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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| 11037892 | A cost-effectiveness analysis of treatment options for patients with methotrexate-resistan | 2000 Oct | OBJECTIVE: Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. METHODS: We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. RESULTS: In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. CONCLUSION: Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable. | |
| 10834865 | Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial. On beha | 2000 Jun | OBJECTIVES: To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect. METHODS: Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up. RESULTS: All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies. CONCLUSION: Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity. | |
| 11475244 | [Leflunomide--the first specific disease-modifying drug against rheumatoid arthritis]. | 2001 Feb 7 | Rheumatoid arthritis (RA) is a disabling disorder with chronic inflammation leading to significant disability and pain if not treated early and effectively. Leflunomide is the first drug developed and registered specifically for modifying disease course in RA, and is a good complement to other forms of drug therapy currently in use. In clinical trials, leflunomide has been proven to exert an effect on clinical parameters of RA-inflammation superior to placebo and equal to methotrexate and sulphasalazine, while clinical response evidently begins somewhat earlier than on these other drugs. There appears to be a retarding effect on radiographic progression over 13 months comparable to that of methotrexate and sulphasalazine. The very long elimination half-life as well as side effects including nausea, diarrhea, and elevated liver enzymes (almost as frequent as with methotrexate) hamper its usefulness, and its definitive place in modern RA-therapy remains to be established. | |
| 9415631 | Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pn | 1997 Dec | OBJECTIVE: To determine the clinical features of methotrexate (MTX) pneumonitis in patients treated for rheumatoid arthritis (RA). METHODS: The medical records of 284 patients with RA who had been treated with oral MTX (mean followup 33.2 mo) were reviewed retrospectively. RESULTS: MTX induced interstitial pneumonitis developed in 6 patients (2.1%). The affected patients were significantly older than those without MTX pneumonitis (67.3 +/- 9.8 vs 52.4 +/- 12.6 yrs, respectively; p < 0.005). The cumulative MTX dose ranged from 65 to 580 mg at the time pneumonitis developed. Five of the patients (83%) had preexisting interstitial abnormalities, while only 29 of the 278 patients without MTX pneumonitis (10%) had such abnormalities (p < 0.001). The frequency of adverse effects due to previous treatment with disease modifying antirheumatic drugs (DMARD) was 66.7% in MTX pneumonitis patients and 14.3% in the other 278 patients (p < 0.01). CONCLUSION: Advanced age, preexisting interstitial abnormalities, and previous adverse reactions to DMARD may be associated with MTX pneumonitis. Patients with these characteristics require careful monitoring during MTX therapy. | |
| 11379415 | New disease modifying agents in adult rheumatoid arthritis. | 2001 Mar | In recent years, new disease modifying agents including leflunomide and tumour necrosis factor (TNF) antagonists have been used to treat patients with rheumatoid arthritis (RA). Leflunomide prevents proliferation of activated lymphocytes by inhibiting dihydroorotate dehydrogenase, a critical step in de novo pyrimidine synthesis. Leflunomide has been shown to be as effective as sulfasalazine and methotrexate (MTX) in placebo-controlled trials. It also improves physical function, quality of life measures and retards radiographic progression. TNF antagonists include infliximab and etanercept. Infliximab is a chimeric TNF monoclonal antibody. Repeated infusions of low dose infliximab (1 mg/kg) are ineffective if given alone. Addition of MTX to infliximab has been shown to prolong the duration of clinical response. Etanercept is a human TNF receptor p75 Fc fusion protein. In active RA patients with suboptimal response to MTX, additional clinical benefit was obtained by the addition of infliximab or etanercept to MTX. The main side effect of etanercept is injection site reaction. However, the long-term effect of TNF antagonists in the development of infection, malignancy and autoimmune disease remains unknown. | |
| 11508581 | Influence of longterm therapy with methotrexate and low dose corticosteroids on type 1 and | 2001 Aug | OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominance of type I cytokine [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] production. In this prospective study, we evaluated the influence of longterm therapy with methotrexate (MTX) in combination with low dose corticosteroids on the type 1/type 2 cytokine balance in RA. METHODS: Peripheral blood mononuclear cells were isolated from 10 controls and 20 patients with RA before therapy and after 12 mo of therapy with MTX in combination with low dose corticosteroids. Using flow cytometry, the intracellular production of IL-2, IFN-gamma, and IL-4 was measured in CD4+ and CD8+ T lymphocytes. RESULTS: Compared with healthy controls, patients with RA before therapy showed an increased percentage of IL-2 positive CD4+ and CD8+ T cells (p = 0.002, p = 0.01, respectively). An increased percentage of IFN-gamma positive CD8+ T cells was found (p = 0.0006) compared with the control group. After 12 months of therapy, a significantly decreased percentage of IL-2 positive CD4+ T cells and IFN-gamma positive CD4+ and CD8+ T lymphocytes was observed (p = 0.0003, p = 0.0007, p = 0.001). The percentage of IL-4/IFN-gamma positive CD4+ and CD8+ T cells was significantly higher after 12 months of therapy (p = 0.01, p = 0.02). There was a positive correlation between the percentage of IFN-gamma positive CD4+ T cells and disease activity variables (Ritchie Index and number of swollen joints) in RA patients before therapy (r = 0.6, p = 0.04 and r = 0.4, p = 0.05). CONCLUSION: Longterm therapy with MTX in combination with low dose corticosteroids for RA influenced the predominance of type 1 cytokines toward normalization of the cytokine balance in both CD4+ and CD8+ T lymphocytes. | |
| 9825744 | A 36 month comparative trial of methotrexate and gold sodium thiomalate in the treatment o | 1998 Oct | OBJECTIVE: To compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with active early erosive rheumatoid arthritis (RA) during 3 yr. METHODS: A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections of either 15 mg MTX or 50 mg GSTM for 1 yr in a double-blind fashion. Thereafter, the study was continued as an open prospective trial for an additional 2 yr with the same dose of MTX and half of the GSTM dose. Clinical and laboratory evaluations were carried out at baseline and at months 6, 12, 18, 24 and 36 in all patients, including withdrawals. RESULTS: An intention-to-treat analysis revealed inactivation ['clinical remission': no swollen/tender joints, erythrocyte sedimentation rate (ESR) of < 20 mm/h in males and < 30 mm in females, no corticosteroids within the last 4 weeks] in 33.3% of MTX patients and 37.9% of GSTM patients. The mean time to inactivation was insignificantly shorter with GSTM (MTX: 12.1 months; GSTM: 9.1 months; P = 0.06). At least marked improvement (> 50% reduction of the number of swollen/tender joints and of the ESR) was found in 78.2% (MTX) and 87.4% (GSTM). Withdrawal from the study due to toxicity was recorded in 16.1% of MTX and 52.9% of GSTM patients after a mean time of 30.6 and 6.1 months, respectively (P = 0.0001). In MTX and GSTM non-completers, inactivation was recorded in 24.2 and 54.7% of all patients. Among completers (54 and 34 patients, respectively), significant improvement compared to baseline was noted in all seven clinical variables (morning stiffness, overall joint pain, count of tender/swollen joints, Lansbury articular score, functional score and grip strength), ESR and C-reactive protein without significant intergroup differences. The steroid-sparing effect appeared more pronounced with GSTM. CONCLUSION: Over 36 months, treatment with MTX or GSTM induces inactivation ('clinical remission') of early and erosive RA in about one-third and at least marked improvement in four-fifths of patients (intention-to-treat analysis). Patients withdrawn from MTX or GSTM due to toxicity develop a clinical remission from the disease; this occurred more often with GSTM. Tolerability is significantly better with MTX. | |
| 11641084 | [Methotrexate, liver and rheumatoid arthritis in tropical areas]. | 2001 Jul | Rheumatoid arthritis (RA) is a common disease in tropical areas. Methotrexate which has become the main first-line treatment in western countries is increasingly used in tropics. Well documented liver toxicity of methotrexate led the American College of Rheumatology to provide guidelines about monitoring patients. In endemic areas of hepatitis B and C methotrexate may interfere with the natural history of these infections and exarcerbate liver damage, on the other hand, RA causes extra-articular manifestations which are rare and exceptionnally serious in the liver. The most important hepatic disorders associated with RA are: intrahepatic portal hypertension without cirrhosis, amyloidosis, drug hepato-toxicity and viral interferences. - Intrahepatic portal hypertension Several cases of portal hypertension without cirrhosis have been reported. Most cases were related to Nodural Regenerative Hyperplasia (NRH) which is made of diffuse nodules of hepatocytes without fibrosis. The pathogenesis of this entity is unknown. Distal vascular changes and abnormal perfusion of liver are mentioned. Presentation is cholestasis in one third of cases. Portal hypertension has no particularity and may cause esophageal variceal bleeding. NRH is closely associateed with Felty's syndrome. - Amyloidosis Hepatic amyloidosis is a classical complication of RA even rare. It is a secondary amyloidosis of AA type. Hepatic injury is generally silent and renal symptoms are dominant. - Drug hepatotoxicity Several medications used in the management of RA are potentially hepatotoxic : salicylates, nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, gold, sulfasalazine and methotrexate above all. Methotrexate hepatotoxicity is well documented in carcinology with high doses but also in psoriasis patients treated with low doses. Hepatic damage related to methotrexate includes elevation of aminotransferases, portal fibrosis and cirrhosis. But data on methotrexate toxicity show small risk of serious liver disease in RA patients. Long duration of therapy and age (> 60 years) have been found to be independent risk factors for the development of hepatic disease. Other identified risk factors are alcohol intake, diabetes, obesity and prior history of hepatitis B or C. The American College of Rheumatology has published guidelines about monitoring patients for liver toxicity. Hepatic tests and Hepatitis B and C serologic studies are recommended before starting treatment with methotrexate. Liver biopsy is only recommended in case of alcoholism, prolonged abnormalities of aminotransferases and chronic hepatitis B or C infection. - Methotrexate and hepatitis B or C infection These infections are endemic in tropical areas. Chronic hepatitis B or C is a contra indication for methotrexate therapy, due to the immuno-suppressive effect of the drug. Positive ELISA tests to C virus must be confirmed with RIBA tests to avoïd false positive tests which have been reported in Africa. The "healthy" HBs Ag carrier state is not in theory a contra indication for methotrexate therapy but the risk of hepatitis B reactivation needs a close monitoring. The biological tests required for are sophisticated and quite impossible in routine practice in tropical areas. So HBs Ag carrier state is usually incompatible with methotrexate treatment. Studies would be useful to prove that in endemic areas of viral hepatitis B and C as in western countries, methotrexate is enough safe to become the main first-line treatment of rheumatoid arthritis. | |
| 9361164 | The use of folates concomitantly with low-dose pulse methotrexate. | 1997 Nov | Toxicities related to low-dose weekly methotrexate are largely due to its antifolate properties. Preexisting folate deficiency is associated with methotrexate toxicity in some patients. At the onset of methotrexate therapy and throughout therapy, the physician should be vigilant regarding one or more nutrient deficiencies. A multivitamin and, where appropriate, specific daily folic acid supplements should be employed. The only regimen known presently (through controlled trials) to treat side effects is the low-dose folinic acid (leucovorin) protocol outlined herein. Folic acid may be helpful to treat mild gastrointestinal symptoms. Folinic acid supplementation should be considered prophylactically in those requiring methotrexate who are at increased risk of hepatic disease. Other possible factors besides methotrexate should always be considered with the onset of new patient complaints or laboratory abnormalities. Claims that folic acid therapy is safer and more convenient than folinic acid seem unwarranted when one reviews the literature carefully. Cost differences between folic acid supplementation and folinic acid supplementation have been exaggerated. | |
| 11075396 | [Value of anti-TNF-alpha molecules in inflammatory and infectious diseases]. | 2000 Oct | INTRODUCTION: The pathophysiological interest of tumor necrosis factor-alpha (TNF-alpha) has been recently reported in inflammatory and infectious diseases. Thus, TNF-alpha blockade has become a new field of therapeutical research. CURRENT KNOWLEDGE AND KEY POINTS: Several biological agents specifically directed against TNF-alpha are available: anti-TNF-alpha monoclonal antibodies on the one hand--either mainly murine sequence (cA2), partially humanized (CDP 571) or fully human (D2E7)--and TNF-alpha soluble receptors on the other hand (lenercept or etanercept). The first clinical studies reveal interesting results. In rheumatoid arthritis (cA2, etanercept), these molecules may be used either alone or in synergistic combination with methotrexate. They produce a significant response compared to placebo or methotrexate alone, without loss of efficacy in medium-term treatment. In Crohn's disease (cA2 CDP571), they reduce significantly the activity of the disease, compared to placebo, and cA2 makes it possible to accelerate closure of the fistulas. The studies of severe sepsis did not reveal a significant efficacy, however, and only one study has been published on malignant disease, with a possible interesting effect. Even if these medications are usually well tolerated, the frequency of infections is slightly increased. The development of anti-DNA antibodies has also been reported, but drug-induced lupus is highly unusual. FUTURE PROSPECTS AND PROJECTS: Further studies will define the place of anti-TNF-alpha biological agents among the other available treatments of rheumatoid arthritis and Crohn's disease. Because of their high cost, these drugs will probably be limited to patients with active inflammatory disease despite more conventional treatments. | |
| 9972962 | Safety of self-injection of gold and methotrexate. | 1999 Feb | OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient. | |
| 11426031 | WHO Collaborating Centre consensus meeting on anti-cytokine therapy in rheumatoid arthriti | 2001 Jun | Severe adult rheumatoid arthritis is a cause of progressive disability and increased mortality across Europe. A cure for the disease remains elusive, but control of symptoms and maintenance of individual independence is possible. Anti-cytokine therapies offer a new approach to disease management. They are effective after the failure of full doses of methotrexate, and are at least as effective as methotrexate in retarding the progression of radiological changes. Until more is known about the long-term safety and efficacy of these drugs they should be reserved for patients with severe disease who are progressing despite adequate doses of methotrexate or other disease-modifying anti-rheumatic drugs. They should be continued until therapeutic failure or intolerance. A comprehensive health economic evaluation is needed to optimally direct the use of these drugs. This should be undertaken when long-term safety and efficacy studies are completed. | |
| 11302876 | Treatment with cyclosporin switching to hydroxychloroquine in patients with rheumatoid art | 2001 May | OBJECTIVE: To investigate the therapeutic benefit of cyclosporin A (CSA) switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS: Thirty four patients with RA who displayed residual inflammation and disability despite partial responses to prior maximal tolerated doses of methotrexate, were included. All were treated with a staged approach using CSA for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to maintain the improvement. Seven ACR core set measures were evaluated every four to eight weeks. RESULTS: During a 40 week open trial, 27/34 patients completed the study. CSA treatment significantly reduced the tender joints score, swollen joints score, visual analogue pain scale, patient's or doctor's global assessment, patient's self assessed disability, and C reactive protein. Compared with the time of entry into the trial, patients who switched from CSA to HCQ still possessed significantly lower levels of most variables, determined at 28, 32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%) patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained improved at 16 weeks after the change to HCQ. Frequent side effects, such as hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA treatment, but most of these disappeared after switching to HCQ. The mean levels of blood pressure and serum creatinine were significantly increased during CSA treatment, but returned to normal after changing to HCQ. CONCLUSIONS: The data suggest that CSA switching to HCQ treatment may be an effective strategy for patients with RA partially responding to methotrexate, particularly those with toxicity due to CSA. | |
| 11249494 | Tumour necrosis factor-alpha blockade: a new era for effective management of rheumatoid ar | 2000 Jul | Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF-alpha in RA derives from extensive work in the laboratory, showing the importance of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of principle has now been firmly established in clinical trials where TNF-alpha inhibitors have been shown to decrease the signs and symptoms of joint inflammation and slow radiological progression of joint damage. Presently, the two TNF-alpha inhibitors available for use in RA are etanercept and infliximab. Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody, which also binds with high affinity to soluble TNF-alpha. Etanercept and infliximab will be rapidly incorporated into current treatment paradigms, which call for early and intensive treatment of RA using disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of these biologics is their high costs. Some patients with limited financial means may be denied access to these effective anti-inflammatory agents. Moreover, long-term experience with TNF-alpha inhibitor therapy has been limited and concerns linger about the possibility that etanercept and infliximab may cause unforeseen side effects or increase the risk for opportunistic infection. Despite these caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA and will likely spawn new indications for anti-TNF-alpha therapy and the development of novel therapeutic compounds with similar biological activity. | |
| 10833963 | [Felty's syndrome]. | 2000 Mar 30 | BACKGROUND: Felty's syndrome is a complication of rheumatoid arthritis whereby patients develop neutropenia of varying severity and splenomegaly. The major sources of morbidity and mortality are recurrent local and systemic infections, although some patients remain asymptomatic. MATERIAL AND METHODS: In this paper two patients with Felty's syndrome are presented. RESULTS: One patient had recurrent infections. Clinical manifestations, laboratory features and different modalities of treatment are reviewed. INTERPRETATION: Splenectomy has long been standard therapy, but disease modifying antirheumatic drugs (such as gold salts and methotrexate) and colony stimulating factors should also be considered in Felty's neutropenia complicated with infections. | |
| 10408141 | Tumor necrosis factor inhibitors for rheumatoid arthritis. | 1999 | Tumor necrosis factor antagonists such as infliximab and etanercept represent a new and powerful approach to managing RA. In studies published to date, TNF antagonists appear to be safe and effective agents for short-term therapeutic use in RA. Defining when in the course of RA to use TNF antagonists and determining the effectiveness of combinations of these biologic agents with DMARDs or other cytokine antagonists are areas of current and future studies. Other cytokine antagonists that may be promising subjects for further study are IL-1 antagonists. Like TNF, IL-1 is a member of the inflammatory cascade, but may play a different role in the development of inflammatory arthritis. In animal models, inhibition of TNF suppressed the inflammatory response while IL-1 antagonism prevented joint destruction (2). These results imply that combination therapy providing inhibition of both IL-1 and TNF might be an effective treatment in humans with RA, but clinical trials in humans have not yet been performed. Studies are underway in people with early RA to determine if the new TNF inhibitors are more effective or safer than currently available therapies, such as methotrexate. Other agents that inhibit TNF activity are also being tested at this time in people with RA. | |
| 10334255 | Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: | 1999 May 8 | BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis. | |
| 9214432 | Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes: | 1997 Jul | OBJECTIVE: To determine why methotrexate (MTX) exacerbates rheumatoid nodules in some patients, despite the effective suppression of synovial inflammation. METHODS: Phorbol myristate acetate (PMA)-induced differentiation of monocytes into multinucleated giant cells was used as an in vitro model to study the effects of adenosine on nodulosis. RESULTS: MTX at 200-2,000 nM or the adenosine A1 agonist N5-cyclopentyl adenosine (CPA) (10(-12) to 10(-9) M) or the A2 antagonist 3,7-dimethyl-1-propargylxanthine markedly enhanced giant cell formation, whereas the adenosine A1 antagonist 8-cyclopentyl-dipropylxanthine completely reversed these effects. PMA, CPA, and MTX induced adenosine release by cultured monocytes at concentrations consistent with those associated with predominantly A1 effects. Furthermore, surface expression of A1 receptors was found to remain unchanged on the differentiating cells throughout the culture period. CONCLUSION: Agents that inhibit adenosine A1 receptors might be useful in the treatment of MTX-induced rheumatoid nodulosis, while still potentiating the A2-mediated antiinflammatory effects of MTX on synovitis. | |
| 11464603 | [Neutropenic enteropathy associated with autoimmune diseases. A more aggressive presentati | 2000 Jul | BACKGROUND: There is just one case report dealing with neutropenic enteropathy associated with autoimmune diseases. METHOD: An autopsy analysis of neutropenic enteropathy in autoimmune and hematologic diseases was carried on. Gross findings and slides were reviewed. A blind analysis is of the mucosal lesions in small and large intestine as well as of the clinical course was made. RESULTS: Seventeen cases of neutropenic enteropathy were found a once period of 13 years (1,068 autopsies). Fourteen cases were seen in patients with hematologic diseases and three in patients with autoimmune diseases. Acute symptoms had a 6-day evolution and were characterized by abdominal pain, diarrhea, ascitis, and fever in autoimmune diseases. Extension of colonic damage was 58 and 13% in small bowel. Cases associated with hematologic diseases had longer clinical course with fever abdominal pain and colonic lesions in 21% of the surface and small bowel lesions in 6% of the mucosa. No acute inflammatory infiltrate around the necrotic zones was observed in either group Azathioprine, steroids, methotrexate, and alkylating agents were associated to neutropenia. CONCLUSIONS: Clinical evolution and morphologic findings were more severe in neutropenic enteropathy associated with autoimmune diseases than in patients with hematologic diseases. | |
| 11357167 | The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoi | 2001 Apr | BACKGROUND: Interleukin (IL)-1 has been associated with joint inflammation and damage in rheumatoid arthritis (RA). Endogenous IL-1 receptor antagonist (IL-1Ra) may inhibit IL-1-mediated effects by binding to the IL-1 receptors. OBJECTIVES: These studies were conducted to determine the efficacy and safety of human recombinant IL-1 receptor antagonist (IL-1ra) in blunting the effects of IL-1 in patients with RA. METHODS: Three randomized clinical trials have been completed. First, in a 24-week, double-blind, placebo-controlled study of 472 patients with severe RA, patients were randomly placed into 4 groups: placebo or IL-1ra at 30, 75, or 150 mg/d. In a second study, 309 patients from the placebo-controlled trial enrolled in a 24-week extension study. Patients who had been receiving placebo were randomized into 1 of the 3 treatment groups. Those receiving treatment continued to receive their previous dosages. Finally, in a second double-blind, placebo-controlled study, 419 patients with RA receiving methotrexate at 12.5 to 25 mg/wk for at least 6 months were randomly placed into 1 of 6 groups: placebo or IL-1ra at 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg/d. RESULTS: In the first study, the primary therapeutic endpoint-an American College of Rheumatology 20% response (ACR20)-was reached by 27% of the placebo group, compared with 43% of the IL-1ra 150-mg/d group. Individual clinical responses, as well as the arrest of joint damage, were also superior in treated patients. In the second trial, 52% of the randomized patients achieved an ACR20. This was maximal (71%) in those receiving the highest treatment dosage. Of patients continuing with the same dosage, 49% maintained an ACR20 at 48 weeks. Radiologic evaluation showed that the reduced rate of cartilage degradation observed in treated patients during the first 24 weeks was maintained, and the rate of joint erosion was slowed even more significantly in the second phase of the study. In the third study, significantly more patients receiving IL-1ra at 1.0 (46%, P =.001) or 2.0 (38%, P =.007) mg/kg/d achieved an ACR20 at week 12 than those receiving placebo (19%). Similar responses were noted at week 24. IL-1ra was generally well tolerated, with injection site reaction the most frequent adverse event. No serious adverse events attributable to IL-1ra treatment were observed. CONCLUSIONS: These studies suggest an important role for IL-1ra as a novel therapeutic agent in the treatment of RA. |