with MTX resulted in a decrease in NAG activity accompanied by serum C-reactive protein concentration. CONCLUSION: The use of low dose MTX with or without NSAIDs does not influence the renal tubular function in patients with RA.

Nowak B, Jeka S, Wiland P, Szechiński J. · No affiliation provided · Joint Bone Spine. · Pubmed #19196533 No free full text.

This publication has no abstract.