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9610077 Methotrexate in rheumatoid arthritis: a 2 year experience at a university hospital in Paki 1998 Jan In this study we report our two years experience of methotrexate (MTX) in the management of rheumatoid arthritis (RA) at the Aga Khan University Hospital, Karachi. We studied the clinical course of 124 RA patients. The mean age was 44 +/- 11 years (range 19-72) and mean duration of RA was 5 +/- 4 years (range 0.3-25). Female to male ratio was 10:2.4 (100F:24M). All of them were diagnosed according to the criteria set by American Rheumatism Association. The mean value of ESR was 60 +/- 30 (Range 3-128). Fifty one percent had severe disease (> 10 joints involved and evidence of erosions and deformities). Twenty-one patients had extra-articular manifestations. None of them had received MTX previously. Their kidney and liver functions were assessed to be normal. Patients were divided into two groups. One group (n = 92) received MTX (7.5-10 mg/week) as initial treatment, while the other group (n = 32) was given other disease modifying anti-rheumatic drugs (penicillamine, salazopyrin, gold, or chloroquine) followed by MTX. Assessment of the treatment outcome and development of any adverse reactions was carried out at 3-month interval over an average period of 1 year. Assessment of the treatment outcome in the group which received MTX as initial drug revealed the response to be excellent in 13%, good in 70%, fair in 11% and variable in 4%. In the group which received MTX as second-line of therapy, 59% of the patients had the response from good to excellent, while 25% of the patients exhibited poor to fair response. Regarding side-effects of MTX treatment, 57% exhibited none, while 35% had nausea and vomiting. Alopecia was the next common toxicity in these patients. Two individuals had abnormal liver function tests (value twice more than normal), while one developed lung fibrosis. MTX despite its adverse effects in some of the patients is still an effective, well tolerated and inexpensive disease modifying drug in RA.
11718162 Treatment of rheumatoid arthritis: unknown long-term effects. 2001 Apr (1) Rheumatoid arthritis, a chronic disease, is defined by a set of clinical, radiological and biochemical criteria. The diagnosis is initially uncertain. (2) Many patients have functional disability 10 years after onset, while others may have little or none. (3) The symptomatic and long-term efficacy of physical (nondrug, nonsurgical) therapies is poorly documented. (4) Various surgical approaches may restore a degree of functional capacity. (5) The use of paracetamol, possibly combined with codeine, can avoid recourse to nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are the best-assessed analgesics in this setting but carry a risk of severe adverse effects. (6) All long term treatments for rheumatoid arthritis carry a risk of severe adverse effects, and their chronic effects are poorly documented. There is no firm evidence that long term treatments reduce the risk of serious disability or death. (7) Methotrexate is the best-tolerated slow-acting antirheumatic in the medium term, despite a risk of hepatic cirrhosis, pulmonary fibrosis and haematological disorders. (8) Hydroxychloroquine and sulfasalazine are less effective. Hydroxychloroquine carries a risk of retinal damage, while sulfasalazine can cause haematological disorders and skin problems. Chloroquine seems to be slightly more effective than hydroxychloroquine, but at the cost of more adverse effects. (9) The adverse effects of D-penicillamine and injectable gold salts often require treatment withdrawal. (10) The risks associated with immunosuppressants such as ciclosporin mean that these agents should not be used for first-line treatment. (11) The place of various combinations of slow-acting antirheumatics remains to be established. (12) Recourse to systemic steroids must be minimised but is sometimes unavoidable. Low doses are usually adequate. (13) Treatment risks in elderly subjects and patients with comorbidity must be taken into account. (14) Women and men of child-bearing potential who have rheumatoid arthritis must be warned about the toxicity of antirheumatic drugs for the fetus and the effects on fertility.
10573044 Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methot 1999 Nov 22 CONTEXT: Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA). OBJECTIVE: To compare the efficacy and safety of leflunomide treatment with placebo and methotrexate treatment in patients with active RA. DESIGN: Randomized, double-blind, placebo, and active-controlled 12-month study. SETTING: Forty-seven university and private rheumatology practices in the United States and Canada. PATIENTS: Diagnosis of RA by the American College of Rheumatology (ACR) criteria for duration of 6 months or longer and no previous methotrexate treatment. INTERVENTION: Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk). MAIN OUTCOME MEASURES: American College of Rheumatology success rate (completed 52 weeks of treatment and met the ACR > or = 20% response criteria), disease progression as assessed by x-ray films, and improvement in function and health-related quality of life using the intent-to-treat population. RESULTS: The 482 patients studied were predominantly women (mean age, 54 years; mean disease duration, 6.7 years) for whom a mean of 0.8 disease-modifying antirheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P<.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P=.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P<.001 and P<.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy. CONCLUSIONS: Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life.
11027115 Leflunomide for rheumatoid arthritis. 2000 Jul Disease-modifying antirheumatic drugs (DMARDs) are given to patients with rheumatoid arthritis (RA) to prevent synovitis, slow destruction of articular cartilage and bone, preserve function and control systemic manifestations of the disease. Recognition that irreversible joint damage often occurs early in RA has led to much prompter use of DMARDs, with sulfasalazine or methotrexate commonly considered the treatment of first choice. Leflunomide (Arava-Aventis) is a new DMARD, licensed for the treatment of adults with active RA. The manufacturer claims that leflunomide has "comparable efficacy to methotrexate and sulphasalazine", with a "faster onset of action", and an "acceptable tolerability profile". Here, we consider the place of leflunomide in the management of patients with RA.
11355216 What's new in rheumatoid arthritis? An evidenced based review. 2001 Apr BACKGROUND: Rheumatoid arthritis (RA) is the most common inflammatory arthritis and has been associated with significant functional impairment and a shortened life expectancy. Fortunately, over the past 10 years, there has been a significant change in its management, which has resulted in improved outcomes for RA patients. OBJECTIVE: To critically appraise the recent evidence which affects the contemporary management of RA. DISCUSSION: The bulk of recent evidence suggests that disease modifying anti-rheumatic drugs (DMARDs) should be commenced early and continued indefinitely in RA patients. Single DMARD therapy may be sufficient in some patients but combinations, particularly those which include methotrexate, improve symptomatic and radiological outcomes. The use of newer therapies, including leflunomide and tumour necrosis factor-alpha blocking drugs, promise to further improve these outcomes.
9751087 Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha 1998 Sep OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.
9710888 Soluble tumor necrosis factor receptor (p75) fusion protein (ENBREL) as a therapy for rheu 1998 Aug Soluble tumor necrosis factor (TNF) receptor fusion protein (p75) (Enbrel) is a reversible inhibitor of the biologic effects of TNF. Enbrel has been shown in placebo-controlled trials to significantly improve the signs and symptoms of rheumatoid arthritis. Clinical trials are now in progress to assess the safety and efficacy of Enbrel in combination with methotrexate in refractory rheumatoid arthritis along with trials to compare Enbrel to methotrexate in patients with early rheumatoid arthritis.
10343521 Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocyste 1999 Feb OBJECTIVE: To study the influence of sulphasalazine (SSZ), methotrexate (MTX), and the combination (COMBI) of both on plasma homocysteine and to study the relation between plasma homocysteine and their clinical effects. METHODS: 105 patients with early rheumatoid arthritis (RA) were randomised between SSZ (2-3 g/day), MTX (7.5-15 mg/week), and the COMBI (same dose range) and evaluated double blindly during 52 weeks. Plasma homocysteine, serum folate concentrations, and vitamin B12 were measured. The influence of the C677T mutation of the enzyme methyl-enetetrahydrofolatereductase (MTHFR) gene was analysed. RESULTS: A slight trend towards increased efficacy and an increased occurrence of minor gastrointestinal toxicity was present in the COMBI group, no differences existed clinically between SSZ and MTX. Only a slight and temporary increase in plasma homocysteine was found in the SSZ group, in contrast with the persistent rise in the MTX group and the even greater increase in the COMBI patients. Patients homozygous for the mutation in the MTHFR gene had significantly higher baseline homocysteine, heterozygous MTHFR genotype induced a significantly higher plasma homoeysteine at week 52 compared with no mutation. No correlation was found between clinical efficacy variables and homocysteine. Patients with gastrointestinal toxicity had a significantly greater increase in homocysteine. CONCLUSION: A persistent increase in plasma homocysteine concentrations was observed in patients treated with MTX alone and more pronounced in combination with SSZ, in contrast with SSZ alone. An increase in plasma homocysteine is related to the C677T mutation in MTHFR. A relation in the change in homocysteine concentrations with (gastrointestinal) toxicity was found, no relation with clinical efficacy existed.
10555887 Disappointing longterm results with disease modifying antirheumatic drugs. A practice base 1999 Nov OBJECTIVE: To evaluate the longterm effectiveness of disease modifying antirheumatic drugs (DMARD) in an inception cohort of patients with rheumatoid arthritis (RA) seen by rheumatologists. METHODS: We performed a retrospective audit of the records of patients with onset of RA between January 1985 and June 1994. Charts were reviewed from the time of diagnosis to the last consult. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard regression to adjust for potential confounders. RESULTS: A total of 2296 DMARD therapies were analyzed. Roughly half were started within 2 years of disease onset. By 16 months, 50% of the DMARD therapy courses had been discontinued, and after 4.5 years 75% had been discontinued. Over all, methotrexate (MTX) had the highest probability of continuation. After roughly 3 years 50% of patients were still receiving MTX, compared to one-third of patients who received antimalarials or intramuscular gold, 30% D-penicillamine, 25% sulfasalazine, and 18% oral gold. After 6 years, when considering all DMARD together, only 20% of the therapies had not been discontinued, with no substantial differences between drugs. Toxicity from gold compounds occurred within the first 18 months of therapy and stabilized thereafter. For MTX, withdrawals due to toxicity continued throughout therapy. CONCLUSION: This is the largest observational study examining the longterm termination rates of DMARD in patients followed from the time of their initial consult. Our results confirm previous reports of short therapeutic times, even for patients treated early in the course of their disease. MTX appears to be the best drug within the first 5 years of disease. These differences, however, decrease in the longer term. It is unclear whether the results observed for MTX within the first years of therapy translate to better health status in the longer term when compared to other DMARD.
10796399 Methotrexate for rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term efficacy and toxicity of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing MTX against placebo in patients with RA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the trials independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Five trials and 300 patients were included. A statistically significant benefit was observed for MTX when compared to placebo. Statistically significant differences were observed for all measures except ESR. The standardized weighted difference (effect size) between MTX and placebo for the various outcome measures varied between -0.43 and -1.5. No differences were observed in the total number of withdrawals and dropouts (OR = 0.95), although patients on MTX were three times more likely to discontinue treatment because of adverse reactions (OR=3.47) and four times less likely to withdraw due to lack of response (OR=0.22). REVIEWER'S CONCLUSIONS: Twenty-two percent of people on MTX withdrew due to adverse effects compared to seven percent of the placebo group. MTX has a substantial clinically and statistically significant benefit in the short term treatment of patients with RA.
9569999 The effects of non-steroidal anti-inflammatory drugs on the disposition of methotrexate in 1998 Apr We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently taking the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and ibuprofen. The area under the curve, the total systemic clearance, the distribution volume, and the half-life of methotrexate in patients receiving concurrent NSAID therapy did not change significantly (at p < 0.05). Concurrent treatment with NSAIDs resulted in increased inter-patient variability of methotrexate concentration, possibly as a result of biochemical interactions; however, it does not appear clinically relevant. The data suggest that the NSAIDs do not significantly affect the disposition of methotrexate, contrary to some of the earlier reports.
11708409 The effect of low dose methotrexate on bone density. 2001 Nov OBJECTIVE: High dose methotrexate (MTX) has been linked with bone loss in oncology patients. However, it is unclear whether longterm low dose MTX used in the treatment of inflammatory arthritis is associated with bone loss. We compared the effect of low dose MTX on bone density in prospectively recruited patients with rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis (Ps/PsA). METHODS: Thirty RA patients and 30 Ps/PsA patients taking MTX were compared to controls not taking MTX (30 with RA, 27 Ps/PsA). Bone mineral density (BMD) of the radius, lumbar spine, trochanter, and femoral neck was measured using Lunar dual energy x-ray absorptiometry. Student t tests were used to detect differences in bone density (using Z scores) of the MTX group versus controls for both the RA and Ps/PsA groups. Analysis of covariance was used to examine for confounders including disease duration, disease activity, age, and sex. RESULTS: BMD of the radius/femoral neck/trochanter did not differ significantly between the MTX treated groups and controls when analyzed by Z scores. The mean difference between the MTX group and controls of the femoral neck was 0.040 (95% CI -0.40, 0.12) and 0.060 (95% CI -0.30, 0.15) for the RA and Ps/PsA groups, respectively. The absolute BMD of the lumbar spine (L2-L4) was higher in the RA MTX group than in controls. Analysis of covariance did not reveal an effect of study group on bone density. CONCLUSION: This study suggests that low dose MTX does not have a negative effect on bone density, at either cortical or trabecular sites.
9340952 [Combination therapy with remission-inducing drugs in chronic polyarthritis: 1996 update]. 1997 May Therapy of rheumatoid arthritis with a combination of several disease-modifying drugs aims to better control of the disease than achievable by monotherapy. Subsequent to a paper written two years ago, this publication reviews studies dealing with combination therapy issued mainly in 1995 and 1996. Most studies deal with MTX as one of the partners. Beneficial results were reported for the combination of methotrexate with antimalarials, cyclosporine or sulfasalazine. The triple combination of methotrexate with hydroxychloroquine and azathioprine is especially promising although the studies presented up to now are still insufficient for its final assessment, due to methodologic problems. Similarly, the value of the combination of sulfasalazine with injectable gold, of sulfasalazine with methotrexate and hydroxychloroquine, or of methotrexate with injectable gold is still uncertain.
9175024 Methotrexate use in systemic lupus erythematosus. 1997 Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.
10628065 Leflunomide for the treatment of rheumatoid arthritis. 1999 Leflunomide treatment appears to offer an alternative to methotrexate and sulfasalazine and is a welcome addition to the therapeutic armamentarium for treating active RA. Leflunomide treatment for more than 12 months results in clinically meaningful improvements in disease-specific measures of physical function. The phase 3 trials have shown leflunomide to be as effective as methotrexate and sulfasalazine and an option for initial DMARD therapy. As with all new agents, the long-term safety and value of leflunomide will be determined by use in the clinic.
9361155 Methotrexate use in rheumatoid arthritis. 1997 Nov To overstate the importance of methotrexate in the contemporary management of rheumatoid arthritis would be difficult. It has achieved this distinction because of its efficacy and tolerability. This article reviews the data on the efficacy and toxicity of methotrexate, discusses caveats for clinical use, examines the use of methotrexate in combination therapy, and speculates on the future use of methotrexate in rheumatoid arthritis.
10461474 Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease act 1999 Jul OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.
10464551 Relationship between serum RANTES levels and radiological progression in rheumatoid arthri 1999 Jul OBJECTIVE: The aim of this study was to evaluate the relationship between serum chemokines and the clinical and radiological response to a one-year course of methotrexate (MTX) in patients suffering from rheumatoid arthritis (RA). METHODS: Twenty out-patients suffering from active RA entered a one-year open prospective study on the effects of low dose MTX therapy. Plain radiographs of the hands and feet were taken at study entry and at the end of the follow-up, and were compared for the number of eroded joints. Serum levels of both C-X-C and C-C chemokines were obtained before the initation of MTX and after 6 and 12 months of treatment. RESULTS: The levels of serum RANTES before treatment were significantly higher in RA patients than in the controls and returned to normal levels after one year of treatment. Serum levels of the other chemokines were either in the normal range or undetectable. Twelve patients (60%) did not show any new eroded joints at the end of the follow-up period and were considered as radiological responders (RR). Serum levels of GRO-alpha and RANTES after 6 months of treatment were significantly higher among the patients with radiological progression than in RR patients. CONCLUSIONS: We observed high levels of serum RANTES in a series of RA patients during the active stage of the disease. MTX treatment significantly lowered the serum levels of RANTES, GRO-alpha and MCP-1. High levels of serum RANTES or GRO-alpha after 6 months of MTX treatment seem to be predictive of radiological erosions after one year.
9133966 Quantitative liver function in patients with rheumatoid arthritis treated with low-dose me 1997 Mar The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.
10589366 Aim for remission or "personal best" using combination DMARD therapy with methotrexate and 1999 Nov Combination disease-modifying antirheumatic drug therapy with methotrexate and hydroxychloroquine has changed the course of rheumatoid arthritis. Better management requires "front of the line" care, effective drug combinations, and a goal of "Personal Best." The Pincus phenomenon--the discrepancy between subjective satisfaction and objective progression--may be minimized in clinical practice by questionnaires and Snapshot.
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