[The role of laboratory biomarkers in monitoring of rituximab biosimilar therapy (Acellbia, "BIOCAD") in patients with rheumatoid arthritis].

AIM: to evaluate the role of laboratory biomarkers in monitoring effectiveness of rituximab (RTM) biosimilar therapy in a total dose of 1200 mg. MATERIALS AND METHODS: 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54-66.5) years, mean disease duration 39.5(20-84) months, mean DAS28 5.6(4.9-6.8)) received two intravenous RTM biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX. RESULTS: RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p.

[Experience in long-term therapy of active rheumatoid arthritis with leflunomide].

AIM: To study therapeutic potential of a novel basic drug leflunomide in suppression of activity and progression of rheumatoid arthritis (RA). MATERIAL AND METHODS: Leflunomide efficacy was investigated in a 36 month trial including 50 patients with moderate and high activity RA. Monthly registrations were made of the articular syndrome quantitative parameters (Richi's index, number of painful and swollen joints, severity of pain and general condition of the patient), morning stiffness duration, ESR, CRP, RF. Leflunomide efficacy was assessed by EULAR and ACR criteria. Dynamics of the extrajoint manifestations observed in 70% patients before therapy were examined clinically and by device tests. Speed of progression of erosive arthritis was quantified by a modified Sharp's method in hand and foot joints, carpal bones each 6 months. Arava tolerance was controlled clinically and by laboratory tests. RESULTS: Leflunomide was found effective in 94% RA patients. A rapid (within the first month) and significant improvement in parameters of articular syndrome and CRP level was observed. To month 4 of therapy 1/5 patients achieved remission by EULAR criteria, to month 12--1/3 patients. By ACR criteria, 6-month leflunomide treatment produced good and exellent results in 71% patients which persisted up to the 36th month of therapy. The effect was better in shorter history of RA, moderate RA, in the absence of osteolyses and ankyloses. Leflunomide significantly reduced RF concentration in the serum, suppressed extrajoint RA manifestations (except Sjogren's syndrome). The mean number of new joint erosions for 6 consecutive months was 2.93 +/- 3.2, 1.41 +/- 1.8, 0.78 +/- 2.0 (median 0), while progression coefficient corresponded to slow progression to the treatment month 18. No new erosions occurred after 12 months of arava treatment in 41% patients and after 18 months--in 62%. CONCLUSION: Leflunomide is well tolerated. The drug was discontinued because of cutaneous pruritus and diarrhea in 5 and 1 patients, respectively.

[Combined medication ARTRA in the treatment of osteoarthrosis].

AIM: To study clinical effectiveness, safety and duration of the effect of combined medication ARTRA (500 mg glucosamine hydrochloride+500 mg chondroitine sulphate) in osteoarthrosis. MATERIAL AND METHODS: Ninety women aged 40-75 suffering from knee OA and satisfying diagnostic criteria for OA of American Rheumatological Committee having x-ray II-III stages according to Kellgren-Lawrence; with distinct pain syndrome (pain intensity at walking 40 mm and more by the analogue visual scale); taking NSAIDS regularly during 30 days within 3 months before the study were enrolled in the study. The patients were randomly divided into 2 groups: 45 patients of the study group taking 1 tablet ARTRA 2 times a day within the first month, than 1 tablet a day within the following 5 months and diclofenac sodium 50 mg 2 times a day with gradual decrease of the dosage as the pain was decreasing; 45 patients of the control group taking only diclofenac sodium 50 mg twice a day during 6 months. Clinical examination of the patients was done before the treatment, 30, 120 and 180 days after the study. Long-term effects of ARTRA was evaluated 3 months after the study. The treatment efficacy was assessed by WOMAC index, daily need in NSAIDS intake, evaluation of the efficacy by the patient and the doctor. RESULTS: The true WOMAC index decreased in 4 and 6 months of therapy in the study group (p < 0.03). 3 months after the treatment the study group patients experienced continuous reduction of the functional index and pain intensity unlike of the control patients experiencing a pain increase and worsening of joints functional ability. When analysing pain syndrome according to VAS, after 4 months of the treatment pain was relieved more in the study group (p = 0.008). The differences were stable for 6 months. On aftertreatment month 3 pain syndrome tended to attenuation in the study group but to intensification in the controls. While taking ARTRA, the patients decreased their need in NSAIDS intake (diclofenac). After 1 month of therapy 4.5% patients gave up taking diclofenac; after 4--20%, after 6--40%. Objective and subjective effects did not differ much (94 and 90%, respectively). ARTRA tolerability was very good. None of the patients of the study group discontinued therapy because of side effects, in the control group 14 patients gave up diclofenac because of the adverse effects. CONCLUSION: Combined ARTRA medication decreases pain, improves joint function. Regular intake of ARTRA helps decrease NSAIDS dosage or discontinue intake in many cases. ARTRA is very well tolerated and is safe. ARTRA has an evident long lasting effect.

[Changes in indices of inflammatory activity in patients with rheumatoid arthritis during early stages of basic therapy with leflunomide]. / Dinamika pokazatelei vospalitel'noi aktivnosti u bol'nykh revmatoidnym artritom na rannikh étapakh bazisnoi terapii leflunomidom.

AIM: To assess leflunomide efficacy and tolerance in patients with rheumatoid arthritis (RA) during the first four months of the treatment. MATERIAL AND METHODS: The study included 200 RA patients treated in four Moscow clinical centers. Leflunomide was given in a dose of 100 mg/day for 3 days, then 20 mg/day for 16 weeks. The activity of the disease according to the criterion DAS 28 was assessed before the treatment and 4, 8, 12 and 16 weeks after the treatment start. RESULTS: RA activity diminished considerably after one month of leflunomide treatment. Later, the articular syndrome continued to improve. A significant improvement by DAS 28 was observed after 16 weeks of the treatment in 65% (129 of 200) patients, high RA activity persisted only in 17 of 90 patients. CONCLUSION: Leflunomide reduces articular inflammation and raises RA patients' quality of life at early stages of the treatment. This reduction continued for 4 months of the study. Therefore, adequate assessment of leflunomide efficacy should be made only after 4-6 months of therapy.

[Use of monoclonal antibodies to tumor necrosis factor (remicade) in rheumatoid arthritis: preliminary results]. / Primenenie monoklonal'nykh antitel k faktoru nekroza opukholi (remikeid) pri revmatoidnom artrite: predvaritel'nye rezul'taty.

AIM: To study effectiveness and tolerance of monoclonal antibodies to tumor necrosis factor (the drug remicade) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Remicade treatment results are considered for 25 RA patients receiving methotrexate the activity of which was inadequate for these patients. Remicade was infused intravenously in a dose 200 mg 4 times for 22 weeks. RESULTS: Remicade produced positive clinical and laboratory effects as early as the first infusion. The response was observed during 22 weeks of the treatment in 17 of 25 patients. Remicade tolerance was good. One patient failed the treatment because of development of collapse. CONCLUSION: Pilot results of remicade trial point to its high therapeutic potential and perspectives in rheumatology.

[Soluble receptors of TNF-alpha with molecular mass 55 kDa in rheumatoid arthritis: clinical role]. / Rastvorimye retseptory FNOalfa s molekuliarnoi massoi 55 kDa pri revmatoidnom artrite: klinicheskoe znachenie.

UNLABELLED: To evaluate clinical implications of the serum level of soluable receptors of tumor necrosis factor alpha (TNFa) with molecular mass 55 kDa (rTNF-55R) in rheumatoid arthritis, serum levels of rTNF-55R and rTNF-75R were measured with the use of radioimmunoassay in 76 RA patients, 38 donors and in 25 RA patients, 10 donors, respectively. RESULTS: Elevated serum level of rTNF-55R was recorded in 55.3% RA patients. This level correlated with basic clinical and laboratory parameters of RA, the disease activity, values of DAS indices. It is concluded that a serum level of rTNF-55R adequately reflects clinico-laboratory activity of RA and its measurement can be used for assessment of RA activity and treatment efficiency.

[Nimesil effectiveness in rheumatoid arthritis]. / Effektivnost' nimesila pri revmatoidnom artrite.

Clinical efficiency and safety of nimesil were studied in the multicenter open clinical trial of 52 patients with verified rheumatoid arthritis. Nimesil was given for 12 weeks in a daily dose 200-400 mg in addition to basic therapy. Clinical and laboratory parameters were assessed after 4 and 8 weeks of the treatment and after its end. The treatment produced a significant positive response of the articular syndrome. Marked improvement was registered in 11 (23.4%) patients, improvement--in 33 (79.2%) patients. Side effects were reversible and occurred in 8 (15.3%) patients. In 5 patients the drug was withdrawn. The conclusion is made on high efficiency and good tolerance of nimesil in rheumatoid arthritis patients.

[Current approaches to assessment of rheumatoid arthritis activity]. / Sovremennye podkhody k otsenke aktivnosti revmatoidnogo artrita.

AIM: To compare domestic criteria of RA activity and the disease activity scores (DAS). MATERIAL AND METHODS: Russian criteria of RA activity and DAS were used in 99 RA patients. RESULTS: It is shown that RA activity by DAS is higher than when it is assessed by criteria practiced in Russia. CONCLUSION: Further studies are necessary to examine clinical value of DAS criteria.

[Soluble receptors of TNF-alpha in rheumatoid arthritis]. / Rastvorimye retseptory faktora nekroza opukholi pri revmatoidnom artrite.

The serum level of soluble TNF-alpha receptors with molecular mass 55 kDa (sTNF-a55R) was measured by enzyme immunoassay with commercial kits in 30 patients with rheumatoid arthritis (RA) and 38 healthy donors. High sTNF-a55R serum levels were registered in 90% of RA patients. These levels correlated with RA activity by DAS. Thus, assay for sTNF-a55R can be used for assessing RA activity.

[Subreum efficacy and tolerance in patients with early rheumatic arthritis]. / Effektivnost' i perenosimost' subreuma u bol'nykh s rannim revmatoidnym artritom.

AIM: To evaluate effectiveness and tolerance of subreum in early rheumatoid arthritis (RA). MATERIAL AND METHODS: 44 patients with early rheumatoid arthritis. Subreum was given as a single drug and in combination with other basic drugs. Tolerance was evaluated in all the examinees, the effect--in 13 patients who finished the 6-month treatment by the articular syndrome, by ACR, DAS and HAQ criteria. RESULTS: By DAS, a good response was achieved in 2 patients (15%), a satisfactory one--in 3 (23%) patients. By ACR criteria, a 20% and 50% improvement was obtained in 3 (23%) and 4 (31%) patients. Side effects were absent in 41 (93%) patients. CONCLUSION: Subreum proved effective and well tolerable in early RA.

[Soluble adhesion molecules (P-selectin, ICAM-1 and ICAM-3) in rheumatoid arthritis]. / Rastvorimye molekuly adgezii (P-selektin, ICAM-1 i ICAM-3) pri revmatoidnom artrite.

AIM: Investigation of serum levels and clinical role of soluble intercellular molecules of adhesion (pICAM-1, PICAM-3 and pP-selectin) in rheumatoid arthritis (RA). MATERIALS AND METHODS: Enzyme immunoassay with Bender MedSystem kits (Austria) was employed to measure serum concentration of soluble intercellular molecules of adhesion in 36 RA patients. RESULTS: Elevated levels of serum pICAM-1, pICAM-3 and pP-selectin were registered in 74.2, 28.6 and 25.7% of RA patients, respectively. Content of pP-selectin more strongly correlated with activity and severity indices than that of pICAM-3 (p < 0.001). Content of pICAM-1 and clinical picture of RA were unrelated. CONCLUSION: Levels of pP-selectine can characterize RA activity.

[Structum (chondroitin sulfate)--a new agent for the treatment of osteoarthrosis]. / Struktum (khondroitinsul'fat(--novoe sredstvo dlia lecheniia osteoartroza.

AIM: To study efficiency and tolerance of Structum in gonarthrosis patients as well as duration of its effect after discontinuation. MATERIALS AND METHODS: 100 patients with femorotibial gonarthrosis aged 45 years and older entered an open randomised trial. They had knee joint arthrosis satisfying diagnostic criteria OA ACR at stage II-III according to Kellgren-Lawrence with pain syndrome. Walking pain intensity was > or = 30 mm by the visual analogue scale (VAS), Leken total functional index > or = 4 and < or = 11. Antiinflammatory drugs (AI) were regularly taken for 30 days for the 3 pretreatment months. 50 patients of the study group received Structum and ibuprofen (1200 mg/day) for 6 months. 50 patients of the control group received ibuprofen only. The two groups were followed up for 3 months. Clinical examination was made monthly. RESULTS: There were significant differences between the groups by the Leken's index (p < 0.005), VAS, pain, daily AI drug requirement. Structum proved more effective. Tolerance was good. Side effects were observed only in two patients (diarrhea and nausea). In the control group, side effects made 15 patients to discontinue the treatment. CONCLUSION: Structum is a new effective drug against gonarthrosis which reduces pain, improves joint function. It is well tolerated and allows to diminish the dose of AI drugs. The response to Structum persisted for 3 months after the treatment.

[Neopterin: laboratory marker of cellular immunity activation in rheumatoid arthritis]. / Neopterin: laboratornyi marker aktivatsii kletochogo immuniteta pri revmatoidnom artrite.

AIM: Measurement of neopterin in the serum of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 59 patients with verified RA diagnosis (22 cases of joint lesion stage I-IIa, 27 of stage IIb-IIIa, 10 of stage IIIb-IV established roentgenologically, 48 patients were seropositive by IgM-rheumatoid factor) were examined for concentrations of serum neopterin and C-reactive protein (CRP). The activity and prognostic factors were characterized by modified Wilke method, the severity index was calculated. 100 healthy donors served controls. RESULTS: Immune inflammation in RA develops with growing neopterin concentration in the serum. This concentration well correlates with inflammation activity and intensification of systemic symptoms. CONCLUSION: Neopterin measurements may be important for determination of inflammation activity in RA. Further efforts should be made to ascertain relationships between neopterin hyperproduction and disturbances of cellular immunity in RA, clinical value of neopterin assays compared to the other laboratory evidence, feasibility of using neopterin levels to define prognosis and efficacy of on-going therapy.

[Comparison of myocardial effects of various antirheumatic modalities in patients with rheumatoid arthritis (prospective clinico-echocardiographic study)]. / Sravnitel'naia otsenka vliianiia razlichnykh antirevmaticheskikh sredstv na miokard u bol'nykh revmatoidnym artritom ( prospektivnoe kliniko-ékhograficheskoe issledovanie).

A prospective study was conducted of basic antirheumatic drugs (chrisanolum, myocrisin, ridaura, chlorbutin, D-penicillamine) versus nonspecific antiinflammatory treatment in 127 patients with rheumatoid arthritis (RA). The drugs were compared by their effect on myocarditis. Basic antirheumatic drugs were found much superior to nonsteroid antiinflammatory drugs. The highest response was registered for chrisanolum myocrisin and chlorbutin after 6-12 month continuous treatment. Warning: chrisanolum, myocrisin and ridaura may produce unwanted short-term effects on left ventricular contractility in developing extracardiac complications of aurotherapy.

[A multicenter evaluation of efficacy and tolerance in the local treatment with dolgit cream of patients with osteoarthrosis]. / Mnogotsentrovaia otsena éffektivnosti i perenosimosti lokal'noi terapii kremom dolgit u bol'nykh osteoartrozom.

A 2-week clinical trial of cream dolgit efficacy and tolerance in 76 patients with primary osteoarthritis in 8 rheumatological centers showed this preparation to reduce local pain syndrome in 70.1%, palpation pain sensitivity in 79.2%, joint swelling in 75.5% of patients. Unwanted reactions in the form of skin itch at the site of application were reported in 7.8% of cases.