Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11578013 Changes in therapy of rheumatoid arthritis during the period 1979 to 1996. 2001 OBJECTIVE: To evaluate the use of disease modifying antirheumatic drugs (DMARDs), cytotoxic agents, and corticosteroid therapy in patients diagnosed with rheumatoid arthritis (RA) in two periods, 1979 to 1987, and 1988 to 1996. MATERIALS AND METHODS: Review of the records of 788 patients with RA diagnosed at the Department of Rheumatology, the University Hospital of Tromsø. RESULTS: We found a significant increase in the proportion of patients who started with auranofin, sulfasalazine, methotrexate, and corticosteroids in 1988 1996 compared to 1979 1987. The initiation of use of gold salts, antimalarials, and D-penicillamine declined significantly from the first to the second period. CONCLUSION: Patients diagnosed with RA between 1988-1996 were treated more actively than patients diagnosed in the period 1979-1987. During 1988 to 1996 auranofin, sulphasalazine, methotrexate, and corticosteroids replaced gold salts, antimalarials, and D-penicillamine.
11171680 Methotrexate and early postoperative complications in patients with rheumatoid arthritis u 2001 Mar OBJECTIVES: To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery. DESIGN: A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery. SUBJECTS: 388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery. MAIN OUTCOME MEASURES: Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery. RESULTS: Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p<0.003) or group C (p=0.026). At six weeks after surgery there were no flares in group A, six flares in group B (8%), and six flares in group C (2.6%). Logistic regression analysis of the overall surgical complication rate in all the patients with RA studied showed that methotrexate, whether continued or discontinued before surgery, did not increase the early complication rate in the patients with RA who underwent elective orthopaedic surgery. Other drugs-penicillamine, indometacin, cyclosporin, hydroxychloroquine, chloroquine, and prednisolone-all did significantly increase the risk of infection or surgical complication after elective orthopaedic surgery. The risk of surgery was also increased in the presence of intercurrent chronic diseases-diabetes, hypertension, bronchiectasis, psoriasis, asthma, and ischaemic heart disease. CONCLUSION: Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.
9456017 Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthri 1997 Nov Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5 mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluorescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.
10646486 Rheumatoid arthritis: new developments in the use of existing therapies. 1999 Nov Combination therapy with methotrexate may be the newest standard to which future therapies for rheumatoid arthritis are compared. Many questions remain to be answered regarding the appropriateness of such combination therapies for specific patients and clinical situations, and the optimal therapeutic combinations. Other unanswered questions regarding combination therapy include the need for appropriate monitoring, long-term safety and cost-benefit implications. Future research is needed to clarify the role of biological response modifiers (e.g. anti-tumour necrosis factor therapies) and matrix metalloproteinase inhibitors, both as components of and alternatives to methotrexate combination regimens.
11304666 Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1: the olde 2001 Mar Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy and may be of comparatively recent, New World origin. Apart from the symptom-relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been in use since antiquity for musculoskeletal pain and inflammation, only a dozen drugs or drug classes--the disease-modifying antirheumatic drugs--are currently in common use in rheumatoid arthritis. Development of these drugs has been a notable achievement of the 20th century. Some were developed serendipitously (glucocorticoids, antimalarials), some were the product of faulty reasoning (gold, D-penicillamine), and others were applied for plausible reasons but whose mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority were originally applied on the basis of actions that remain germane to the pathophysiology of rheumatoid arthritis as currently understood (azathioprine, cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more recently introduced and effective agents. The practical use of these drugs is determined by efficacy-toxicity considerations, which have also driven the recent development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs.
10796461 Auranofin versus placebo in rheumatoid arthritis. 2000 BACKGROUND: Auranofin is an oral gold compound used for the treatment of rheumatoid arthritis RA. The use of auranofin has declined in the past few years, perhaps due in part to conflicting results from different studies. OBJECTIVES: To estimate the short-term efficacy and toxicity of auranofin for the treatment of (RA) SEARCH STRATEGY: We searched MEDLINE and EMBASE up to December 1998, the Cochrane Controlled Trials Register (CCTR) version 4, 1998, and the Cochrane Musculoskeletal Group Specialized Register. A hand search was also done of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing auranofin against placebo in patients with RA DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using a validated assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. The weighted mean difference (WMD) was used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. In the presence of heterogeneity, random effects models were used. Otherwise, the data was pooled assuming fixed effects. MAIN RESULTS: A statistically significant benefit was observed for auranofin when compared to placebo for tender joint scores, pain, patient and physician global assessments and ESR. The SMD between treatment and placebo was -0.39 (95% CI -0.54, -0.25) for tender joint scores, -0.08 (95% CI -0.22, -0.07) for swollen joint scores, and the WMD was -4.68 (95% CI -6.59, -2.77) for pain scores and -9.85mm (95% CI -16.46, -3.25) for ESR. Withdrawals from adverse reactions were 1.5 times higher in the auranofin group OR = 1.52 (95% CI 0.94, 2.46) but this result was not statistically significant. Patients receiving placebo were three times more likely to discontinue treatment because of lack of efficacy than patients receiving auranofin: OR=0.31 (95% CI: 0.21, 0.44). REVIEWER'S CONCLUSIONS: Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.
10646494 Recapitulation of the round-table discussion--assessing the role of anti-tumour necrosis f 1999 Nov Clinical trials specifically targeting and neutralizing the cytokine, tumour necrosis factor (TNF), have recently provided evidence of efficacy and a promise of a novel approach for the treatment and management of rheumatoid arthritis (RA). With the evolving emergence of anti-TNF therapeutics, several unresolved issues have come to light, including the assessment of safety and efficacy of current therapies, study design for new agents and cost-benefit issues. During an international meeting of leading rheumatologists and specialists, the majority opinion regarding the use of anti-TNF therapy was that these agents are most appropriate in patients with active disease who have insufficient response to methotrexate, which is presently considered the standard for RA treatment. Anti-TNF therapy was also recommended in patients with active disease unable to tolerate methotrexate therapy, or who have not responded to at least two other disease-modifying anti-rheumatic drugs (DMARDs). In patients with RA who have serious infection or malignancy, the use of anti-TNF therapies was not advised. Time, experience and clinical data from recently completed and currently ongoing studies of infliximab and etanercept, which will be available in the future, will help determine the ultimate role of such targeted therapeutics. Additional data on anti-TNF therapeutics as monotherapy or in various combinations are still needed to achieve maximum disease control safely with currently available DMARDs.
11993724 Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthr 2001 Nov Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.
11367869 Antioxidants as adjuvant therapy in rheumatoid disease. A preliminary study. 2001 The aim of the present study was to assess the therapeutic value of adding a high dose of vitamin E or an antioxidant combination to the treatment regimen of the rheumatoid disease. The study was carried out on 30 patients with rheumatoid disease diagnosed according to the criteria of American Rheumatism Association (ARA), subvided into three equal groups. Patients in group I received a standard treatment of intramuscular methotrexate (CAS 59-05-2; 12.5 mg/week), oral sulphasalazine (CAS 599-79-1; 0.5 g b.i.d.) and indometacin (CAS 53-86-1; 100 mg suppository at bed-time). In group II the patients received the standard treatment plus a combination of antioxidants. Patients in group III received a high dose of vitamin E (400 mg t.i.d.) in addition to the standard treatment. The disease state was evaluated using Ritchle's articular score index and the duration of morning stiffness. Laboratory evaluations included the rheumatoid factor, erythrocyte sedimentation rate (ESR), plasma levels of vitamin E and malonedialdehyde (MDA), and the activity of glutathione peroxidase (GPx). In the group receiving the standard regimen, the patients started to feel tangible improvement by the end of the second month. With adjuvant therapy of either the antioxidant combination or a high dose of vitamin E the symptoms of arthritis were better controlled from the first month. By the end of the second month, the values of the three monitoring tests were significantly decreased indicating better control of the disease. The percentage increase in the activity of GPx was highest in patients taking the antioxidant combination and least in those taking the standard treatment. The decrease in plasma MDA followed the same pattern. With adjuvant therapy, the vitamin E level in plasma increased with the duration of treatment. The results obtained in the present study are encouraging. The clinical improvement and the shift in the disease indices towards normal make the use of antioxidants as adjuvant therapy in rheumatoid disease worth pursuing.
11039841 The presence of HLA-DR B1 shared motif does not influence cyclophosphamide and methotrexat 2000 Jul In the present study we investigated the relation between cyclophosphamide and methotrexate toxicity and the presence of HLA- DR B1 alleles in rheumatoid arthritis patients. Seventy-eight such patients (67 women and 11 men) were observed for 12 months. Eighteen were treated with intravenous cyclophosphamide, 28 with oral methotrexate, and 32 with intramuscular gold salts. The prevalence of this shared motif was higher in the study population than in the healthy controls. However, detailed observations did not demonstrate a relation between particular genotype and drug intolerance. Based on the obtained findings we concluded that HLA-DR B1 typing cannot affect cyclophosphamide or methotrexate tolerance in rheumatoid arthritis patients. However, taking into account the relatively small number of patients expressing single genotype, further studies are recommended.
10685792 Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refrac 2000 Feb OBJECTIVE: To investigate the effect of cyclosporine on cytokine production, especially on T helper 1 (Th1) and T helper 2 (Th2) type cytokines, in patients with rheumatoid arthritis (RA). METHODS: A 16 week randomized, double blind, placebo controlled study of cyclosporine (2.5 to 4 mg/kg/day) was conducted in 40 patients with severe, refractory RA who had residual inflammation and disability despite partial responses to prior maximal tolerated dose of methotrexate (MTX; < 15 mg/week) and low dose prednisone (< 10 mg/day). Clinical and laboratory variables, and circulating levels of interleukin 2 (IL-2), IL-4, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) measured by ELISA were compared between patients (cyclosporine group) treated with cyclosporine plus MTX and those (placebo group) treated with placebo plus MTX at entry and at 16 weeks. RESULTS: At 16 weeks, the cyclosporine group (n = 17), compared with the placebo group (n = 17), had greater decreases in tender joints, swollen joints, patient global assessment, patient self-assessed disability, and C-reactive protein, as well as having more patients with > 20% improvement. Comparison of circulating cytokines at entry and at 16 weeks showed significant decreases of IL-2 (median -61 vs 7 pg/ml; p = 0.004) ("+" denotes increase, "-" denotes decrease), IL-12 (median -313 vs -14 pg/ml; p = 0.002), TNF-alpha (median -55 vs 5 pg/ml; p < 0.001), and IFN-gamma (median -21 vs 5 pg/ml; p = 0.003), and a significant increase of IL-10 (median 55 vs -12 pg/ml; p < 0.001) in the cyclosporine group compared with the placebo group. The degree of IL-10 increases correlated strongly with the degree of IL-12 decreases in the cyclosporine group (r = 0.572, p = 0.016). However, there was no change in circulating IL-4 between the 2 groups. Within the cyclosporine group, the improved patients (n = 10) compared to the non-improved patients (n = 7) had a greater increase in circulating IL-10 (median 172.0 vs 85.2%; p = 0.01). The rate of increase of IL-10 strongly correlated with the rate of improvement of joint scores (r = 0.718, p = 0.001) after administration of cyclosporine. CONCLUSION: Our results suggest that the therapeutic effect of cyclosporine is achieved by correcting a Th1/Th2 imbalance (a shift of Th1 type to Th2 type), which may be involved in the pathogenesis of RA; and that circulating IL-10 is useful to assess the clinical improvements in patients with RA after administration of cyclosporine.
11034702 Cyclophosphamide for treating rheumatoid arthritis. 2000 OBJECTIVES: To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.
10695684 Cytokine blockade as a new strategy to treat rheumatoid arthritis: inhibition of tumor nec 2000 Feb 28 Rheumatoid arthritis (RA) is a common, frequently severe, chronic inflammatory disease. Although the cause of RA remains unknown, recent advances in understanding its pathogenesis have been substantial. Despite the use of a variety of medications, particularly methotrexate, treatment of RA is not fully effective in most patients. Until recently, insights into inflammatory mechanisms in RA had not been successfully translated into novel classes of therapeutic agents. This gap now will likely be bridged in the form of a new strategy for treating RA-cytokine blockade. Although a variety of cytokines are important in the pathogenesis of RA, tumor necrosis factor (TNF) seems to play a pivotal role. Neutralizing TNF in patients with RA, by means of soluble TNF receptors or anti-TNF monoclonal antibodies, has proven to be a powerful means of controlling disease activity. Studies are in progress to obtain additional information regarding long-term safety of TNF blockade and its effects on disease progression.
11508582 Methotrexate inhibits rheumatoid synovitis by inducing apoptosis. 2001 Aug OBJECTIVE: To clarify the pharmacological action of methotrexate (MTX) on the synovium of patients with rheumatoid arthritis (RA) using severe combined immunodeficient (SCID) mice in which human RA synovial tissue had been grafted (SCID-HuRAg). METHODS: One month after engraftment of human RA tissue into SCID mice, MTX (0.3 mg/kg) was administered orally, then the appearance of apoptosis in the grafted tissue was examined by TdT mediated dUTP nick end labeling (TUNEL) staining and electron microscopy at various time points after MTX administration. In cultured synovial cells, synovial apoptotic changes after MTX treatment were studied by agarose gel electrophoresis and flow cytometric analysis. To compare the histological changes induced by MTX with those induced by other disease modifying antirheumatic drugs (DMARD) and a nonsteroidal antiinflammatory drug, histological examination of the grafted synovial tissues from SCID-HuRAg mice was conducted after 4 weeks of oral administration of MTX (0.3 mg/kg/week), salazosulfapyridine (30 mg/kg/day), auranofin (0.2 mg/kg/day), bucillamine (10 mg/kg/day), or indomethacin (2 mg/kg/day). RESULTS: A significant decrease in the number of inflammatory cells was observed in the grafted synovial tissue of MTX treated SCID-HuRAg. A similar antiinflammatory effect was not observed with the other DMARD. Induction of apoptosis was noted with MTX treatment but not with the others. The pro-apoptotic effect of MTX was also observed in synovial cell cultures. CONCLUSION: MTX induces apoptosis in RA synovium that, in turn, may contribute to its antiinflammatory effect on RA synovitis.
11583065 Etanercept in rheumatoid arthritis. 2001 Jul Etanercept (Enbrel, Immunex Corporation, Seattle, Washington, USA) is a new biological disease-modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA). It is one of two TNF-alpha blockers to be licensed for the treatment of active RA and is classified as a recombinant human soluble TNF receptor. The drug competitively inhibits the binding of TNF to cell surface receptors and thus renders TNF biologically inactive. In doing so, etanercept inhibits the pro-inflammatory effects of TNF and results in a reduction of joint inflammation in patients with RA. Etanercept has shown a statistically significant reduction in swollen and inflamed joint counts, biochemical markers such as erythrocyte sedimentation rate and C-reactive protein and shown significant improvements in quality of life measures (HAQ and global assessment scores) in all studies. In early disease, etanercept has shown a reduction in joint space narrowing equal to methotrexate (MTX) and a reduction in the appearance of new erosions significantly better than MTX after 1 year of treatment. Etanercept has a rapid onset of action which is significantly faster than standard DMARDs. Etanercept was well-tolerated in clinical trials. The commonest side effects were injection site reactions and upper respiratory tract infections. Etanercept therapy has resulted in serious infections in some patients and should be used with caution in any patient with a history of recurring infections or with disease states that may predispose to infections. In summary, etanercept is an effective and well-tolerated agent that is a significant breakthrough in the treatment of this disabling condition.
9336420 Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate fo 1997 Oct OBJECTIVE: To determine whether the clinical benefit and favorable safety profile previously noted with the combination of cyclosporine (CSA) and methotrexate (MTX) given for 24 weeks in patients with rheumatoid arthritis (RA) would be maintained for a further 24 weeks, and whether the addition of CSA in patients who had previously been randomized to receive placebo + MTX would result in clinical benefit. METHODS: Eligible subjects from the initial study (weeks 0-24), in which the addition of placebo or CSA to MTX therapy was compared in patients with RA that was partially responsive to MTX, were enrolled. Patients who had received CSA + MTX continued this regimen for a further 24 weeks (weeks 24-48) (group 1; n = 48), and patients who had initially received placebo + MTX now received CSA + MTX for 24 weeks (weeks 24-48) (group 2; n = 44), in an open-label extension study. The primary outcome measures were the number of tender joints, number of swollen joints, physician and patient global assessments, pain, functional disability as measured by the modified Health Assessment Questionnaire, and erythrocyte sedimentation rate. RESULTS: Of the 92 patients enrolled, 80 (87%) completed the extension study. In patients in group 1, the clinically and statistically significant improvement in response outcomes previously noted at week 24, ranging from 25% to 50%, was maintained through week 48. In patients in group 2, the addition of CSA resulted in significant clinical improvement. By week 48, most outcome measures in group 2 patients were similar to those in group 1 patients. CSA treatment resulted in a small increase in serum creatinine levels, but only 1 patient was withdrawn from the study for this reason. CONCLUSION: The clinical improvement previously observed in patients treated with the CSA + MTX combination for 24 weeks was maintained for 24 subsequent weeks, without serious adverse effects, and was also observed in the patients whose treatment was switched from placebo + MTX to CSA + MTX.
11155812 Low dose prednisolone therapy (LDPT) retards radiographically detectable destruction in ea 2000 OBJECTIVE: To test if continuous LDPT decreases radiographically detectable joint destruction in early RA. METHODS: Patients with active RA (< 2 years from symptom onset) were treated with prednisolone 5 mg daily or placebo for 2 years in a double blind, randomized, multi-center study. At the same time in all patients DMARD treatment with either gold sodium thiomalate (GSTM) or methotrexate (MTX) was started; in the case of side effects or inefficacy the medication could be switched to the other DMARD. Radiographs of hands and forefeet were taken at baseline and after 6, 12 and 24 months. All radiographs were evaluated by one observer (S.W.) knowing the time sequence of the film but unaware of the patient identity or treatment using the Ratingen score and van der Heijde's modification of Sharp's method. RESULTS: 196 patients were included; 76 patients completed the study per protocol. Of these patients 34 were treated with prednisolone, 42 with placebo, 48 initially with GSTM, 28 with MTX. 17 patients switched from GSTM to MTX, 1 from MTX to GSTM. The mean values of the radiographic scores of both groups are given in the table. During the first year, especially during the first 6 months, the radiographic progression within the prednisolone group was significantly lower than in the placebo group: the Sharp erosion score increased by 0.4% of the maximum possible score during the first and the second 6 months in the prednisolone group, while in the placebo group there was an increase of 1.8% during the first 6 months and 0.8% during the second 6 months. During the second year the progression was significantly lower (-0.1% in the prednisolone group, 0.2% in the placebo group). After 24 months the total score had increased by 2.6% of the maximum score in the placebo group and by 1.1% in the prednisolone group. The results of the completers were confirmed by the intention-to-treat analysis (80 patients in the prednisolone group, 86 patients in the placebo group). CONCLUSION: Continuous low dose prednisolone treatment with 5 mg daily over 2 years administered in addition to conventional DMARD treatment with MTX or GSTM decreases radiographic progression in early RA. The results of the study also show that in the placebo group there is a sharp decrease of the progression after 6-12 months as a result of the DMARD treatment. During the second year there is nearly no progression in this group. The data of the "completers" are confirmed by the analysis of the "intention to treat" population.
10878293 Methotrexate use in rheumatoid arthritis. A Clinician's perspective. 2000 May Aminopterine, a precursor of methotrexate (MTX), was first used for the treatment of rheumatoid arthritis (RA) in 1951 [Gubner, R., 1951. Therapeutic suppression of tissue reactivity: I. Comparison of the effects of cortisone and aminopterin. Am. J. Med. Sci. 221, 169-175; Gubner, R., August, S., Ginsberg, V., 1951. Therapeutic suppression of tissue reactivity: II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am. J. Med. Sci. 221, 176-182.]. Corticosteroids, and to some extent cyclophosphamide, took MTX out of the rheumatologist's armamentarium until the late 1970s-early 1980s when the toxic profile of these compounds became apparent. By the mid 1980s, four randomized clinical trials (RCTs) had proven beyond doubt the beneficial effects of MTX when administered to patients with established disease who had failed to respond to other compounds such as gold salts and D-penicillamine [Thompson, R.N., Watts, C., Edelman, J., Esdaile, J., and Russell, A.S., 1984. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J. Rheumatol. 11, 760-763; Andersen, P.A., West, S.G., O'Dell, J.R., Via, C.S., Claypool, R.G., and Kotzin, B.L., 1985. Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann. Intern. Med. 103, 489-496; Weinblatt, M.E., Coblyn, J.S., Fox, D.A., Fraser, P.A., Holdsworth, D.E., Glass, D.N., and Trentham, D.E., 1985. Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med. 312, 818-822; Williams, H.J., Willkens, R.F., Samuelson, C.O.J., Alarcón, G.S., Guttadauria, M., Yarboro, C., Polisson, R.P., Weiner, S.R., Luggen, M.E., Billingsley, L.M., Dahl, S.L., Egger, M.J., Reading, J.C., and Ward, J.R., 1985. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum. 28, 721-730.]. Subsequently, these four trials were included in a meta-analysis and the drug was approved by the Food and Drug Administration for use in RA [Health and Public Policy Committee, H.P.P.C. and American College Physicians, A.C.P., 1987. Methotrexate in rheumatoid arthritis. Ann. Intern. Med. 107, 418-419; Paulus, H.E., 1986. FDA Arthritis Advisory Committee meeting: Methotrexate; guidelines for the clinical evaluation of antiinflammatory drugs; DMSO in scleroderma. Arthritis Rheum. 29, 1289-1290; Tugwell, P., Bennett, K., and Gent, M., 1987. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. Ann. Intern. Med. 107, 358-366.]. Since then, rheumatologists have become aware of what Pincus et al. have called "the side effects" of RA comparing the morbidity and mortality caused by RA with that potentially caused by medications used to treat this disease [Pincus, T. and Callahan, L.F., 1993. The "side effects" of rheumatoid arthritis: joint destruction, disability and early mortality. Br. J. Rheumatol. 32, 28-37.]. Thus, during the 1990s the use of MTX for the treatment of RA became generalized [O'Dell, J.R., 1997. Methotrexate use in rheumatoid arthritis. Rheum. Dis. Clin. N Am. 23, 779-796 (a); Bannwarth, B., Vernhes, J., Schaeverbeke, T., and Dehais, J., 1995. The facts about methotrexate in rheumatoid arthritis. Rev. Rhum. 62, 471-473 (b); Bologna, C., Jorgensen, C., and Sany, J., 1997a. Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients. Clin. Exp. Rheumatol. 15, 597-601; Bologna, C., Viu, P. (ABSTRACT TRUNCATED)
9709176 HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. 1998 Apr OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.
10888712 A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment 2000 Jun OBJECTIVE: To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). METHODS: In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. RESULTS: After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. CONCLUSIONS: Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.
total：9168 literature First Prev 5 pages 4647484950 Next 5 pages Last