[An antidestructive effect of leflunomide in early rheumatoid arthritis].

AIM: To study effects of leflunomide on inflammatory and destructive processes in patients with early rheumatoid arthritis (RA). MATERIAL AND METHODS: The trial included 33 patients (27 females and 6 males) with a significant diagnosis of RA (A CR criteria) aged 19 to 60 years and duration of the disease from 6 months to 3 years (15.97 +/- 9.70 months). The activity of the inflammatory process and treatment efficacy were assessed by severity of the articular syndrome, duration of morning stiffness (DMS), pain and the disease activity (VAS), device examination, the disease activity by DAS28 indices, etc. The articular syndrome was assessed by the number of painful joints (NPJ), number of swollen joints (NSJ), etc. The functional status of the patient was evaluated by Keitel test, HAQ and hand grip. Calculations were made of erosive arthritis progression rate (EAPR) and joint fissure narrowing progression rate (FNPR). All the patients received leflunomide (100 mg/day for 3 days, then 20 mg/day). A 12-month course was finished by 14 patients, 4 patients were withdrawn because of side effects, the rest--by social causes. RESULTS: To the end of the trial leflunomide reduced NPJ by 84%, NSJ--by 95%, DMS--by 88%, articular pain by VAS--by 66%, the disease activity by VAS--by 70%. A positive trend in DAS28 criterium was observed (a significant suppression of RA activity after 1 month of therapy by 18%, after 4 months--by 39%, after 6 months--by 43%, by the end of the treatment--by 48%). For the initial 6 months EAPR was 0.50 +/- 0.67, for the following 6 months it lowered to 0.37 +/- 1.00, while FNPR decreased to 1.14 +/- 1.26 vs. 1.31 +/- 2 58 for initial 6 months. A positive change of the level of type 3 matrix metalloproteinase (a 20% and 16% by month 4 and to the end of the trial, respectively) was registered. CONCLUSION: A positive effect of leflunomide on RA inflammatory activity and progression rate of joint destruction was confirmed.

[Evaluation of rheumatoid arthritis activity in clinical practice].

AIM: To develop inflammatory activity index (IAI) for assessment of rheumatoid arthritis (RA) activity in wide clinical practice. MATERIAL AND METHODS: Leflunomide was given to 414 patients for 18.4 +/- 5.7 weeks, on the average. The assessment of the drug efficacy was made by arthralgia severity according to visual analog scale (VAS), duration of morning stiffness, the number of painful joints at palpation, number of swollen joints (NSJ), general condition (GC) of the patient, ESR. DAS28 was used as a basic indicator of the disease activity and efficacy. IAI was formed on the basis of DAS28 and 3 baseline components--NSJ (28 joints), GC and ESR. RESULTS: DAS28 and IAI significantly correlated (r = 0.87, p < 0.01). Comparison of pairs of these indices can specify ranges of IAI corresponding to high, moderate and low RA activity in assessment by DAS28. CONCLUSION: IAI is a simple and reliable index of RA activity in clinical practice.

[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.

[Dynamic changes in synovitis activity after intra-articular administration of xefocam in patients with rheumatoid arthritis (according to clinical and device examinations)]. / Dinamika aktivnosti sinovita posle vnutrisustavnogo vvedeniia ksefokama bol'nym revmatoidnym artritom (dannye klinicheskogo i instrumental'nykh metodov issledovaniia).

AIM: To assess efficacy of intraarticular administration of lornoxicam (xefocam) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Xefocam was injected into the knee joints of 58 patients with RA once a week for 3 weeks in a dose 8 mg. The treatment efficacy was evaluated by changes in the severity of arthralgias, pain in the joints at palpation, circumference of the knee joints at the level of the upper edge of the patella, ultrasound and thermography of the knee joints. RESULTS: Xefocam relieved arthralgia (in 44 patients at least by 30%), pain in the joints at palpation and joint circumference. Ultrasound investigation registered a significant thinning of the synovial membrane and amount of exudates. CONCLUSION: If local steroid therapy is not definitely indicated, intraarticular administration of xefocam can be effectively used for suppression of moderate inflammation in the joints in RA patients.

[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.

[Combined immunomodulating therapy in rheumatoid arthritis]. / Kombinirovannaia immunomoduliruiushchaia terapiia revmatoidnogo artrita.

Monotherapy with methotrexate (MT) was compared to combined therapy MT+tactivin (T) in a 2-year clinical trial including 127 patients with rheumatoid arthritis (RA). MT was given to 88 patients in a weekly dose 7.5 mg. In 39 patients this dose was given in combination with subcutaneous injections of T (100 micrograms two times a week for a months, then once a week). Both treatments induced a significant decline in severity of arthralgia, in the number of joints with inflammation, in the level of C-reactive protein and in ESR. Morning stiffness and pains in the joints at palpation were achieved after MT+T combination. Side effects were similar in both treatments.

[The combined intensive therapy of rheumatoid arthritis with systemic manifestations]. / Kombinirovannaia intensivnaia terapiia revmatoidnogo artrita s sistemnymi proiavleniiami.

The efficacy of pulse therapy in combination with hemosorption or plasmapheresis, pulse therapy without extracorporeal treatment and methotrexate has been compared for 40 patients with rheumatoid arthritis (RA) with extra-articular manifestations. All kinds of intensive treatment were effective. Extracorporeal methods and pulse therapy relieved extra-articular symptoms. Isolated pulse therapy alleviated articular syndrome. The best results were obtained in double filtration of plasma in combination with pulse therapy. Such approach ensured improvement both articular and extra-articular inflammation. Combined intensive therapy proved an effective modality in RA able to produce responses in severe disease.

[A comparative evaluation of combined immunocorrective therapy in rheumatoid arthritis with systemic manifestations (joint Soviet-Polish research)]. / Sravnitel'naia otsenka kompleksnoi immunokorrigiruiushchei terapii revmatoidnogo artrita s sistemnymi proiavleniiami (sovmestnoe sovetsko-pol'skoe issledovanie).

Thirty-two patients with rheumatoid arthritis were included in the trial. Each of them was assigned to one of the 4 groups comparable by the main features. Each group entered 8 patients. Group 1 patients underwent hemosorption weekly for 3 weeks. After the second procedure cyclophosphamide was added at a single IV dose 1000 mg. After the third procedure the treatment was continued with methotrexate (7.5 mg, weekly). Group 2 began the treatment with methotrexate (7.5 mg, weekly). Group 3 received cyclophosphamide 200 mg IV twice a week 6 times and then 200 mg weekly orally till a total dose of 2 g. Group 4 received azathioprine in a daily dose 100 mg. The treatment with nonsteroidal antirheumatic drugs and corticosteroids was continued unchanged. After 6 months we did not see significant differences between the 4 groups.

[The clinico-morphological assessment of the efficacy of local radiation therapy in rheumatoid arthritis]. / Kliniko-morfologicheskaia otsenka éffektivnosti lokal'noi luchevoi terapii pri revmatoidnom artrite.

Ten patients with rheumatoid arthritis underwent arthroscopy of knee joints and spot biopsy of the synovial membrane before and 6-12 months after intraarticular injection of radioactive gold-198. In 8 joints there was a decrease of inflammatory infiltration of the synovial membrane. Still, the clinical signs of arthritis persisted in 5 of them. In 3 cases, the clinical and morphological manifestations of arthritis remained practically unchanged. The decrease of inflammatory infiltration of the synovial membrane may favour a reduction of destructive potential of chronic synovitis even if the exudative component of inflammation is preserved. The clinicomorphological estimation of the results of local radiotherapy is more informative than the purely clinical one, for it allows the positive dynamics to be recorded even in the absence of evident clinical improvement.

[Immunogenetic prognosis of the effectiveness of cytostatic therapy of rheumatoid arthritis]. / Immunogeneticheskoe prognosirovanie éffektivnosti ysitostaticheskoi terapii revmatoidnogo artrita.

The time course of in vitro cellular immune reactions by using cyclophosphane, prospidin , and methotrexate was examined in 39 patients with rheumatoid arthritis to make predictions of the efficacy of its cytostatic therapy. The agents were evaluated for effects on the expression of Ia-like antigens on the peripheral lymphocytes and synovial fluid of the patients. The optimal doses of the agents for this testing had been chosen in the lymphoid cells from MRL31 lpr mice. The active dosage forms of the cytostatics for the experiment were obtained by administering native agents into the retrobulbar plexus of Balb/c mice, followed by blood isolation of active metabolites . The Ia-like antigen pre-expression index which is the ratio of the proportion of Ia-positive lymphocytes in control cultures to that of the cells in the culture after drug addition was used as a marker of the baseline cellular immunity in the patients. The patients having the index more than 1.5 were considered to be sensitive, those with less than 1.5 were insensitive to the drug. Thus, the Ia-like antigen pre-expression index may be used as a predictor in the assessment of the expediency of prospidine use.

[Radioisotope synovectomy in multi-modality treatment of rheumatoid arthritis]. / Radioizotopnaia sinovéktomiia v kompleknom lechenii revmatoidnogo artrita.

The colloid solution of radioactive gold 198 was administered to 91 knee joints of 50 patients with rheumatoid arthritis in a dose of 5-7 mCu. The patients were examined before and 6-12 months after radionuclide synovectomy. The treatment turned out effective in 35% of the cases, while in 19% of the cases, the effect was assessed as beneficial, and in 16% as satisfactory. The treatment efficacy decreased with age and disease standing. Three groups of the joints were distinguished in relation to the absorbed dose of ionizing radiation. In group I, this parameter constituted less than 80 Gy, in group II, from 80 to 100 Gy, and in group III, over 100 Gy. The efficacy of the different absorbed doses was assessed by the double blind method. In group I, the increase of the absorbed dose to over 100 Gy maintained 25%, and in group III, in 72% of the cases. Therefore, the increase of the absorbed dose to over 100 Gy maintained a significant (p less than 0.01) rise of the treatment efficacy.