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ID PMID Title PublicationDate abstract
14632315 Plasma from rheumatoid patients taking low dose methotrexate enhances platelet aggregation 2002 Methotrexate (MTX) in low doses is commonly used to treat rheumatoid arthritis (RA). At least 36 deaths have been attributed to bone marrow cytotoxicity associated with low dose MTX. The goal was to determine if plasma from arthritis patients taking low dose MTX induces platelet aggregation in platelet rich plasma from healthy volunteers. Plasma from patients on MTX alone caused a 3-fold increase in aggregation vs plasma from controls (P<0.05). Plasma from patients not taking MTX or taking MTX with diclofenac caused aggregation to a lesser extent. Diclofenac, along with several others NSAIDs and cyclooxygenase inhibitors, depressed aggregation produced by arachidonic acid in platelet rich plasma from healthy volunteers. A precise mechanism for amplification of aggregation by MTX plasma and its relationship to MTX toxicity remains unknown. However, a serum factor may be produced by MTX that modulates the activity of cyclooxygenase, thereby influencing aggregation.
12492247 Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis 2002 OBJECTIVE: We study liver damage in forty-two patients with rheumatoid arthritis (RA) using light (LM) and electron microscopy (EM) and assess histological changes after four years of treatment with methotrexate (MTX). PATIENTS AND METHODS: liver biopsies (LB) were taken before and after four years of treatment. Patients received weekly doses of between 7.5-15 mg of MTX. RESULTS: Fourteen per cent of the baseline LB presented mild perisinusoidal fibrosis (Roenigk IIIA) and the rest a lower Roenigk grade; EM identified an increase in collagen fibers in the Disse spaces in 50% of baseline LB. Neither microscopy technique revealed histological progression in any of the sequential LB. Variables that correlated with histological abnormalities were patient's age, length of evolution of the disease, alcohol consumption and biochemical data (gammaglutamate transferase and albumin); the cumulative dose of MTX was not correlated with worse histological findings. Correlation between the two microscopy techniques was good, though EM was more sensitive than LM for the detection of fibrosis. CONCLUSIONS: RA patients present with liver damage before treatment with MTX. The alterations are mild. At low doses MTX treatment is safe. In addition to the recommendations of the American College of Rheumatology, other factors associated with liver impairment are patient's age and length of evolution of the RA.
14513112 [Rheumatoid arthritis and atherosclerosis]. 2003 Evidence continue to accumulate indicating that patients with rheumatoid arthritis (RA) present an increased risk of cardiovascular disease (and death). The risk factors for coronary artery disease (CAD) in RA are not fully understood. However, a number of possible factors have been described, but more than one may be efficient, such as homocysteine, presence of antiphospholipid antibodies, altered serum levels of selected lipoproteins, and all together may have implications for the atherogenesis observed in these patients. Other factors that may facilitate this process, include corticosteroid use, methotrexate therapy and hormonal factors. However, the relative importance of these specific risk factors for the atherogenesis in this disease is poorly known. Recent findings indicate that cardiac death is increased in RA patients when compared with subjects without arthritis and that generally, the inflammatory process may contribute to atherosclerosis. In addition, other studies indicate that serum concentration of pro-inflammatory cytokines are found elevated at baseline, among patients at risk for future coronary occlusion.
16136957 [Effect of bizhongxiao decotion on TNF-alpha and interleukin-1beta in plasma of rats with 2004 Jun OBJECTIVE: To observe the influence of bizhongxiao decotion (BZXD) on the plasma TNF-alpha and IL-1beta in rats with C II-induced arthritis (CIA) and to explore the mechanism of BZXD in the treatment of rheumatoid arthritis. METHODS: We divided 75 rats into 4 groups randomly. The rat experimented arthritis model was established by subcutaneous injection with collagen II. The plasma TNF-alpha and IL-1beta levels were detected with the radio-immunity assay at different time spots. RESULTS: The incidence of arthritis in the rats immunized with C II was approximately 88%. The plasma TNF-alpha and IL-1beta levels of the model group, BZXD group and methotrexate (MTX) group were notably higher than those of the normal group (P < 0.05). The plasma TNF-alpha and IL-1beta levels of the model group were higher than those of the MTX control group and BZXD treatment group at different time spots (P < 0. 01). The plasma TNF-alpha and IL-1beta levels rose step by step, but those of the BZXD group and MTX group decreased gradually. Moreover, the plasma TNF-alpha and IL-1beta levels of the rats of BZXD group were lower than those of the MTX group (P < 0. 05). CONCLUSION: TNF-alpha and IL-1beta play a very important role in the formation and development of rheumatoid arthritis. Both BZXD and MTX can notably decrease the plasma TNF-alpha and IL-1beta levels, but the effect of BZXD is better than that of MTX.
15301246 Renal function in rheumatoid arthritis patients treated with methotrexate and infliximab. 2004 Jul OBJECTIVE: This study was aimed at monitoring the early and late effects of infliximab on renal proximal function in RA patients treated with methotrexate. N-acetyl-3-D-glucosaminidase (NAG) activity in urine served as an indicator of proximal tubular damage METHODS: NAG activity was estimated in 21 patients during the course of treatment with infliximab and methotrexate. In every patient NAG-enzymuria was estimated directly before and 60 min after infliximab infusions and 62 weeks after starting the therapy. RESULTS: The total of mean NAG activities observed before each infusion of infliximab was significantly lower (p < 0.02) than NAG-enzymuria before the start of infliximab treatment (7.4 UI/g vs 11.8 UI/g). The proportion of patients in whom NAG activity rose by more than 50% during treatment ranged from 5.3% to 25%. Administration of infliximab did not significantly change the mean serum creatinine levels or creatinine clearance. No significant differences were observed in the mean values of NAG values before and 60 min after infliximab infusion. Patients who demonstrated elevated NAG activities during the course of the whole treatment demonstrated significantly more pronounced NAG enzymuria before treatment and one hour after the first infusion (p < 0.0005), as well as higher RA activity (p < 0.05). There was no observed influence of NSAIDs or prednisone on the frequency of elevated NAG activities. Raised creatinine concentrations (> 1.3 mg/dL) were noted before and during the course of infliximab treatment in 3 patients. In 16 patients abdominal fat aspiration biopsy was performed and in 3 the presence of amyloid deposits was demonstrated. In these patients NAG activity exceeded twice the upper normal limit. CONCLUSION: The introduction of infliximab during methotrexate therapy demonstrated no early or delayed nephrotoxicity of the drug in patients with rheumatoid arthritis.
15208869 [Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on fu 2004 Mar Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.
15570637 Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated w 2004 Dec OBJECTIVE: To investigate the effect of methotrexate (MTX) treatment of rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of low dose folic acid on toxicity, efficacy, and folate status. METHODS: A 52-week prospective study of 81 patients with RA treated with MTX and self-administered low dose folic acid; 38 patients were included prior to MTX therapy, 33 patients continued established MTX therapy, and 10 patients were excluded. Drug efficacy and side effects were monitored with biochemical and clinical indicators. RESULTS: MTX treatment resulted in decreased concentrations of red blood cell (RBC) folate and a rise in plasma homocysteine. Intracellular concentrations of MTX were inversely correlated to RBC folate levels after treatment for a longer period (mean 41 months). Supplement with low dose folic acid prevented or diminished the influence of MTX on folate status and had a protective effect on MTX induced liver toxicity without changing the efficacy of MTX. CONCLUSION: MTX interferes with folate and homocysteine metabolism, and the intracellular concentration of MTX may play a role. Our results indicate low dose folic acid supplementation has a beneficial effect on MTX toxicity.
14872477 Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been un 2004 Feb OBJECTIVE: To examine whether dose escalation of intramuscular (IM) methotrexate (MTX) up to 45 mg/week improves disease control in patients who have active rheumatoid arthritis (RA) despite receiving conventional doses (15 mg/week) of IM MTX, and to obtain preliminary data on patient tolerability and adverse effects of higher doses of IM MTX. METHODS: Patients >18 years of age who had active RA, defined as a European League Against Rheumatism (EULAR) Disease Activity Score in 28 joints (DAS28) of >3.2, and who had received 15-20 mg/week of oral MTX for at least 2 months were switched (week 0) to 15 mg/week of IM MTX for 6 weeks. Patients whose DAS28 remained >3.2 at both week 4 and week 6 were randomized, in a double-blind manner, either to continue to receive 15 mg/week IM MTX with monthly placebo escalation or to receive escalating doses of IM MTX monthly up to 45 mg/week. The dose of MTX or placebo was escalated every 4 weeks if the DAS28 was >2.5. Safety assessments and determination of the DAS28 were performed every 2 weeks and monthly, respectively. Disease activity parameters from the American College of Rheumatology (ACR) core disease activity set and health status as recorded on the Medical Outcomes Study Short-Form 12 were determined at baseline (week 0) and final assessment (week 22). The primary outcome was the percentage of patients in each group achieving a target DAS28 of <3.2. Secondary outcomes comprised the percentage of patients whose DAS28 improved by >1.2, the percentage of patients achieving a 20% improvement in the ACR core disease activity measures (ACR20), and the percentage of patients achieving a good response, a moderate response, or no response in accordance with the EULAR response criteria. RESULTS: Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean +/- SD DAS28 was 5.6 +/- 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups -15% to +15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups -18% to +18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group. CONCLUSION: Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15 mg/week IM MTX, increasing the dose up to 45 mg/week does not improve disease control. Higher doses of IM MTX were generally well tolerated and not associated with an increase in serious adverse reactions to the drug.
12730518 Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up 2003 Sep OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.
15195775 Rheumatoid arthritis: more aggressive approach improves outlook. 2004 May As recently as 10 years ago, many patients with rheumatoid arthritis would receive only a nonsteroidal anti-inflammatory drug and low-dose corticosteroids until damage to their joints was documented. Now, despite risks of toxicity and adverse effects, a disease-modifying antirheumatic drug such as methotrexate is given as early as possible to retard disease progression and help prevent new erosions. Other agents can be added to or used in place of methotrexate, such as a biologic response modifier that regulates the proinflammatory cytokine tumor necrosis factor-alpha.
15134615 Infectious and healing complications after elective orthopaedic foot and ankle surgery dur 2004 May BACKGROUND: Biologic response modifiers are assuming a larger role in the management of patients with rheumatoid arthritis. The tumor necrosis factor-alpha (TNF-alpha) inhibitors etanercept and infliximab improve patient symptoms and function. However, these agents have been associated with a risk for healing and infectious complications due to systemic blockade of TNF-alpha, a ubiquitous mediator required in the normal inflammatory response in tissue healing and infection surveillance. This study analyzed the risk of healing/infectious complications in patients undergoing elective foot and ankle surgery while being treated with TNF-alpha inhibitors etanercept and infliximab. METHODS: Patients with rheumatoid arthritis undergoing elective foot and ankle surgery over a 12-month period were prospectively followed for the development of complications in the postoperative period. All patients continued their antirheumatic medication schedule unaltered in the perioperative period. Data collected included sex, age, all medications used to treat rheumatoid arthritis, smoking history, and number of orthopaedic foot and ankle procedures performed. Patients were then stratified into two groups based on the use of immunomodulation via TNF-alpha inhibition (group 1) versus patients who did not receive TNF-alpha inhibition therapy (group 2). Groups 1 and 2 were followed and compared for the development of infectious/healing complications. RESULTS: Thirty-one patients were enrolled in the study. Group 1 (n = 16) and group 2 (n = 15) patients were comparable for sex distribution, number of orthopaedic procedures performed, and use of steroids, methotrexate, leflunamide, and nonsteroidal anti-inflammatory drugs. Group 1 contained six times the number of smokers in group 2. At mean follow-up of 10.6 months (group 1) and 9.7 months (group 2), healing or infectious complications were similar in both groups. However, when total complications (healing + infection) were analyzed, group 1 (TNF-alpha inhibition, "higher risk") patients demonstrated a lower complication rate (p =.033). CONCLUSIONS: The data suggest that in patients with rheumatoid arthritis undergoing elective foot and ankle surgery, the use of TNF-alpha inhibition agents may be safely undertaken in the perioperative period without increasing the risk of healing or infectious complications.
15305245 The use of methotrexate in rheumatoid arthritis. 2004 Aug OBJECTIVE: To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. RESULTS: MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. CONCLUSIONS: MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.
12928941 [Interleukin-1 receptor antagonist anakinra (Kineret) for treatment of rheumatic arthritis 2003 Aug New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation. Proinflammatory cytokines like IL-1 beta and TNFalpha play a crucial role in induction and maintenance of synovitis, pannus formation and bone and cartilage destruction. Within a few years, these morphological changes may lead to joint destruction and consecutively to functional impairment. Since April 2002 a recombinant human interleukin-1 receptor antagonist (Anakinra) is available in Germany for treatment of patients with rheumatoid arthritis. Anakinra (Kineret(R)) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the German Rheumatology Society for the use of biologicals in treatment of patients with rheumatoid arthritis. The approval of anakinra as a new therapeutic is based on data obtained in large multicenter, placebo-controlled, and randomised trials in comparison to placebo. Treatment of Anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 (or more) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions. Anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70% of patients usually after 10-12 days of treatment and that are mostly mild to moderate and self-limiting. Patients with previous pneumonia or other risk factors for pulmonary infections such as chronic obstructive lung disease seem to show a slightly increased risk of developing infectious complications of the bronchopulmonary system while being on anakinra and should be monitored appropriately. Combining IL-1ra treatment with the use of anti-TNF agents showed an increased risk of infectious complications in clinical studies and is not recommended at present. Studies are currently assessing the use of anakinra for treatment of other rheumatic diseases like psoriatic arthritis, juvenile arthritis or spondylarthropathy.
14969078 Role of infliximab in the treatment of early rheumatoid arthritis. 2003 Sep Data has been generated that infliximab may be more effective when initiated earlier in the course of disease. A subset analysis of the Attract trial has demonstrated better efficacy of infliximab in reducing joint damage in an early rheumatoid arthritis (RA) population. Recently a randomized double-blind controlled trial revealed that infliximab in combination with methotrexate (MTX) in an early RA population improved signs and symptoms as well as inhibition in radiographic progression compared with patients receiving infliximab or MTX alone. The possibility of withdrawing infliximab after induction of remission with a combination of infliximab and MTX has been shown in a small pilot trial. Taken together, the results support the early use of infliximab in the treatment of patients with moderate to severe disease.
15338488 Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combine 2004 Sep OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.
15290731 Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus establi 2004 Aug OBJECTIVE: To compare etanercept-induced improvement in disability of patients with recent onset of rheumatoid arthritis (RA) to that of patients with established RA. METHODS: Health Assessment Questionnaire (HAQ) scores were collected over 3 years in 2 groups of patients with RA who were treated with etanercept. The first group consisted of 207 patients with recent onset RA (mean duration of 1 year) who had not previously received methotrexate, and the second group consisted of 464 patients with established RA (mean duration of 12 years) who had failed one or more disease-modifying antirheumatic drugs. RESULTS: Baseline demographics and disease characteristics were similar in the 2 groups, except for HAQ scores and C-reactive protein levels, which were higher in the established RA group. Patients in both groups showed rapid and sustained clinical responses with etanercept therapy, but patients with recent onset RA showed significantly greater improvement in HAQ scores compared with patients with established RA. The difference in magnitude of HAQ score improvement between groups was observed as early as week 2 after initiation of etanercept and persisted throughout the 3-year time frame. At year 3, significantly more patients with recent onset RA had a HAQ score of zero (26%) versus those with established RA (14%, p = 0.0095). CONCLUSION: Although etanercept therapy significantly improved disability scores in both groups, patients with recent onset of RA showed greater benefit in HAQ scores than patients with established RA. These results support prompt treatment of RA at an early stage of disease to minimize patient disability.
15212592 Single nucleotide polymorphism profiling across the methotrexate pathway in normal subject 2004 Jul Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug in rheumatoid arthritis (RA). Polymorphisms occur in several genes encoding key enzymes in the folic acid pathway, which is influenced by MTX, but have not been evaluated in patients with RA. The effect of race on allele frequency has also not been evaluated. In this study, the allele frequencies of polymorphisms in six key enzymes in the MTX-folate pathway in patients with RA and healthy controls, including several common racial groups were studied. European- and African-American patients with RA and European and African healthy controls were genotyped for 22 genetic loci in six genes in the MTX cellular pathway. Differences in genotype distributions between the different racial groups were evaluated using chi(2) tests. Allele frequencies were significantly different (p < 0.001) for eight single nucleotide polymorphisms between the European and African controls. The allele frequencies of two polymorphisms showed significant differences (p < 0.001) between the African- and European-American patients with RA. Thus, racial differences exist between the allele frequencies of several polymorphisms in enzymes in the MTX-folate pathway in patients with RA and healthy controls. Whether such differences contribute to a differential response to MTX in patients with RA deserves to be investigated.
11950005 Open label study to assess infliximab safety and timing of onset of clinical benefit among 2002 Apr OBJECTIVE: To assess the timing of onset of clinical benefit following the initial infusion of infliximab and to obtain additional safety experience of infliximab when given in an office setting to patients with rheumatoid arthritis (RA). In addition, the safety of reducing the infusion time from 2 hours to 1 hour was evaluated. METHODS: Patients (n = 553) with active RA despite receiving methotrexate (MTX) were treated with infliximab 3 mg/kg given over 2 h at baseline (Week 0), and Weeks 2, 6, and 14 in this multicenter open-label trial. Patients continued to receive a stable dose of MTX (> or = 7.5 mg/wk). At selected sites, patients tolerating the first 4 infusions were eligible to receive 2 additional infusions at twice the usual infusion rate (given over 1 h). Patients returned for efficacy assessments at 48 h following the initial infusion and several times throughout study participation. RESULTS: By 48 h following the first infusion, significant (p < 0.001) improvements were observed in duration of morning stiffness (34% mean improvement), physician's global disease assessment scores (30%), patient's global disease assessment scores (25%), and patient's pain assessment scores (30%). By Week 16, 52 to 63% mean improvements in these efficacy variables were observed (p < 0.001), the significant improvement was maintained through the end of study participation in the subset of patients who received the additional 1 h infliximab infusions. Through 16 weeks, 10% (54/553) of patients reported an adverse event associated with at least 1 of the 4 infusion procedures; the majority were mild and transient in nature. In the subset of 197 patients who received 2 additional infusions over 1 h, no increase in the frequency or severity of infusion-related adverse events was observed compared to the 2 h infusion. CONCLUSION: Infliximab administered to patients with RA in an outpatient setting resulted in significant clinical improvement within 48 h that was sustained with additional infusions. Approximately 10% of patients experienced an infusion reaction, highlighting the need for direct supervision over patient treatment. Patients who tolerated infliximab infusions given over 2 h also tolerated a 1 h infusion.
12003373 Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. 2002 Apr Leflunomide, a new oral immunomodulatory agent, is effective for the treatment of rheumatoid arthritis. Its mechanism of action in suppressing inflammation is based in its inhibition of dihydroorotate dehydrogenase, an enzyme responsible for de novo synthesis of pyrimidine containing ribonucleotides. It is the first disease-modifying antirheumatic drug approved for treatment of rheumatoid arthritis with an indication for retardation of joint damage by radiography. Side effects are generally mild and include diarrhea, rashes, reversible alopecia, and elevation of hepatic transaminases. Despite the concern about hepatotoxicity, combination use with methotrexate in treating patients with rheumatoid arthritis has been shown to be safe. Other autoimmune diseases in which leflunomide has been used successfully include Felty syndrome, vasculitis, Sjogren syndrome, Wegener granulomatosis, and bullous pemphigoid.
15053456 Ten-year radiographic outcome in patients with rheumatoid factor positive rheumatoid arthr 2004 Mar We observed 10-year radiographic outcomes in patients with rheumatoid factor positive rheumatoid arthritis prospectively. Group I, II, and III comprised 87, 125, and 89 consecutive subjects with disease duration at presentation of less than 4, 4-24, and 25-255 months, respectively. Initial therapy was with combinations of pulse intravenous (i.v.) methylprednisolone (0-125 mg), cyclophosphamide (100-200 mg), methotrexate (MTX, 5-15 i.v. mg/week) and simultaneous oral cyclosporin A (CSA, 25 mg bid/tid). After disease was controlled i.v. therapy was tapered and switched to oral MTX + CSA. Outcomes from the Larsen Index and Erosive Joint Count were compared in cases and in dropouts with baseline and each other. Significant improvement in the Larsen Index and Erosive Joint Count was observed in Group I (p < 0.0001). In Group II and III the improvement or deterioration was not significant. The Larsen Index and Erosive Joint Count deteriorated significantly in the dropouts compared with baseline and cases (p < 0.0001). In conclusion, in early RA, in a Malayo-Polynesian patient sample, radiological progression could be halted with aggressive combination treatment.
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