[Clinical experience with infliximab administration in patients with rheumatoid arthritis (according to Russian register data)].

AIM: To analyse the data on infliximab administration (efficacy, tolerance, toxicity) in patients with rheumatoid arthritis (RA) in Russia by clinical evidence provided by the multicenter observation trial. MATERIAL AND METHODS: The register included 297 patients with a documented diagnosis of RA who had for the first time treated with infliximab. The efficacy of the drug was evaluated by EULAR criteria based on the dynamics of DAS28 index. RESULTS: The results of infliximab treatment show good response of RA patients to standard courses of infliximab. A good/satisfactory effect by EULAR criteria was achieved in 80% patients to week 22 of therapy and in 85% to week 46. After 6-month (22 week) infliximab treatment a good effect was achieved in 15.7% patients, satisfactory--in 64.7%; 19.6% patients did not respond. Remission (DAS28 < 2.6 units) was achieved in 7% patients. Infliximab tolerance was satisfactory. Non-severe infusion reactions were most frequent unwanted effects. To treatment week 22, ten patients developed serious side effects causing the drug discontinuation. CONCLUSION: The results of the Russian register confirm a high therapeutic potential and satisfactory tolerance of infliximab observed in real rheumatological practice of the treatment of severe RA. These results agree with those of European registers of infliximab.

[State-of-the-art biological therapy of rheumatoid arthritis].

State-of-the-art state of biological therapy of rheumatoid arthritis is analyzed. Its pathogenetic reasons are represented. Main direction of this therapy, such as blocking of tumor necrosis factor alpha and interleukin-1, inhibition of interaction between T-lymphocytes and antigen representing cells, elimination of B-cells, are considered. Special attention is devoted to new perspective methods of biological treatment, among which the special interest has first applied in RAMS Institute of Rheumatology method of interferon-gamma neutralization. Combination of anti-inflammatory, immune depressive and significant destructive actions leads to significant curative effect of biological therapy, exceeding results of the use of classic basic drugs including methotrexate. The achievement of clinical remission of rheumatoid arthritis first became the real aim of its treatment, and methods of biological therapy in contrast to former "disease-modifying" remedies could be considered as real "disease-controlling" drugs. Biological therapy revolutionized modern rheumatology and in the nearest years would demonstrated new fundamental accesses.

[Neutralisation of interferon gamma--a new trend in therapy of rheumatoid arthritis].

AIM: To evaluate objectively therapeutic potentialities of a novel method of biological therapy--blocking interferon gamma (IF-gamma)--by means of a comparative analysis of using antibodies to IF-g (anti-IF-gamma) and tumor necrosis factor alpha (anti-TNF-alpha) in resistant rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-gamma (n = 20), anti-TNF-alpha (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. RESULTS: 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3--on anti-TNF-alpha, 11--on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-gamma (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-gamma. Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. CONCLUSION: Therapeutic efficacy of anti-IF-gamma was comparable with efficacy of anti- TNF-alpha and even was superior in some aspects. The block of IF-gamma holds much promise in the treatment of RA.

[Administration of monoclonal antibodies to B-lymphocytes (rituximab) in rheumatoid arthritis in Russia].

AIM: To assess efficacy and tolerance to anti-B-cell drug rituximab in therapy of rheumatoid arthritis (RA) by the data of RF register of this drug. MATERIAL AND METHODS: Rituximab was studied in 42 patients with high RA activity. 37 patients received rituximab according to a conventional scheme: 2 intravenous 1000 mg infusions with a 2-week interval. The rest patients received 2 intravenous 500 mg infusions. The response was evaluated by DAS28 index. RESULTS: Rituximab administration resulted in almost complete elimination of B-cells from peripheral blood. This produced a significant positive effect manifesting with reduction in the number of inflamed and painful joints. This trend was evident to observation week 8 reaching maximum to week 24. Clinical response correlated with decline of inflammation as shown by ESR and CRP. According to DAS28 index, good and satisfactory results were registered in 8 weeks in 62% patients, in 16 weeks--in 86%, in 24 weeks--in 100%. Rituximab tolerance was good. CONCLUSION: Effective treatment with rituximab for rheumatoid arthritis opened a new perspective in antirheumatic biological therapy and demonstrated an important role of B-cells in the disease development. This drug is recommended for wide use in the treatment of severe rheumatoid arthritis resistant to prior therapy including TNF-alpha blockers.

[Institute of Rheumatology and progress of antirheumatic therapy]. / Institut Revmatizma RAMN i progress antirevmaticheskoi terapii.

The paper deals with the achievements of the Institute of Rheumatology in antirheumatic therapy, among them there are methods of objective assessment of antirheumatic drugs, the first use of antimalarials in the treatment of chronic rheumatic fever, discovery of immunodepressive properties of these drugs, specification of the mechanism of action of several NSAIDs. Antilymphocytic globulin, salazopyridazine and the alkylating drug dopan were used for the first time in therapy of rheumatic diseases. Administration of the most potent NSAIDs diclofenac or indomethacin to patients with acute rheumatic fever proved to be as effective as prednizolone. Special attention is paid to the combination treatment of rheumatoid arthritis with NSAIDs. The concurrent administration of aurannofin and methotrexate was shown to cause a more rapid development of clinical improvement than monotherapy with either drug. A combination of gold aurothiomalate and hydroxychloroquine and that of low doses of D-penicillamine and cyclophosphamide had no advantages over monotherapy. Revealing the therapeutical potential of antibodies to interferon-gamma in the treatment of rheumatic arthritis and psoriatic arthritis was the most important achievement of recent years. These studies open new vistas for anticytokine treatment of rheumatic diseases.

[Use of glucose-6-phosphate dehydrogenase and transketolase for characterization of pathologic processes in the myocardium in rheumatism]. / Ispol'zovanie gliukozo-6-fosfatdegidrogenazy i transketolazy dlia kharakteristiki patologicheskikh protsessov v serdechnoi myshtse pri revmatizme

In patients with active rheumatism the activity of the key enzymes of the pentose cycle -- glucoso-6-phosphatedehydrogenase and transketolase -- increases in the erythrocytes of the peripheral blood parallel with the severity of the inflammatory lesion of the heart. In patients with distrophic changes in the myocardium without concomitant carditis the level of glucoso-6-phosphatedehydrogenase did not change significantly, while the content of transketolase decreased considerably. Antirheumatic therapy helping to reduce the inflammatory reactions in the heart results in a reduction of the level of pentose cycle enzymes. The study of the ratio between glucoso-6-phosphatedehydrogenase and transketolase may prove valuable for an approximate evaluation of the predominance of inflammatory or dystrophic processes in the cardiac muscle.

[New approaches to local antirheumatic therapy]. / Novye podkhody k mestnoi antirevmaticheskoi terapii.

Local antirheumatic therapy is viewed as an important component in the total system of the treatment of rheumatic diseases. Drug-induced synovectomy, local anti-inflammatory, antifibrotic and potential immunosuppressive therapy are analyzed. Special attention is paid to local therapy based on the use of dimethyl sulfoxide. The effects of local and general treatment are realized at least partially by means of the same mechanisms. There is possibility to improve the results of general therapy at the expense of goal-oriented local treatment without producing any influence on its tolerance. In fact, every patient with rheumatoid arthritis or other articular disease should be regarded as a potential candidate for local anti-inflammatory therapy.

[New basic preparations with prolonged action in the treatment of rheumatoid arthritis]. / Novye dlitel'no deistvuiushchie (bazisnye) preparaty v terapii revmatoidnogo artrita.

A long-term comparative study of the classic basic drug-d-Penicillamin and 2 new sulfa drugs: sulfasalazin and salazopyridazin used for the first time in rheumatology, was conducted. Both drugs were shown to produce a "basic" effect in rheumatoid arthritis and to exceed d-Penicillamin in their therapeutic action. Better results were obtained with salazopyridazin. The tolerance to the new antirheumatic sulfa drugs was quite satisfactory; no severe side-effects were noted. Both drugs extend the potentialities of antirheumatoid therapy of prolonged action and warrant further use and study.

[A new non-steroidal anti-inflammatory drug pirprofen (rengasil) in the treatment of rheumatoid arthritis and osteoarthrosis]. / Novyi nesteroidnyi protivovospalitel'nyi preparat pirprofen (rengazil) v terapii revmatoidnogo artrita i osteoartroza.

The results of a double blind clinical study of pirprofen, as compared to piroxicam and placebo in 197 patients with rheumatoid arthritis, as compared to piroxicam in 200 patients with gonarthrosis and/or coxarthrosis, and as compared to naproxen in 165 patients with lumbar spondylosis, are reviewed. In rheumatoid arthritis, pirprofen (1200 mg daily) was significantly superior to placebo, and proved in some respects more active than piroxicam where its daily dose was 20 mg. In patients with osteo-arthrosis affecting major joints and the spine, pirprofen (800 mg daily) showed the same therapeutic effects as piroxicam (20 mg) and naproxen (1000 mg). Owing to its obvious anti-inflammatory effect and good tolerance, pirprofen merits large-scale use in rheumatology.

[Comparative effectiveness of chrysanol and auranofin in rheumatoid arthritis]. / Sravnitel'naia éffektivnost' krizanola i auranofina pri revmatoidnom artrite.

A randomized study of 46 patients with classic and definite rheumatoid arthritis on chrysotherapy (25 patients--auranofin orally and 21--allochrysine intramuscularly) showed a therapeutic effect of both drugs. Allochrysine turned out more effective, it was not abandoned in any patients as a result of its inefficacy. However as compared to allochrysine auranofin was slightly better tolerated.

[A comparative evaluation of the treatment results with cyclosporin A, methotrexate and azathioprine in rheumatoid arthritis patients (a preliminary report)]. / Sravnitel'naia otsenka rezul'tatov lecheniia tsiklosporinom A, metotreksatom i azatioprinom bol'nykh revmatoidnym artritom (predvaritel'noe soobshchenie).

In a randomized trial 43 patients with RA systemic manifestations received for 6 months immunodepressants: azathioprine, methotrexate and cyclosporin A (12.15 and 16 patients, respectively). Ten more patients resistant to immunodepressants were given cyclosporin A. The drugs were found to produce a positive effect on clinical symptoms and laboratory indices of the disease. Cyclosporin A is thought a basic immunodepressant without serious hematological or infectious complications. Occasionally it can be useful in failure of other immunodepressants administered to RA patients.

[Treatment of psoriatic arthritis with gold salts (chrysotherapy)]. / Lechenie psoriaticheskogo artrita soliami zolota (khrizoterapiia).

The paper is concerned with the results of a 6- and 12-month comparative randomized study of the efficacy of chrysanol (calcium-aurothiopropanol-sulfonate) in 21 patients with verified psoriatic arthritis. Patients of the study group (11 patients) received in addition to chrysanol nonsteroid antiinflammatory drugs (NAD), patients of the control group (10) received NAD only. The efficacy of annual treatment was assessed in 10 patients (5 in each group). Therapeutic efficacy was assessed on the basis of an analysis of 19 clinical and laboratory findings. Six months later improvement was noted in 80% of the patients of the study group, of them considerable improvement in 30%. A significant positive time course was observed for 9 parameters including those characterizing vertebral mobility. Improvement in the control group was noted in 50% of the patients, 2 parameters changed significantly. One year later improvement was recorded in all the patients of the study group and in 40% of the patients of the control group. A significant positive time course was noted for 10 parameters in the study group and not a single one in the control group. In the latter group 7 values got worse, the deterioration of one value was statistically significant. Side effects of chrysanol were noted in 2 patients (agranulocytosis and nephropathy). The aggravation of skin psoriasis was not noted in any patients.

[Herpes zoster--an unusual complication of gold therapy]. / Opoiasyvaiushchii lishai-neobychnoe oslozhnenie auroterapii.

The authors observed the development of herpes zoster in 2 rheumatoid arthritic patients against a background of chrysanol therapy. Such a complication should be regarded as an indication for aurum drug cancellation. The study provided an opportunity for specifying some aspects in the mechanism of action and indicated a possible immunodepressive effect.

[Piroxicam in the treatment of rheumatoid arthritis]. / Piroksikam v terapii revmatoidnogo artrita.

Open and double blind trials in 80 patients with proved and definite rheumatoid arthritis have shown that piroxicam possesses marked analgesic and antiinflammatory action, is well tolerated producing a therapeutic effect only at high doses exceeding the mean ones recommended in the literature.

[Clinico-roentgenological and scintigraphic parallels in aseptic femur head necrosis in patients with rheumatoid arthritis]. / Kliniko-rentgenologicheskie i stsintigraficheskie paralleli pri asepticheskom nekroze golovki bedrennoi kosti u bol'nykh revmatoidnym artritom.

A clinicoroentgenological study was performed in 35 rheumatoid arthritic patients (of them 24 with aseptic necrosis of the femoral heads and 11 without clinicoroentgenological signs of the hip joint involvement). Aseptic necrosis, stage II, was roentgenologically defined in 12 femoral heads, stage III in 23. An analysis of the results of the scintigraphic study showed that the RP absorption ratio in the rheumatoid arthritic patients with aseptic necrosis was significantly higher than that in the control group. Significant scintigraphic differences between stage II and III of aseptic necrosis were also revealed (the ratio of 99mTc absorption was 2.79 +/- 0.156 and 4.08 +/- 0.22, respectively).

[New approaches to biological immunomodulation therapy of rheumatoid arthritis: neutralization of basic cytokines]. / Novye podkhody k biologicheskoi immunomoduliruiushchei terapii revmatoidnogo artrita: neitralizatsiia osnovnykh tsitokinov.

AIM: Investigation of efficacy of antibodies ot interferons in rheumatoid arthritis (RA) versus relevant efficacy of the tumor necrosis factor (TNF), comparison of the above cytokines in monotherapy and combined treatment. MATERIALS AND METHODS: An open controlled randomized trial of clinical benefit and tolerance of anticytokine antibodies was performed in a group of RA patients at stage II, III and IV (1, 20 and 4 patients, respectively). The activity degree II and III was in 10 and 15 patients, respectively. All the patients had articular functional insufficiency of the second degree. 21 patients failed previous therapy with basic drugs including immunodepressants. RESULTS: The anticytokine antibodies proved to be highly effective in RA. Positive changes in teh disease activity were achieved early after the end of the 5-day course in 88% of patients. The most definite immediate therapeutic effect was noted in usage of TNF antibodies both in monotherapy and in combination with other anticytokines. Long-term effect was the best in patients given antibodies to interferon gamma. Interferon-alpha antibodies produced weaker effect. The combined treatment had no advantages over the monotherapy. CONCLUSION: A significant therapeutic effect of antibodies to interferon-gamma is indicative of an important role of this cytokine in RA pathogenesis. Anticytokine antibodies are promising as a component of combined therapy of patients with resistant RA.

[Double-blind trial of the effectiveness of antibodies to interferon-gamma and tumor necrosis factor-alpha in rheumatoid arthritis (preliminary results)]. / Dvoinoe slepoe issledovanie éffektivnosti antitel k interferonu-gamma i faktoru nekroza opukholi-alpha pri revmatoidnom artrite (promezhutochnye rezul'taty).

AIM: Objective evaluation of the effectiveness and tolerance of antibodies to interferon-gamma (TNF-gamma) vs those to tumor necrosis factor-alpha (TNF-a) and placebo in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind randomised controlled trial of effectiveness and tolerance of anticytokine antibodies was conducted in 30 patients with active RA. The drugs were given i.m. for 5 consecutive days. The results were assessed on day 7 and 28. RESULTS: Antibodies to both cytokines produced a marked therapeutic effect in RA, much greater than placebo effect. Improvement by day 7 was achieved in 9, 7 and 2 patients on anti-TNF-a, anti-INF-g and placebo, respectively. By day 28 in 8, 8 and 0 patients, respectively. Tolerance of anticytokines was good. Significant differences between the results of treatment with anti-INF-g and anti-TNF-a were not found. CONCLUSION: Administration of antibodies to INF-a proved ineffective and well tolerated method in the treatment of severe RA resistant for a number of standard basic drugs. Anti-IFN-a holds great promise when used in combination with classic antirheumatoid drugs, primarily with methotrexate.

[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.

[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.

[Effectiveness of intra-articular dimexide in combination with hydrocortisone and hydrocortisone in patients with juvenile rheumatoid arthritis]. / Effektivnos't dimeksida v sochetanii s gidrocortisone i gidro- kortizona pri vnutrisustavnom vvedenii bo'lnym iuveni'lnym revmatoidnym artritom.

A course of 4-5 intra-articular injections was given to 25 children aged 4-15 years with juvenile rheumatoid arthritis: 20% dimexide++ solution in combination with hydrocortisone (2 ml) was administered into the right knee joint and hydrocortisone (12.5 mg) into the left knee joint once a week. Dimexide++ solution combination with hydrocortisone proved to be most effective: all signs of inflammation subsided, the joint function was restored and there were no untoward reactions.