[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.

[Clinico-morphological comparisons in variants of rheumatoid arthritis (based on the data of puncture biopsy of synovial membrane)]. / Kliniko-morfologicheskie sopostavleniia pri razlichnykh variantakh revmatoidnogo artrita (po dannym punktsionnykh biopsii sinovial'noi obolochki).

Altogether 564 successive puncture biopsies withdrawn from patients with different versions of RA were subjected to morphological study with the aid of a statistical analysis of the intensity of 25 signs of synovitis evaluated according to the 5-score system. The differences in the structure of synovitis were recognized: predominance of the signs of the humoral immunity (particularly plasma cell infiltration) in patients with a mild (with a favourable evolution) version of RA and predominance of the signs of the cell-mediated immunity (macrophagal and T-lymphocyte infiltration, cytolysis, proliferation and mesenchymal transformation of fibroblasts) in a grave (incurable, invalidism-producing) version. The disease of medium gravity (running a progressive course but relatively eliminated by therapy) was characterized by the combination of and undulatory time course of the signs indicated. The greatest involution of the majority of the synovitis signs as influenced by the treatment was observed in a mild, whereas the least in the grave version of RA. It is suggested that local antibody genesis may play a protective role in RA.

[The potentials of colchicine in the combined therapy of secondary amyloidosis in patients with rheumatoid arthritis]. / Vozmozhnosti kolkhitsina v kompleksnoi terapii vtorichnogo amiloidoza u bol'nykh revmatoidnym artritom.

The authors relate the results of prolonged treatment (up to 3.5 years) with colchicin of 22 patients suffering from rheumatoid arthritis (RA) complicated by morphologically verified secondary amyloidosis of the kidneys and/or of the gingival, rectal and hepatic mucosae. Colchicin prescribed as the only slowly acting agent turned out effective in 5 out of 11 patients and in all the 11 patients given the drug in combination with basic therapy by cytostatics or, rarely, by gold drugs and D-penicillamine. The treatment efficacy could be observed both in respect to the manifestations of rheumatoid disease proper and in respect to the manifestations of amyloidosis. The drug did not produce any side effects and could be administered for a long time. In the overwhelming majority of cases, the withdrawal of colchicin, even in basic therapy continuation caused the enhancement of the manifestations of RA and amyloid nephropathy.

[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.

[Heart defects in rheumatoid arthritis patients (the results of a multiyear prospective clinico-echocardiographic study)]. / Poroki serdtsa u bol'nykh revmatoidnym artritom (rezul'taty mnogoletnego prospektivnogo kliniko-ékhokardiograficheskogo issledovaniia).

The analysis of life-time diagnosis of valvular heart disease in rheumatoid arthritis (RA) patients has been made basing on a long-term clinico-echocardiographic investigation. Within 18-year follow-up valvular disease was revealed in 17 out of 214 RA patients (7.9%). Only 3 patients developed the disease in childhood prior to RA diagnosis. In 8 patients the diagnosis of valvular disease was established in the presence of RA, in 6 RA patients the disease was determined during the follow-up period. Mitral stenosis, aortal stenosis, combined mitral valve incompetence, combined aortal defect, mitral defect and tricuspid incompetence, combined mitral defect and pulmonary artery valvular incompetence were detected in 2, 2, 3, 1, 1, and 1 patients, respectively. Valvular disease occurs more frequently in progredient seropositive RA uncontrollable by on-going therapy. The authors emphasize the value of a prospective clinical echocardiographic examination of RA patients in early diagnosis of valvular disease in them. Frequent valvular lesions in RA patients dictate the need of persistent antirheumatic therapy to inhibit the activity and prevent progression of the disease.

[Chlorbutin, azathioprine, D-penicillamine and levamisole (decaris) in the treatment of patients with rheumatoid arthritis. IV. Comparative evaluation of their effects on systemic (extra-articular) manifestations of the disease]. / Khlorbutin, azatioprin, D-penitsillamin i levamizol (dekaris) v lechenii bol'nykh revmatoidnym artritom. IV. Sravnitel'naia otsenka vliianiia na sistemnye (vnesustavnye) proiavleniia zabolevaniia.

The authors studied and compared the action of chlorbutin, azathioprin, of large and mean doses of D-penicillamine and levamisole with that of nonsteroidal antiinflammatory drugs (NAID) on rheumatoid arthritis systemic manifestations in 186 patients treated with these drugs for more than 3 months. It was shown that the basic drug compared very favourably with NAID. The cytostatics and levamisole were discovered to be highly efficacious. The authors believe that if the patients are afflicted with alveolitis and rheumatoid nephropathy, this should be regarded as indication for use of chlorbutin and levamisole.

[The healing of the bone erosions during therapy with gold preparations and D-penicillamine in rheumatoid arthritis patients]. / Zazhivlenie kostnykh érozii na fone terapii preparatami zolota i D-penitsillaminom u bol'nykh revmatoidnym artritom.

The paper is concerned with the data obtained during 17-year prospective follow-up of over 500 patients with rheumatoid arthritis (RA) who received individualized treatment mainly with basic drugs. Cases of repair of bone erosions in small joints of the hands and feet are described as are cases of complete or partial repair of osteolysis in 8 patients with significant RA treated for a long time with parenteral or oral gold drugs, or D-penicillamine in different daily doses.

[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.

[The potentials of a peroral gold preparation (Ridaura) in treating rheumatoid arthritis based on prospective observation data]. / Vozmozhnosti peroral'nogo preparata zolota (ridaury) v lechenii revmatoidnogo artrita po dannym prospektivnogo nabliudeniia.

Ridaura was given to 72 patients with true rheumatoid arthritis (RA) in the period of 6 mos to 2 yrs. Patients with I-II degree of activity and II-III x-ray stage of RA prevailed. Extraarticular RA manifestations were detected in 79% of the patients. The efficacy of Ridaura was assessed by its effect on the indices of activity (clinical manifestations of the articular syndrome, ESR, morphological signs of rheumatoid synovitis) and progression (the rates of erosive arthritis development in the hand and foot joints, the time course of the level of the serum rheumatoid factor and RA systemic manifestations). The drug efficacy was assessed with relation to the preceding variant of a RA course by the onset of treatment and after 3, 6, 12 and 18 mos. The results obtained indicated a high clinical efficacy of the drug and the presence of its basal activity which manifested itself in a good clinical effect by a decrease in the rates of x-ray progression, a serum RF level, the expression of morphological signs of synovitis and extraarticular RA manifestations, in particular myocarditis, diffuse interstitial pulmonary fibrosis, fever, and Aschoff's nodules. The therapeutic effect of the drug was on an increase in the period over 1 year. The highest efficacy of the drug was noted in RA with persistent activity of I-II degree or with activation up to II degree. Side-effects were revealed in 19% of the patients. Good tolerance of the drug was observed in 63% of the patients with a previous history of intolerance to parenteral gold drugs.

[Diclonate P in rheumatoid arthritis]. / Diklonat P pri revmatoidnom artrite.

Diclonate P (sodium diclofenac, Pliva, Zagreb) was used in the treatment of 74 patients with rheumatoid arthritis as the basic antirheumatic drug. Analgesic and antiinflammatory activity and good tolerance of three dosage forms (tablets, suppositories, ampoules) of diclonate P were established on a statistically significant basis. In some parameters the drug compares very favourably with its chemical analogs.

[A comparative evaluation of parenteral and oral preparations of gold and D-penicillamine in the treatment of rheumatoid nephropathy]. / Sravnitel'naia otsenka parenteral'nykh i oral'nykh preparatov zolota i D-penitsillamina v lechenii revmatoidnoi nefropatii.

Analysis is made of the results of the treatment with parenteral (crysanol and myochrysine) and oral (ridaura) gold drugs as well as with small doses of D-penicillamine (DP) of patients suffering from rheumatoid arthritis with the signs of nephropathy. The latter ones were identified, respectively, in 18 out of 80 patients who began receiving treatment, in 17 out of 72, and in 16 out of 61 patients. The clinical, laboratory, instrumental and morphological manifestations of nephropathy are described and analysis of their dynamics under the treatment impact is provided. It is noted that these types of basic therapy produce a beneficial effect on the manifestations of rheumatoid nephropathy. That referred to a greater measure to the gold drugs than to the small doses of DP. The degree of counteracting the symptoms of renal pathology agreed well with a good clinical effect in respect to the articular syndrome and inflammatory responses of blood. Among patients receiving crysanol, iatrogenic nephropathy was recorded in 8.75% of cases, among those on ridaura, in 2.8%, and those on DP, in 8.2% of cases. The authors provide evidence for the use of gold drugs and DP in patients suffering from rheumatoid nephropathy.

[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.

[Kidney involvement in patients with rheumatoid arthritis]. / Porazhenie pochek u bol'nykh revmatoidnym artritom.

Renal pathology was revealed in 284 out of 498 patients with rheumatoid arthritis (RA) subjected to the 15 years' prospective controlled follow-up and given individualized pharmacotherapy. Biopsy specimens of the kidney were examined in 90 cases. Of these, in 14 patients, they were examined repeatedly. On morphology the following alterations were detected in renal tissue: minimum morphological alterations (18 cases), glomerulonephritis (32 cases), amyloidosis (53 cases), interstitial nephritis (4 cases), and arteriosclerotic nephrosclerosis (1 case). In patients with nephropathy, no pathology nas revealed on morphology (5 cases). Chronic pyelonephritis was diagnosed in 137, nephroptosis in 47, nephrolithiasis in 17, papillary necrosis in 3, and drug nephropathy in 33 patients. Many patients had concomitant renal pathology. Repeated morphological examinations of renal tissue point to dynamic morphological alterations occurring during treatment and disease. Chlorbutin was found to exert a beneficial effect not only on the manifestations of arthritis but also on renal tissue. It could be seen in patients with a primary morphological diagnosis of mesangioproliferative nephritis and minimum morphological alterations in renal tissue. In some cases the clinical and morphological data did not agree, which provides evidence in favour of making renal biopsy in RA patients with a purpose of early diagnosis and specification of renal pathology, choice of the treatment policy.

[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.

[A trial of the use of the preparation Arthrotec for treating rheumatic diseases]. / Opyt primeneniia preparata atrotek dlia lecheniia revmaticheskikh zabolevanii.

A clinical trial of arthrotek (Searle) in 60 RA patients aged 16-77 years demonstrated its high anti-inflammatory activity in 47 of them. These patients have received a complete treatment course, 10 patients were not included in the overall estimations because of side affects (gastric pains and nausea) causing them to withdraw early in the treatment course, 3 patients were nonresponders. The responders experienced attenuation of joint pain, morning stiffness. Inflammation in some joints declined, the articular index decreased.

[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.

[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.

[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.