Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 15301242 | Comparison of the baseline disease activity of early oligo- and polyarthritis in sequentia | 2004 Jul | OBJECTIVE: Many early arthritis clinics (EACs) have been started in the last decade in order to detect and treat rheumatoid arthritis early. The present study evaluates whether the disease activity at admission of patients with early oligo- and polyarthritis changed during the period 1993--1998 in two EACs in the Netherlands. METHODS: Patients were selected who were diagnosed after one year as having rheumatoid arthritis (RA) or oligo- or polyarthritis (UPA), had a symptom duration of less than 2 years, and were referred from two Dutch EACs between 1993 and 1998. The data from the two clinics were combined and stratified by referral year. Differences in baseline disease characteristics as well as changes in radiological and functional scores after two years of follow-up between referral years were analysed by ANOVA using Bonferroni corrected p levels. RESULTS: A total of 405 patients (66% females; median age 57 yrs (18-93): 80% diagnosed as RA, the remainder as UPA) were included in the study. The year-groups did not differ significantly in demographic characteristics or in the duration of complaints (median 6 months). The number of patients with a diagnosis of RA declined over the years, as did the mean baseline erythrocyte sedimentation rate (ESR), in RA and UPA patients. The functional status (Health Assessment Questionnaire: HAQ) was enhanced in 1998 compared with the previous years (p < 0.001). Radiographic progression (Sharp/van der Heijde score) after the 2-year follow-up decreased (p < 0.001) in the later referral years compared to the referral group of 1994. Disease modifying anti-rheumnatic drugs (DMARDs) were started in an earlier stage and the prescription rate of sulfasalazine and methotrexate increased over the years, whereas the number of patients not treated with DMARDs declined. CONCLUSION: The pattern of patient referral changed over 6 years towards fewer patients who fulfilled the RA diagnosis and a lower ESR (among UPA as well as RA patients), whereas the number of swollen joints and the duration of complaints remained the same. The radiological progression declined over time, probably due to less inflammation at the first visit and the increased use of DMARDs. | |
| 12056294 | Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrex | 2002 Apr | OBJECTIVE: To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). METHODS: We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. RESULTS: Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. CONCLUSIONS: With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event. | |
| 12722608 | [Anti-cytokines in the treatment of inflammation]. | 2003 Mar 1 | Tumour necrosis factor (TNF) alpha and interleukine 1 (IL-1) have a pro-inflammatory effect in all targets of the body. However, every inflammatory disease is characterized by a peculiar profile of secretion of cytokines. TNF alpha blocking agents are a major advance in the treatment of of rheumatoid arthritis, spondylarthropathies and Crohn disease. To date, the most common adverse events are reactions to infusions and reactivation of active tuberculosis with infliximab. Association of another immunosuppressive drug, such as methotrexate, decreases the first of these adverse events. IL1-RA is an inhibitor of IL-1 effects which have demonstrated its efficiency in rheumatoid arthritis. These anticytokines represent a dramatic progress in the treatment of inflammatory diseases but we have to stay very careful concerning the possible increased risk of infection or cancer. | |
| 17041340 | Assessment of renal function in rheumatoid arthritis: validity of a new prediction method. | 2002 Jun | Medical treatment of patients with rheumatoid arthritis (RA) requires assessment of renal function. Because determination of endogenous creatinine clearance from a 24-hour urine collection is an unreliable and time-consuming procedure, several formulae that predict creatinine clearance from clinical and serum parameters have been developed. However, because of muscular atrophy, these formulae show lower correlations with measured creatinine clearance in patients with RA than in the healthy population. Recently, a new formula has been derived from the large Modification of Diet in Renal Disease (MDRD) study and has been shown reliably to predict renal function in individuals with renal dysfunction. To investigate the validity of this method in the RA population, estimates of creatinine clearance were derived using the most commonly used Cockcroft-Gault formula and the new MDRD method in control subjects and patients with RA. Age, height, serum albumin, blood urea nitrogen, and creatinine clearance were similar in both groups, but patients with RA had a lower body weight as well as serum and urinary creatinine concentrations. In control subjects, both methods showed comparable correlations with measured creatinine clearance (r = 0.82 and 0.83, respectively). In patients with RA, the Cockcroft-Gault formula revealed a lower correlation (r = 0.69) with a moderate bias (mean error = -10.7) and prediction accuracy (mean squared error = 342). For the MDRD method, r was still lower at 0.41, the mean error was -18.9, and the mean squared error was 479. We conclude that in patients with RA, the Cockroft-Gault formula is preferable to predict creatinine clearance before use of drugs such as methotrexate or nonsteroidal anti-inflammatory drugs. | |
| 15609143 | Modelling the costs and effects of leflunomide in rheumatoid arthritis. | 2002 | This study investigated the cost-effectiveness of leflunomide (LEF) compared to methotrexate (MTX) and sulfasalazine (SSZ) in the United Kingdom. A Markov model was constructed using health states defined by Health Assessment Questionnaire score. The model is based on a cohort of patients with recently diagnosed definite RA who were followed for up to 15 years at nine rheumatology clinics in the UK. The treatment effect was calculated based on clinical trials comparing LEF to MTX (one international and one United States trial) and to SSZ (one international trial). Transitions between health states for the first 2 years of treatment were calculated from the clinical trials, while the extrapolation beyond the trial was based on the Early Rheumatoid Arthritis Study cohort, using an ordered probit model. This makes it possible to predict transitions for patients with similar characteristics (age, time since disease onset) as in the trials. Separate analyses were performed for each trial, and all analyses covered a 10-year timeframe. Using the US trial, LEF had slightly lower costs and better effects (44,017 and 4.307 pounds QALYs, compared to 44,988 and 4.158 pounds QALYs for MTX), while for the international trial this was reversed (34,070 and 4.487 pounds QALYs for MTX compared to 36,351 and 4.372 pounds QALYs for LEF). Compared to SSZ, the cost of using LEF was slightly lower, with an increase in QALYs (35,855 and 3.896 pounds QALYs compared to 36,731 and 3.721 pounds QALYs for SSZ). The two trials comparing LEF to MTX gave differing results. One possible reason for this is that MTX patients in the US trial were given folic acid, whereas in the international trial folate supplementation was not mandated. This may have reduced the effectiveness of MTX. In the UK it is standard practice to use folic acid with MTX, and therefore the results from the US trial may be more relevant for the UK. Compared to SSZ, the use of LEF appears to be cost-effective in the UK. | |
| 12528122 | Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile | 2003 Jan | OBJECTIVE: To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open-label, extended-treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept. METHODS: Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3-4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of > or =30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%. RESULTS: At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low-dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population. CONCLUSION: Children with severe, longstanding, methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well-tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections. | |
| 15176162 | Off-label uses and side effects of infliximab. | 2004 May | Infliximab was first approved by the FDA in 1998 as a treatment of moderately-to-severely active Crohn's disease in patients who have an inadequate response to conventional therapies, and fistulizing Crohn's disease. In November 1999 the FDA approved it for use in rheumatoid arthritis with methotrexate, and further expanded this indication in December 2000. It appears to be a promising agent in the treatment of a variety of inflammatory diseases, psoriasis in particular. A MEDLINE search was performed for "infliximab" in February of 2004, and the 1,116 articles found were reviewed. Approximately 200 articles were identified that contained references to the treatment with infliximab of skin disease, off-label uses, systemic diseases with cutaneous manifestations, and systemic and cutaneous side effects. These articles were reviewed and their contents summarized. Infliximab has been proven in well-controlled trial trials to ameliorate inflammatory bowel disease, rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. Anecdotal reports report it useful in treating the cutaneous manifestations and associations of inflammatory bowel disease, Behçet's disease, graft versus host disease, Sjogren's syndrome, refractory sarcoidosis, and a variety of other conditions. Its notable side effects include an increased risk of the induction of infections (e.g., tuberculosis). Infliximab is a very promising medication in the treatment of inflammatory dermatological conditions and should be used in larger scale trials of more diseases. | |
| 15775150 | [Inhibition of joint destruction by methotrexate]. | 2003 Jun | Methotrexate (MTX) plays an important role in treatment of rheumatoid arthritis (RA). It significantly reduce expected radiographic progression. Comparing with other traditional disease-modifying anti-rheumatic drugs (DMARDs), MTX slow radiographic progression during the first 2 years. Since combination with anti-tumor nectosis factor alpha (TNF-alpha) therapy has been shown to be effective for the early supression of disease activity, it could be usefull to minimize bone destruction in RA. | |
| 15228619 | Treating psoriatic arthritis: how effective are TNF antagonists? | 2004 | Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy that commonly appears after the onset of the characteristic cutaneous lesions. This complication affects about 40% of patients with moderate to severe cutaneous disease. Analysis of synovial fluid and tissue in patients with PsA demonstrates a profile of high levels of tumor necrosis factor (TNF) plus other cytokines similar to those seen in patients with rheumatoid arthritis (RA). In the past, medical management of patients with this disease consisted of treatment with nonsteroidal anti-inflammatory agents. Patients with more severe disease have tried a number of different disease-modifying drugs including methotrexate, azathioprine, and gold salts. However, there is no evidence that these agents can arrest the progress of structural joint damage. Infliximab and etanercept are TNF antagonists that have demonstrated significant efficacy and safety in patients with RA. Clinical trials with these two agents in patients with PsA have shown significant improvement in the rheumatologic and cutaneous manifestations of the disease. | |
| 12894136 | Evaluation and management of psoriatic arthritis: the role of biologic therapy. | 2003 Aug | Clinicians often view psoriatic arthritis (PsA) as a rather minor arthritic disorder because many are unaware of the substantial damage, disability, and reduced quality of life that patients with this disease can suffer. Compared with better-studied arthritic conditions, such as rheumatoid arthritis (RA) with well-known consequences of disease progression, PsA does not elicit the same urgency to treat early and aggressively. This is largely owing to the lack of predictive epidemiologic data regarding disease progression in PsA. However, numerous studies indicate that PsA and RA are comparable in terms of overall severity of joint involvement and disability over equivalent disease duration. Many of the drugs traditionally used for PsA therapy are also used to treat RA, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, methotrexate (MTX), sulfasalazine, cyclosporine, etretinate, auranofin, intramuscular gold, and azathioprine. All of these drugs have significant risk of toxicity over long-term use, and all provide variable efficacy. This makes it difficult for clinicians to make sound risk-benefit assessments regarding treatment or nontreatment of PsA, because the risks of disease progression cannot be weighed against the risks of therapy. The newer biologic antirheumatic drugs appear to combine greater efficacy of treatment with significantly less toxicity by targeting specific mediators involved in the pathogenesis of PsA. | |
| 12749755 | Role of novel biological therapies in psoriatic arthritis: effects on joints and skin. | 2003 | Psoriatic arthritis (PsA) is a partly debilitating disease that may affect small and large joints and the spine. Patients with PsA are divided into different subgroups according to joint involvement and their disease may be classified as part of the spectrum of spondyloarthritides or seronegative rheumatoid arthritis. Traditional treatment comprises nonsteroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate and cyclosporin. On the basis of the very recent studies performed in the US and Germany, patients with severe disease can be treated with anti-tumour necrosis factor (TNF) therapy. Biologicals such as etanercept and infliximab have been used successfully to treat PsA. While etanercept is a 75kD TNF receptor fusion protein that binds to TNFalpha and TNFbeta, infliximab is a chimeric monoclonal antibody that binds to TNFalpha both in its soluble form in the serum and on the cell membrane. Adalimumab is a fully humanised antibody recognising TNFalpha that has not been tested in PsA to date. Another biological agent, alefacept, is directed against the adhesion molecule lymphocyte function-associated antigen (LFA)-2, which is known to interfere with T-cell activation. Alefacept has been shown to be efficacious in a limited number of patients with PsA. Taken together, there has been definite recent progress in the treatment of PsA. Severely affected patients may especially have substantial benefit from therapy with biologicals directed against TNFalpha and other targets. | |
| 12180746 | Gynecomastia and sexual impotence associated with methotrexate treatment. | 2002 Aug | Methotrexate (MTX) is the disease modifying antirheumatic drug most frequently used for rheumatoid and psoriatic arthritis (PsA). Several reports associate sexual dysfunction to MTX use. We describe 2 cases of sexual impotence and gynecomastia in patients with PsA treated with MTX. Although the mechanism underlying MTX induced sexual dysfunction is unknown, the potential consequences should be taken in account in view of the steady increase in the number of patients. | |
| 12695164 | Primary Sjögren's syndrome associated agranulocytosis: a benign disorder? | 2003 May | OBJECTIVE: To report on an uncommon association of agranulocytosis in primary Sjögren's syndrome (SS). METHODS: The clinical, haematological, and immunological features of seven patients with primary SS associated with a chronic (>6 months) agranulocytosis, and the outcome of the patients, were analysed. RESULTS: Patients were white women with an unexplained agranulocytosis. They all had non-erosive arthritis and three had a thrombocytopenia or Evan's syndrome. In three patients, transient or durable expansion of T lymphocytes was present in the peripheral blood or in the bone marrow, but evolved independently from neutrophil counts. There was no paroxysmal nocturnal haemoglobinuria clone or antibodies to neutrophil surface antigens. In vitro bone marrow culture was normal (four patients) or showed a decrease in colony forming unit-granulocyte monocyte (CFU-GM) and colony forming unit-erythroblast (CFU-E) (one patient). Serum levels of soluble Fas ligand (sFasL) were normal, and granulocyte-colony stimulating factor (G-CSF) concentrations were either normal or raised. One patient was treated with steroids associated with intravenous immunoglobulins and achieved a lasting response. Two other patients were treated with steroids and methotrexate, with poor efficacy. Short courses of subcutaneous G-CSF produced a transient and mild response in all three patients. Complete recovery of the neutrophils occurred temporarily during pregnancy in two patients. After a mean follow up of 34.8 months (range 6-139) all patients were alive and none developed serious infections. CONCLUSION: A subset of patients with primary SS and non-destructive arthritis may develop a chronic but well tolerated agranulocytosis that is usually poorly responsive to steroids and oral methotrexate. | |
| 14576992 | Inclusion body myositis in connective tissue disorders: case report and review of the lite | 2003 Oct | We report a patient with systemic lupus erythematosus (SLE) and secondary Sjögren's syndrome (SS) who developed inclusion body myositis (IBM) which, contrary to the typical presentation of this disorder, was symmetrical in nature although the diagnosis was only made after electron microscopy was performed. Therapy with increased doses of methotrexate proved to be beneficial, with the patient having full recovery after 8 months of therapy. It appears that a subset of IBM may be related to autoimmune disorders, an issue that was disputed in the past, and these patients may have a better prognosis than typical IBM patients. This is the first case report of IBM in a patient who had the dual diagnosis of SLE and SS. | |
| 15488696 | Pharmacoepidemiology and rheumatic disorders. | 2004 Nov | This article reviews the application of pharmacoepidemiology in the evaluation of drugs that are used commonly for rheumatic disorders. Data sources and methodology considerations for these studies are highlighted. The topics that are covered included the safety evaluation of nonsteroidal ant-inflammatory drugs, adverse pregnancy outcomes of pharmaceutical agents, gastroduodenal safety of alendronate, long-term beneficial effects of methotrexate for rheumatoid arthritis, and drug use study. | |
| 15461871 | Infliximab monotherapy for refractory psoriasis: preliminary results. | 2004 Sep | Tumour necrosis factor (TNF)-alpha plays an important role in the pathogenesis of psoriasis. Infliximab is an anti-TNF-alpha chimeric monoclonal antibody, which is licensed for the treatment of rheumatoid arthritis and Crohn's disease. Some reports have shown the efficacy of infliximab, either in monotherapy or in combination with methotrexate, for the treatment of psoriatic arthropathy and psoriasis. The efficacy and tolerability of infliximab monotherapy was evaluated in 29 patients with moderate to severe psoriasis, unresponsive to conventional treatments. Fourteen patients suffered from concomitant arthropathy. Patients received intravenous infliximab, 5mg/kg, at weeks 0, 2, and 6. After this 3-dose-induction regimen, patients were followed-up at monthly intervals and retreated with a single-dose infusion in case of relapse of signs and symptoms. Clinical assessment was performed using the psoriasis area and severity index (PASI) to monitor psoriasis activity; pruritus and joint pain were assessed on a scale of 0 to 3. A marked improvement of skin lesions and subjective symptoms was noted in the majority of patients; an excellent reduction of PASI score (> or =75%) was observed in 13.8% of cases at week 2, 71.4% at week 6 and 78.6% at week 10. During the follow-up period, some patients maintained satisfactory clinical results without requiring any additional infusions. In general, skin lesions showed a trend towards a more prolonged and sustained improvement as compared with subjective symptoms. Treatment was well tolerated and no serious adverse events occurred. | |
| 15775151 | [Leflunomide: clinical effectiveness and mechanism of action]. | 2003 Jun | Leflunomide is a new immunomodulatory agent by selectively inhibiting the de novo pyrimidine synthesis. Its active metabolite (A77 1726) is highly bound to plasma protein and has a long half life. Through several large trials describing its efficacy and safety including retardation of radiographic progression in comparison with both sulfasalazine and methotrexate and with placebo have been published in Europe and the United States, leflunomide was shown to improve primary and secondary outcome measures with satisfactory safety profile. The most common treatment-related adverse reactions were diarrhea, nausea, and abnormal plasma liver enzyme levels. Leflunomide may be a useful addition to the current management of rheumatoid arthritis. | |
| 14610911 | Immunosuppressants in advanced clinical development for organ transplantation and selected | 2003 May | Immunosuppressants dampen the immune response or restore balance among immune system components. They are primarily used to prevent allograft rejection after organ transplantation and to prevent or treat disease flares in autoimmune diseases. Immunosuppressants available at present include the calcineurin inhibitors (cyclosporin, tacrolimus), antimetabolites (azathioprine, leflunomide, methotrexate, mycophenolate mofetil), antiproliferatives (sirolimus), monoclonal antibodies to T lymphocyte (basiliximab, daclizumab, muromonab-CD3) and anticytokines (anakinra, etanercept, infliximab). The immunosuppressive market grows at a rate of > 10% yearly, with total sales in 2001 of US$2.7 billion. Immunotherapy in transplantation and autoimmune diseases is tending towards the use of multi-drug regimens tailored for the individual patient. At least 23 new immunosuppressants are currently in advanced clinical testing or preregistration, and can be divided into three groups. First, emerging drugs targeting intracellular ligands in immune cells are primarily analogues of currently-marketed agents, which attempt to provide improved pharmaceutical or safety profiles compared with the prototype compound. They are largely being developed in organ transplantation. Second, emerging drugs targeting cell surface ligands on immune cells attempt to antagonise novel molecular sites to interfere with immune cell activation via costimulatory signals, immune cell adhesion to tissues or the vasculature and immune cell trafficking. These agents are being primarily developed in rheumatoid arthritis, psoriasis and/or multiple sclerosis. Finally, emerging drugs acting as anticytokines, which largely follow on from the success of those on the market, by antagonising the function of tumour necrosis factor or a narrow selection of interleukins. All are being assessed in rheumatoid arthritis. Drug development of immunosuppressants is increasingly attempting to intervene in disease progression over the long term. These efforts bring with them trial design and regulatory issues, such as what markers can be used as trial outcome measures, over what duration do trials need to be conducted and what labelling claims are allowed. With the intensive activity in this field, it is likely that several new drugs will reach the market in the coming decade. One caveat, however, is that emerging immunosuppressants that are likely to capture a reasonable share of this increasingly-fragmented market must demonstrate the ability to achieve disease remission or long-term slowing of disease progression. | |
| 15627439 | R-130823, a novel inhibitor of p38 MAPK, ameliorates hyperalgesia and swelling in arthriti | 2005 Jan 4 | We found that a novel compound, R-130823 {2-(4-fluorophenyl)-4-(1-phenethyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole}, had highly selective inhibition against mitogen-activated protein kinase p38alpha (IC50=22 nM). The release of tumor necrosis factor-alpha, interleukin-1beta, -6 and -8 was inhibited in lipopolysaccharide-stimulated human blood pretreated by R-130823, with IC50 values of 0.089, 0.066, 0.95 and 0.16 microM, respectively. R-130823 reduced the established hind paw swelling in rat adjuvant-induced arthritis, while methotrexate showed no suppression. In the same model, R-130823 ameliorated adjuvant-induced hyperalgesia with rapid onset and long duration comparable to a cyclooxygenase-2 inhibitor, celecoxib. In murine collagen-induced arthritis, R-130823 blocked the progress of arthritis when administered just after the onset of the arthritis. Histological analysis of the knee joints showed that proliferation of fibroblasts and synoviocytes and infiltration of neutrophils were ameliorated. In conclusion, R-130823 is expected to be an efficacious treatment for rheumatoid arthritis by blocking the p38 pathway. | |
| 12487726 | Decreased activity of hepatic P-glycoprotein in the isolated perfused liver of the adjuvan | 2002 Nov | 1. We investigated the hepatobiliary transport of doxorubicin in the isolated perfused liver prepared from the adjuvant arthritis rat, an animal model for rheumatoid arthritis, to examine the hepatic P-glycoprotein activity in the adjuvant arthritis rat. 2. Liver was isolated from the normal and the adjuvant arthritis rat and perfused for 60 min with recirculating buffer and the perfusate and bile samples were collected at timed interval. 3. The elimination of doxorubicin in the adjuvant arthritis rat tended to be reduced, but it was not significantly different from the normal rat. Biliary clearance (CL(bile)) in the normal rat was 1.93 +/- 0.48 ml min(-1), whereas, CL(bile) in the adjuvant arthritis rat was significantly decreased to 0.40 +/- 0.13 ml min(-1). 4. CL(bile) was markedly decreased to about 0.15 ml min(-1) in the presence of 100 microM verapamil in both types of rat. Methotrexate treatment had no effect on CL(bile) in both the normal and adjuvant arthritis rat (2.18 +/- 0.22 and 0.47 +/- 0.22 ml min(-1), respectively). 5. The results suggest that the hepatic P-glycoprotein activity was markedly decreased in the adjuvant arthritis rat and the effect of methotrexate on the hepatic P-glycoprotein activity did not corresponded to its anti-inflammatory effect. |