Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1535101 | Meta-analysis of second-line antirheumatic drugs: sample size bias and uncertain benefit. | 1992 Jun | Placebo controlled trials of methotrexate, auranofin, penicillamine, azathioprine, sulphasalazine, gold sodium thiomalate and chloroquines were subjected to meta-analysis. The difference between drugs and placebo in the erythrocyte sedimentation rate was 8.8 mm/hr [95% confidence interval (CI), 6.4-11.3]. In multiple linear regression analyses, with the physician's global evaluation and relative change in joint tenderness count as outcome variables, a substantial sample size bias was demonstrated. The effect decreased with increasing sample size. The risk of dropping out from any cause was larger on drug than on placebo (odds ratio, 1.17; CI, 0.99-1.38). No evidence of a worthwhile effect on radiological changes was found. Of the 3439 patients, 4 went into complete remission on drug. We conclude that the benefit of second-line drugs is uncertain. | |
| 8031999 | Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes | 1994 Mar | Activated synoviocytes are major effector cells in the pathogenesis of rheumatoid arthritis (RA) because of their capacity to secrete a variety of inflammatory mediators. Among these mediators, the chemotactic proteins monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) are likely to contribute to the recruitment of inflammatory cells into the arthritic joint. We examined the effects of anti-rheumatic drugs on the MCP-1 and IL-8 production by cultured RA synoviocytes exposed to pro-inflammatory agonists. Both chemotactic cytokines were quantified by specific enzyme-linked immunosorbent assays (ELISA), and found to accumulate in the culture supernatants. Although the time course of formation was similar, the yield of IL-8 was three to 10-fold higher than that of MCP-1. Non-steroidal anti-inflammatory drugs inhibited the synthesis of prostaglandins, but did not influence the production and release of both chemotactic cytokines. Of three disease-modifying drugs tested, dexamethasone and gold sodium thiomalate (GST) inhibited the production of IL-8 and MCP-1, while methotrexate (MTX) was inactive. Dexamethasone reduced the production of MCP-1 and IL-8 by 20-65% and 60-80%, respectively, whilst GST inhibited MCP-1 and IL-8 synthesis in suboptimally, but not in optimally stimulated synoviocytes. Taken together, these results show that the production of MCP-1 and IL-8 is similarly affected by anti-rheumatic drugs and that dexamethasone is the most potent inhibitor suggesting that part of the anti-rheumatic action of glucocorticoids is due to prevention of accumulation of chemotactic cytokines acting on neutrophils and monocytes. | |
| 8523359 | Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthrit | 1995 Sep | We report the fatal disease course of 2 aged patients with rheumatoid arthritis (RA). Both had respiratory complaints after 10-15 weeks of treatment with methotrexate (MTX). After withdrawal of MTX, and despite the use of corticosteroids and ventilatory support, both died of respiratory failure. Post mortem examination showed extensive pulmonary fibrosis, bronchiolitis obliterans, and hyperplasia of type II pneumocytes. To our knowledge, this is the first report of fatal pulmonary fibrosis following short courses of low dose MTX therapy for RA. | |
| 1411190 | [3 cases of polyarthritis treated with recombinant alfa interferon]. | 1992 May | Bilateral symmetrical polyarthritis occurred in three patients (2 males and 1 female), with no previous history of inflammatory rheumatologic disease, given alpha-interferon for 1 1/2, 7, and 10 months as treatment of chronic non A-non B hepatitis, myelofibrosis, and thrombocytopenia with myeloproliferative disorder, respectively. Joint manifestations developed 1 1/2, 3, and 10 months after initiation of alpha-interferon in a dosage of 3.10(6) U three times a week, 4.5.10(6) U per day, and 8.10(6) U three times a week. Polyarthritis persisted following withdrawal of alpha-interferon in the two last patients of whom one had rheumatoid nodules and positive rheumatoid serology and the other had scleritis, exanthema, and negative rheumatoid serology. Erosive rheumatoid arthritis was diagnosed after 28 months and 12 months, respectively, in two patients who required systemic corticosteroids with antimalarials (1 case) or azathioprine after failure of methotrexate (one case). Follow-up in the third case (12 months) is too short to allow differentiation of systemic lupus erythematosus (ANA: 1/1500 H with anti-DNA antibodies 58 U/ml) and chronic autoimmune hepatitis. Reports of chronic inflammatory rheumatologic disease during alpha interferon therapy are exceedingly few in number. In the cases reported herein, alpha-interferon may have either triggered or revealed the joint disease. To prevent occurrence of this complication, exclusion from alpha-interferon therapy of patients with autoantibodies or a positive history for clinical evidence of immune dysfunction may be considered. | |
| 7482069 | [Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for malign | 1995 Aug | Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With the increased use of MTX, reports of opportunistic infections associated with MTX therapy have appeared. Fourteen cases of pneumocystis carinii (PC) pneumonia in patients receiving low dose MTX have been previously reported. Yet, no case of PC pneumonia associated with low dose MTX has so far been reported in Japan. We report the first case in Japan of PC pneumonia occurring in a patient with rheumatoid vasculitis who was receiving low dose MTX. A 70-year old woman with 13 year history of RA presented with 3-day history of rapidly aggravating dyspnea, dry cough and fever. She had been receiving MTX 7.5 mg/week for 2.5 months because of her vasculitis symptoms. She had also been receiving prednisolone 7.5 mg/day which had been successfully tapered from an initial dose of 15 mg/day. At the time of her presentation with respiratory symptoms, all of her vasculitis symptoms had been alleviated. A chest radiograph revealed diffuse interstitial shadowing bilaterally and bilateral hilar and right lower lung field infiltrates. Her arterial blood gas showed severe hypoxemia (PaO2 27.7 torr). Polymerase chain reaction assay of bronchoalveolar lavage fluid showed PC. Although the patient required ventilatory support for 9 days, she was successfully treated with trimethoprime-sulphamethoxazole and methylprednisolone pulse therapy. Eight months later, the patient was well with no evidence of vasculitis or respiratory symptoms. | |
| 8187445 | Prospidine versus methotrexate pulse in highly active rheumatoid arthritis: a controlled 6 | 1994 Mar | Twenty-seven patients with highly active, refractory rheumatoid arthritis (RA) were treated with the new anti-rheumatic drug prospidine, in view of selecting the optimum pulse regimen and comparing its short-term use with methotrexate (MTX). Prospidine was administered intravenously 500 mg every 3-5 days in the hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then orally 7.5-15 mg/week). The randomisation code was 2:1. We assessed 7 clinical and 4 lab data. The clinical improvement was noticed statistically after 2-4 weeks in 85% prospidine-patients and sustained up to 6 months in 73% (cp. 40% and 57% by the MTX). Only in the prospidine patients were a significant reduction of the mean daily prednisolone dose and the levels of rheumatoid factor and immune complexes observed. Prospidine and MTX had a similar incidence of side effects (39% and 43%), but all drop-outs in prospidine pulse were due to lack of response (26%) and to initial intolerance (4%). Drop-outs in MTX pulse were connected both with drug toxicity (14%) and with lack of response (7%). Alternate prospidine pulse, as highly anti-inflammatory, rapidly acting and well-tolerated regimen, may be used in treating severe forms of RA. | |
| 7880185 | The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, | 1995 Mar | OBJECTIVE: We created a model to estimate the total medication costs of treating patients with rheumatoid arthritis with 6 second-line agents for the first 6 months of treatment. METHODS: Drug costs were obtained from a survey of pharmacies; monitoring costs were calculated from utilization information obtained in a survey of rheumatologists; toxicity costs were obtained using decision trees to represent the evaluation and treatment of potential toxicities. Monitoring and toxicity costs were estimated using costs from the Boston University Medical Center or, for hospitalizations, using appropriate diagnosis-related group categories. The sum of the 3 components determined the total medication costs. RESULTS: The least expensive medication was penicillamine, at $10.62/week, and the most expensive was injectable gold, at $30.89/week. In terms of monitoring costs, methotrexate had the highest costs associated with necessary laboratory tests and office visits. Hydroxychloroquine had the lowest monitoring costs for office visits, and oral gold had the lowest for laboratory costs. Hematologic toxicities were the largest component of toxicity costs for all 6 medications, and renal toxicities were costly for patients taking oral gold, penicillamine, and injectable gold. Total medication costs revealed oral gold as the least expensive medication and injectable gold as the most expensive. The combination of monitoring and toxicity costs accounted for more than 60% of the total costs for all medications except injectable gold. In all cases, the cost of treating toxicities was the smallest of the 3 components. CONCLUSION: When calculating the costs of drug therapy, it is important to consider not only the price of the drug, but also the costs of monitoring and treating the toxicities that might occur. Failure to do so will result in underestimating the true costs of treatment with these medications. | |
| 1629823 | High dose intravenous methotrexate for refractory rheumatoid arthritis. | 1992 Feb | Eight patients with active rheumatoid arthritis were given high dose intravenous methotrexate (MTX) (500 mg/m2) followed by oral leucovorin every 2 weeks for up to 6 months. All patients enrolled had previously failed conventional MTX therapy. Five patients completed 6 months of therapy. Three withdrew early, one due to inefficacy, one due to gastrointestinal intolerance and one due to sciatica requiring hospital admission. Fifty percent or greater improvements were seen in 5 of 8 clinical variables in those patients who completed 6 months of therapy. Six of 8 improvements achieved statistical significance at 24 weeks. Upon discontinuing therapy, patients flared within 8 to 12 weeks. Those who were maintained by low dose MTX after the high dose protocol were able to sustain their improvement throughout the subsequent 6 months of followup. | |
| 8059130 | [Treatment of refractory rheumatoid arthritis with cyclosporine]. | 1994 Mar | The efficacy of low-dose cyclosporin-A (CyA) has been clearly demonstrated for rheumatoid arthritis. However, the long-term benefit-risk ratio remains to be investigated in patients with refractory RA. Thirty one patients were included in a prospective open study (24 females, seven males, mean age = 55 years). The mean duration of RA was 11 years and refractory RA was defined by the need of corticosteroid treatment in 26 patients and the previous failure of at least five second line drugs including methotrexate in 27 patients. Initial dosage of CyA was 3 mg/kg/d and could be progressively increased up to 5 mg/kg/d. The mean duration of the study was one year (3-39 months). At 3 months, clinically relevant improvement occurred in 22 patients (71%). Seven were withdrawn due to inefficacy. The main side-effects were hypertension (22 cases) and nephrotoxicity (18 cases) requiring the withdrawal from the study, respectively in one case and in four cases. Raised serum creatinine level had required reduction of the dosage with loss of efficacy in four cases. CyA appears to be an effective therapy for severe treatment refractory RA. Despite a high incidence of side-effects, the efficacy and the monthly management of the patients lead to a good benefit/risk ratio with a percentage of continuation of treatment of 42% at one year. | |
| 8452577 | Determinants of serious liver disease among patients receiving low-dose methotrexate for r | 1993 Mar | OBJECTIVE: To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX). METHODS: We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease. RESULTS: Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease. CONCLUSION: Serious liver disease is an uncommon, age- and dose-related complication of low-dose MTX therapy for RA. | |
| 8992004 | A modified version of Larsen's scoring method to assess radiologic changes in rheumatoid a | 1995 Oct | We describe the development and application of a modified version of the radiologic scoring method proposed by Larsen in patients with rheumatoid arthritis (RA). We modified Larsen's method adding a semiquantitative description of the loss of joint surface area and provide standardized reference films for all stages at different anatomical sites (metacarpophalangeal joints, proximal interphalangeal joints, wrists, metatarsophalangeal joints). To evaluate the method, standard anteroposterior radiographs of hands, wrists and forefeet of 24 patients with early erosive RA taken at baseline (t0) and after 36 months (t1) were read by 2 raters in a blinded fashion. The interrater difference was compared with the interpatient (t0 to t1) difference using a hierarchical analysis of variance. Moreover, the method was applied to patients included in a 2 year clinical trial to evaluate the efficacy of intramuscular methotrexate (MTX) and gold sodium thiomalate (GSTM) with radiographs taken at baseline and after 6, 12, and 24 months. There was a good agreement between the 2 raters and the change could be well documented. The estimation of the intrapatient variance (at t0 and t1) was 8 times higher than the estimation of the interreader variance. The method was easily applicable in 57 patients treated with MTX and 53 patients under treatment with GSTM, showing a slowing of radiologic progression after Month 6 with both drugs. The modification of Larsen's scoring method is a reliable measure to assess baseline status and radiologic progression in patients with RA. | |
| 8882301 | Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. | 1996 Mar | Low-dose pulse methotrexate has emerged as one of the most frequently used slow-acting, symptom-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA) because of its favourable risk-benefit profile. Methotrexate is a weak bicarboxylic acid structurally related to folic acid. The most widely used methods for the analysis of methotrexate are immunoassays, particularly fluorescence polarisation immunoassay. After oral administration, the drug is rapidly but incompletely absorbed. Since food does not significantly affect the bioavailability of oral methotrexate in adult patients, the drug may be taken regardless of meals. There is a marked interindividual variability in the extent of absorption of oral methotrexate. Conversely, the intraindividual variability is moderate even over a long time period. Intramuscular and subcutaneous injections of methotrexate result in comparable pharmacokinetics, suggesting that these routes of administration are interchangeable. A mean protein binding to serum albumin of 42 to 57% is usually reported. Again, the unbound fraction exhibits a large interindividual variability. The steady-state volume of distribution is approximately 1 L/kg. Methotrexate distributes to extravascular compartments, including synovial fluid, and to different tissues, especially kidney, liver and joint tissues. Finally, the drug is transported into cells, mainly by a carrier-mediated active transport process. Methotrexate is partly oxidised by hepatic aldehyde oxidase to 7-hydroxymethotrexate. This main, circulating metabolite is over 90% bound to serum albumin. Both methotrexate and 7-hydroxy-methotrexate may be converted to polyglutamyl derivatives which are selectively retained in cells. Methotrexate is mainly excreted by the kidney as intact drug regardless of the route of administration. The drug is filtered by the glomeruli, and then undergoes both secretion and reabsorption processes within the tubule. These processes are differentially saturable, resulting in possible nonlinear elimination pharmacokinetics. The usually reported mean values for the elimination half-life and the total body clearance of methotrexate are 5 to 8 hours and 4.8 to 7.8 L/h, respectively. A positive correlation between methotrexate clearance and creatinine clearance has been found by some authors. Finally, the pharmacokinetics of low-dose methotrexate appears to be highly variable and largely unpredictable even in patients with normal renal and hepatic function. Furthermore, studies in patients with juvenile rheumatoid arthritis provide evidence of age-dependent pharmacokinetics of the drug. These features must be considered when judging the individual clinical response to methotrexate therapy. Various drugs currently used in RA may interact with methotrexate. Aspirin might affect methotrexate disposition to a greater extent than other nonsteroidal anti-inflammatory drugs without causing greater toxicity. Corticosteroids do not interfere with the pharmacokinetics of methotrexate, whereas chloroquine may reduce the gastrointestinal absorption of the drug. Folates, especially folic acid, have been shown to reduce the adverse effects of methotrexate without compromising its efficacy in RA. Finally, both trimethoprim-sulfamethoxazole (cotrimoxazole) and probenecid lead to increased toxicity of methotrexate, and hence should be avoided in patients receiving these drugs. A relationship between oral dosage and efficacy has been found in the range 5 to 20mg methotrexate weekly. The plateau of efficacy is attained at approximately 10 mg/m2/week in most patients. No clear relationship between pharmacokinetic parameters and clinical response has been demonstrated. Overall, the dosage must be individualised because of interindividual variability in the dose-response curve. This variability is probably related, at least in part, to the wide interindividual variability in the disposition of the drug. | |
| 1536666 | Comparison of auranofin, methotrexate, and the combination of both in the treatment of rhe | 1992 Mar | OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study. | |
| 8129787 | Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. | 1994 Mar | Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information. | |
| 8675829 | Pustular psoriasis induced by hydroxychloroquine: a case report and review of the literatu | 1996 May | A variety of pharmacologic agents have been known to induce pustular psoriasis. We describe a patient with a positive personal and family history of psoriasis who developed an extensive annular pustular eruption 3 weeks after starting hydroxychloroquine (Plaquenil) for arthritis. The drug was discontinued, and she received 3 weeks of systemic and topical corticosteroids; in spite of the therapeutic intervention, showers of new lesions appeared daily, and progressed to involve 75% of the body. The development of new lesions stopped, and the older lesions began to clear after one dose of 7.5 mg of methotrexate. Subsequently, methotrexate therapy was stopped because of mild transaminase elevation; the pustular lesions then flared. New lesions stopped appearing after four doses of weekly methotrexate. The patient remains clear of lesions 6 months later. | |
| 7966062 | Underrecognized postdosing reactions to methotrexate in patients with rheumatoid arthritis | 1994 Jul | OBJECTIVE: To report previously underrecognized postdosing side effects of methotrexate (MTX). METHODS: Over a one and a half year period, in 2 practices, all patients with rheumatoid arthritis (RA) receiving weekly MTX, and volunteering symptoms within a few hours of MTX dosing were carefully questioned concerning the nature of the postdosing reaction. RESULTS: Of 356 patients, 36 (10%) reported a previously underemphasized postdosing reaction consisting of arthralgias/myalgias, fatigue/malaise or both. Sixteen patients discontinued MTX primarily because of this side effect. CONCLUSION: In these patient populations, postdosing reactions were the 2nd most common side effect (after gastrointestinal) leading to MTX withdrawal. | |
| 1599808 | Current issues of methotrexate and cyclosporine. | 1992 Jun | Methotrexate given in weekly oral-pulse regimens is rapidly becoming the most popular of the antirheumatic drugs. It seems to act relatively quickly (within 6 to 8 weeks) and patients continue to take it for a longer period of time than other antirheumatic drugs. This issue of long-term hepatotoxicity still has not been clarified, and concerns are now being raised regarding increased infection rates and whether methotrexate should be stopped before joint replacement surgery. Methotrexate, however, remains a very easy drug to use, although in the future it will probably be used as part of combination therapy. Although several clinical trials have demonstrated efficacy for cyclosporine in active rheumatoid arthritis, problems with renal toxicity are still significant. The majority of patients exhibit a rise in the serum creatinine level, although this returns to a normal level when cyclosporine is ceased. In view of this, cyclosporine is likely to remain a drug used in selected, severe cases not responding to other agents. | |
| 8714797 | Combination therapy with cyclosporin in rheumatoid arthritis. | 1995 | During the last few years, there have been rapid developments in the drug treatment of rheumatoid arthritis. This has led to research into the role of combination therapy. While past combinations of slow-acting antirheumatic drugs have resulted in either an excessive number of adverse events or a lack of increased efficacy over single agent therapy, newer combinations appear to be more promising. It has recently been demonstrated that the combination of cyclosporin and methotrexate is more effective than methotrexate alone, with no increase in adverse effects. Improved trial methodology and a better understanding of the mechanism of action of these newer agents are assisting in the development of new combinations. | |
| 8104358 | [Gold salt-induced pneumonia and CD4 alveolitis]. | 1993 | In a 62-year old man who consulted for dyspnoea, clinical, radiological and functional examinations led to the diagnosis of immunoallergic lung disease caused by gold salt therapy. Regression of the symptoms when gold salt therapy was withdrawn supported this diagnosis. Contrary to previously published cases concerning treatment with gold salts, the study of bronchoalveolar lavage (BAL) fluid yielded a lymphocytic alveolitis with a very high CD4/CD8 ratio, as already reported with methotrexate, cyclothiazide and nitrofurantoin. This case can be added to the list of drugs that may induce CD4 alveolitis; it also reminds the existence of gold salt pneumonia and permits to discuss the value of a lymphocyte subpopulation study in the BAL fluid in patients with drug-induced immunoallergic lung diseases. | |
| 8023589 | Immunological studies in patients with rheumatoid arthritis treated with methotrexate or c | 1994 Mar | One-hundred-and-two-patients (pts) with rheumatoid arthritis (RA) were observed for 12 months. Forty-eight pts were treated with a weekly low-dose of methotrexate (MTX), 23 pts with cyclophosphamide (CTX) (eight pts with one single intravenous dose, and 15 pts orally with a single daily dose), and 31 pts with nonsteroidal antiinflammatory drugs (NSAID) only. In all individuals acute phase response, i.e., C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) serum levels, and AGP microheterogeneity using affinoimmunoelectrophoresis with concanavalin A were evaluated. The phenotype of lymphocytes isolated from peripheral blood was characterized using immunofluorescence technique. Following treatment the increased level of CRP significantly decreased whereas AGP serum level remained unchanged. Among the patients, microheterogeneity of AGP expressed as reactivity coefficient (RC) was lower before treatment when compared with 17 controls (0.95 +/- 0.23 vs. 1.35 +/- 0.15, p < 0.01). After 12 months of MTX therapy AGP-RC rose significantly (1.19 +/- 0.13, p < 0.01). No changes were observed in AGP-RC levels in CTX and NSAID treated individuals. No significant differences were observed in the percentage of CD3+, CD4+, and CD8+ cells in all the patient groups, except in CTX intravenously treated patients. In this group of patients a decrease of CD4+ cells was noticed (60.1 +/- 11.5% and 43.8 +/- 12.5% before and after treatment respectively -p < 0.01). The percentage of CD19 positive cells decreased significantly during 12 months of treatment with MTX and CTX. The percentage of activated T cells (CD25+ cells and HLA-DR+ cells) remained unchanged in MTX treated patients and was reduced in both CTX groups.(ABSTRACT TRUNCATED AT 250 WORDS) |