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16870092 Treatment continuation rate in relation to efficacy and toxicity in long-term therapy with 2006 May OBJECTIVE: To evaluate the effectiveness of disease-modifying antirheumatic drugs, namely, methotrexate (MTX), sulfasalazine (SSZ) and bucillamine (BUC) at low-doses (4, 6 or 8 mg MTX, 500 or 1,000 mg SSZ, and 100 or 200 mg BUC) in 1,358 patients with a follow-up of at least 12 months and more than 120 months. METHODS: Clinical assessments were based on the number of painful joints (NPJ) and that of swollen joints (NSJ), CRP level, erythrocyte sedimentation rate, rheumatoid factor level and morning stiffness before and after treatment. Results were evaluated on the basis of the duration of treatment for each drug with inefficacy or inadequate efficacy as one endpoint for discontinuation and adverse drug reactions (ADRs) as the other in single agent and combination therapy. The incidence and nature of ADRs in single and combination treatment are described. RESULTS: The effects of MTX, SSZ and BUC on clinical parameters were monitored over the first three months, and in particular, NPJs and NSJs were found to decrease significantly during single agent MTX or BUC treatment over 108 months. CRP levels remained significantly improved for more than 120 months with MTX. In the single and combination long-term treatments, continuation rate with inefficacy or inadequate efficacy as the end point achieved for each of the treatments were 83.1% for MTX, 76.0% for BUC, 68.5% for SSZ, and in the case of the combination treatments, these rates were 83.3% for MTX + BUC and 71.0% for MTX+SSZ. Continuation rates using ADRs as the end point were 88% for SSZ, 79.6% for BUC and 79.4% for MTX. The incidences of ADRs for the various treatments were: MTX 22.2%, SSZ 11.0%, BUC 20.6%, MTX + BUC 30.0% and MTX + SSZ 31.2%. CONCLUSION: MTX showed the highest efficacy even though it was administrated at a low dose (6-8 mg), as a single agent or in combination with other treatment. However, in combination treatments, the continuous duration of treatment ending in ADRs as the end point were lower than those in single treatments with MTX, SSZ and BUC.
16322085 Trends in disease modifying antirheumatic drug prescription in early rheumatoid arthritis 2006 Aug OBJECTIVE: To characterise temporal trends and factors associated with the prescription of disease modifying antirheumatic drugs (DMARDs) at the initial consultation in early rheumatoid arthritis (RA). METHODS: Data from 2584 patients with early RA at 19 hospitals were extracted from the Swedish Rheumatoid Arthritis Register for the period 1997-2001. Disease characteristics and DMARD prescription at first consultation with the rheumatologist were investigated using cross tabulation and logistic regression. RESULTS: DMARD prescriptions, particularly for methotrexate, increased from 1997 to 2001 independently of patient characteristics. Stratification by hospital type showed that patients in district hospitals were less likely to be prescribed DMARDs than those in university hospitals (adjusted odds ratio (OR) = 0.53 (95% confidence interval (CI) 0.40 to 0.69), p<0.001), independently of confounding factors. Association of the DAS28 with the likelihood of DMARD prescription was greater among patients attending district hospitals (OR = 1.65 (1.34 to 2.02), p<0.001) than those at university hospitals (OR = 1.23 (1.07 to 1.41), p = 0.003) and county hospitals (OR = 1.34 (1.01 to 1.63), p = 0.003). Interaction testing indicated that the difference was significant (p = 0.007). CONCLUSIONS: Temporal trends in DMARD prescription indicate an increasingly aggressive approach to disease management among Swedish rheumatologists. However, the association of hospital type with DMARD prescription suggests that the adoption of research findings in clinical care varies considerably.
18673161 Impact of traditional therapies and biologics on cardiovascular diseases in rheumatoid art 2008 Jul In chronic inflammatory diseases such as rheumatoid arthritis (RA), systemic inflammation appears as an independent risk factor, contributing to increased cardiovascular mortality. This high cardiovascular mortality reveals the existence of accelerated atherosclerosis, the pathogenesis of which may be associated with traditional risk factors such as smoking, hypertension, dyslipidemia, deterioration of insulin sensitivity, and less traditional risk factors such as hyperhomocysteinemia, inflammatory conditions and endothelial dysfunction. Control of systemic inflammation theoretically provides a means of preventing this higher cardiovascular mortality among RA patients. In this review we address the question of the impact of anti-rheumatic drugs currently used in RA, such as non-steroidal anti-inflammatory drugs (e.g. non-selective or cyclooxygenase-2 selective inhibitors), steroidal anti-inflammatory drugs (glucocorticoids), traditional disease-modifying anti-rheumatic drugs (e.g. methotrexate) or biologics (e.g. anti-tumour necrosis factor alpha anti-tumour necrosis factor alpha) on cardiovascular diseases in RA patients. We also discuss the specific mechanisms involved in the differential cardiovascular effects of these therapeutic agents.
16503951 Pneumonitis associated with leflunomide: a profile of New Zealand and Australian reports. 2006 Mar BACKGROUND: Pneumonitis has very rarely been observed in patients taking leflunomide in clinical trials. Evidence is emerging that it is more frequent in clinical practice. AIM: The aim of this study was to investigate voluntary reports of suspected respiratory reactions to leflunomide held by the New Zealand Pharmacovigilance Centre (NZPhvC) and the Australian Adverse Drug Reactions Unit (ADRU) to ascertain if they fulfilled the criteria for pneumonitis and to define characteristics of this reaction. METHOD: Reports of respiratory adverse reactions attributed to leflunomide and received by the NZPhvC and the ADRU were analysed to identify those that were likely to be pneumonitis based on the criteria of Searles and McKendry. Features of these reports were examined to provide further information about this adverse reaction. RESULTS: The NZPhvC and the ADRU received 14 reports considered to be pneumonitis occurring in patients taking leflunomide. Two case reports fulfilled the Searles and McKendry criteria for definite or probable hypersensitivity pneumonitis. The patients in the remaining reports had radiological evidence of pulmonary infiltrates, an acute respiratory illness and no evidence of precipitating infection. In two cases the patients were taking leflunomide alone; one improved when it was withdrawn. In the other 12 cases, patients were taking leflunomide in combination with methotrexate. In nine of these 12 patients pneumonitis occurred after leflunomide was added to methotrexate, usually within 12-20 weeks. One of the two patients who died had possible previous methotrexate pneumonitis. Leflunomide washout with cholestyramine was used to treat three patients, one with life-threatening illness, with good results. CONCLUSION: This case series supports observations that leflunomide can cause pneumonitis either as monotherapy or in combination with methotrexate. The case histories indicate that prompt recognition is important to avoid life-threatening disease and support the use of cholestyramine to remove leflunomide.
17163236 Methotrexate and hepatic toxicity in rheumatoid arthritis and psoriatic arthritis. 2006 BACKGROUND: We set out in this study to demonstrate the adverse effect profile of methotrexate when used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in a district general hospital population, and to investigate the effect of alcohol consumption in these patients. METHODS: A prospective evaluation of 550 RA patients and 69 PsA patients was undertaken, controlling for confounding factors. Systematically randomised patients were further analysed regarding alcohol consumption. A transaminase level of three times the upper limit of normal on two or more occasions was taken to indicate hepatic injury. RESULTS: Gastrointestinal disturbance was the predominant adverse effect in RA patients (9.8%); hepatic disturbance was the most frequent in PsA patients (14.5%). Both groups had hepatic enzyme elevation; PsA patients were at significantly greater risk of elevated transaminases than RA patients (14.5% vs 7.5%, respectively, chi2 = 4.017). Alcohol consumption did not correlate with hepatic injury (mean 5.15 vs 6.6 alcohol units/week consumed by RA and PsA patients, respectively). CONCLUSION: Our data show methotrexate-treated PsA patients have a higher incidence of hepatotoxicity compared with methotrexate-treated patients with RA. It is proposed that psoriatic patients may be inherently more susceptible to methotrexate hepatotoxicity than are rheumatoid patients.
18021334 Population pharmacokinetic investigation of low-dose methotrexate in rheumatoid arthritics 2007 Dec OBJECTIVE: To estimate the population pharmacokinetics of low-dose methotrexate (MTX) in Japanese patients using nonmem, a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. METHOD: A total of 153 serum concentration measurements obtained from the 17 healthy volunteers and 17 patients with rheumatoid arthritis were collected. Analysis of the pharmacokinetics of MTX was accomplished using a two-compartment pharmacokinetic model with first-order absorption. The effect of a variety of developmental and demographic factors on MTX disposition was investigated. RESULTS: The final pharmacokinetic parameters were CL/F (L/kg/h) = 0.177 x 0.394MULT, V1/F (L/kg) = 0.0501, Q/F (L/kg/h) = 0.056, V2/F (L/kg) = 0.368, ka (h-1) = 0.503, where CL is total body clearance, V1 and V2 is apparent volume of distribution in the central and peripheral compartments, k(a) is absorption rate constant, Q is intercompartmental clearance and MULT = 1 for patients received multiple dosing and zero otherwise. The interindividual variabilities in CL, Q and V1 were 25.7%, 22.3% and 217.9%, respectively, and the residual variability was 17.8% as a coefficient of variation. Because of the lake of information on data set we were unable to characterize the interindividual variability for V2 and ka. CONCLUSION: Clinical application of the model to patient care may permit selection of an appropriate dosage to achieve target MTX concentrations, thus enabling the clinician to achieve the desired therapeutic effect in Japanese patients. However, the MTX dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug.
17530704 Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in e 2007 Jun OBJECTIVE: To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial infections in routine care. METHODS: This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization. RESULTS: The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0-2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5-3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX. CONCLUSION: In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.
16519794 Enhanced expression of mRNA for nuclear factor kappaB1 (p50) in CD34+ cells of the bone ma 2006 Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-alpha and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)kappaB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-alpha. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFkappaB1 (p50), NFkappaB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFkappaB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFkappaB2 and RelA. The expression of NFkappaB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFkappaB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-alpha without influencing their viability and capacity to produce beta2-microglobulin. These results indicate that the enhanced expression of NFkappaB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-alpha and, thus, in the pathogenesis of RA.
17105853 Evaluation of a modified ACR20 scoring system in patients with rheumatoid arthritis receiv 2006 Dec OBJECTIVE: To evaluate a modified American College of Rheumatology 20 (mACR20) scoring system for patients with rheumatoid arthritis. METHODS: The data were evaluated from one study on patients with methotrexate (MTX)-naive early rheumatoid arthritis (ERA) and another study on patients with DMARD-refractory late rheumatoid arthritis (LRA). For mACR20 scoring, acute-phase reactant measurements were excluded, and 20% improvement from baseline was determined by 2 or 3 of the 4 remaining ACR components. RESULTS: For full joint counts with data from patients with ERA, marked differences favoured 25 mg etanercept (ETN) over 10 mg ETN by using the unmodified ACR20 (69% v 55%), the mACR20(3 of 4) (63% v 49%) and the mACR20(2 of 4) (72% v 58%). An assessment of 28 joints showed similar findings. In the trial on patients with LRA, considerably more patients in both ETN groups achieved a clinical response compared with placebo by using the ACR20, the mACR20(3 of 4) and the mACR20(2 of 4), whether using full or 28 joint counts. The mACR20(3 of 4) and full joint counts with data on patients with ERA showed a marked difference between the MTX and 10 mg ETN groups (63% v 49%), which was not observed with the ACR20. CONCLUSION: Patterns of improvement indicated by mACR20 scores were consistent with standard ACR20 scores.
16834969 [Effects of traditional Chinese medicine for invigorating spleen to resolve dampness and d 2006 Jul OBJECTIVE: To observe the clinical effects of Xinfeng Capsules (XFC), a traditional Chinese medicine for invigorating the spleen to resolve dampness and dredging collaterals, on patients with rheumatoid arthritis (RA) and anemia, and to investigate its mechanism. METHODS: Forty patients with RA and anemia were divided into three groups: XFC-treated group (n=20), Tripterygium glycosides Tablets (TGT)-treated group (n=10) and methotrexate (MTX)-treated group (n=10). The patients in each group took corresponding medicine for three months. The response rates of the three groups were evaluated after treatment. The general symptoms and specific signs and symptoms of RA were observed before and after the treatment. The indexes of blood routine examination and some other laboratory indexes such as erythrocyte sedimentation rate (ESR), and blood levels of rheumatoid factor (RF), iron, C-reaction protein (CRP), immunoglobins (Ig), complements 3 and 4, tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) and erythropoietin (EPO) were all examined and compared before and after treatment. RESULTS: The total response rate in the XFC-treated group was similar to those both in the TGT-treated and MTX-treated groups. The effects on relieving specific symptoms of RA in the three groups were also similar. The ESR and serum levels of RF, CRP, IgG, IgA and IgM were all decreased after treatment as compared with those before treatment in the three groups, and there were no significant differences among those laboratory indexes in the three groups after treatment. The XFC displayed more obvious effects on improving the general symptoms of patients with RA and anemia, increasing the blood levels of hemoglobin, iron and IL-10, while decreasing the serum level of TNF-alpha and regulating the serum EPO level, as compared with those in the TGT-treated and MTX-treated groups. CONCLUSION: The XFC for invigorating the spleen to resolve dampness and dredging collaterals was developed on the basic principle of regulating spleen. It can obviously improve the symptoms and laboratory indicators of RA. Such effects may be related to maintaining the balance of cytokines, regulating the serum level of EPO and increasing the serum iron level in patients with RA and anemia.
17158431 Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients wi 2006 Dec BACKGROUND: Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans. OBJECTIVE: The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA). DESIGN: Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study. RESULTS: Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function. CONCLUSIONS: Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.
19000788 Differential influences of bucillamine and methotrexate on the generation of fibroblast-li 2009 Jan We have recently demonstrated that bone marrow CD34+ cells from rheumatoid arthritis (RA) patients displayed abnormal capacities to respond to TNF-alpha and to differentiate into fibroblast-like cells producing MMP-1 (type B synoviocyte -like cells). The current study examined the effects of representative potent disease-modifying antirheumatic drugs, including bucillamine (BUC) and methotrexate (MTX) on the in vitro generation of fibroblast-like cells from RA bone marrow CD34+ cells. CD34+ cells purified from bone marrow specimens of 8 patients with active RA were cultured in the presence or absence of pharmacologically attainable concentrations of intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC or MTX (20 nM). After incubation for 28 days, the generation of fibroblast-like cells was assessed under phase-contrast light microscopy and the concentrations of MMP-1 and VEGF in the culture supernatants were measured by ELISA. BUC-ID, but not MTX, significantly suppressed the generation of fibroblast-like cells from RA bone marrow CD34+ cells stimulated with SCF, GM-CSF and TNF-alpha (p=0.024 as determined by Wilcoxon signed rank test). Accordingly, BUC-ID, but not MTX, significantly suppressed the production of MMP-1 (p=0.017) and VEGF (p=0.017) by RA bone marrow CD34+ cells, without inhibition of beta2-microglobulin production. These results demonstrate that BUC-ID, but not MTX, is a potent inhibitor of differentiation of fibroblast-like cells from RA bone marrow CD34+ cells. Since MTX, but not BUC, has been previously shown to influence on type A synoviocytes, the data provide rationale of combination of BUC and MTX in the treatment of RA.
17926823 Rituximab: new indication. In rheumatoid arthritis: for a few patients, with close monitor 2007 Oct (1) Methotrexate is often used as a first-line treatment for severe and worsening rheumatoid arthritis. TNF alpha antagonists (etanercept, infliximab and adalimumab) are second-line options. (2) Rituximab, a monoclonal antibody first used to treat lymphoma, is now also approved for the treatment of rheumatoid arthritis when at least one TNF alpha antagonist has failed. (3) There are three available comparative trials including about 1150 rheumatoid arthritis patients. The results indicate that rituximab is no more effective than methotrexate; a combination of rituximab + methotrexate is more effective than methotrexate alone (although only about half the patients meet the ACR 20% response criterion); and adding a steroid fails to improve effectiveness. (4) The adverse effect profile of rituximab in arthritis seems similar to that observed in lymphoma. In the short term, the main adverse effects are infusion hypersensitivity reactions, which are more frequent during the first infusion and can be partly prevented by premedication with a steroid. The other known risks are mainly infectious and cardiovascular. Follow-up is too short to rule out a possible increase in the risk of cancer. Gastrointestinal perforations have occurred in some lymphoma patients treated with rituximab. (5) In practice, when standard treatment fails, adding rituximab to methotrexate can be beneficial but requires close patient monitoring.
15645233 Influence of serum folic acid levels on plasma homocysteine concentrations in patients wit 2006 Jan The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.
19043773 Developing of granulomatous thyroiditis during etanercept therapy. 2009 Jun We describe a 32-year-old man who developed granulomatous thyroiditis (GT) during etanercept therapy for rheumatoid arthritis (RA). Fever and thyroid pain developed 8 months after administration of etanercept. Noncaseating epithelioid cell granulomas consistent with GT were detected in a thyroid biopsy. Tissue staining and cultures for bacteria, mycobacterium, and fungus were all negative. Etanercept therapy was withdrawn and steroids regime was indicated with clinical and laboratory improvement. A month after, the patient developed hypothyroidism and recurrence of RA. A year after, the patient is asymptomatic with rituximab, methotrexate, and levothyroxine therapy. We report a case of GT probably in an etanercept-induced granulomatous reaction context.
19014836 Pharmacokinetic and pharmacodynamic properties of TRU-015, a CD20-directed small modular i 2008 Oct BACKGROUND: TRU-015 is a small modular immunopharmaceutical protein drug that binds to CD20 and effectively depleted B cells in nonhuman primates. OBJECTIVE: The aim of this clinical study was to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties, immunogenicity, and tolerability of TRU-015 in patients with rheumatoid arthritis (RA). METHODS: This Phase I, open-label, dose-escalation clinical study was conducted at 4 medical centers in the United States. Patients with RA who were receiving stable-dose methotrexate were enrolled in 1 of 8 dose groups and received TRU-015 as a single IV dose of 0.015, 0.05, 0.15, 0.5, 1.5, 5, or 15, or 2 IV doses of 15 mg/kg, administered 7 days apart (30 mg/kg). Patients were enrolled in the next higher dose cohort based on the tolerability observed in the prior cohort. Prior to TRU-015 infusion, patients were premedicated with an antihistamine and acetaminophen and may have received a corticosteroid at the investigator's discretion. Serum samples were collected for analysis of PK properties (serum t((1/2))) and neutralizing antibodies to TRU-015; enzyme-linked immunosorbent assays and a cell-based neutralizing assay were used to evaluate samples from patients. PD response was measured using B-cell (CD19(+)-cell) count using flow cytometry at prespecified time points. Tolerability was assessed during drug infusion and at prespecified time points after infusion using physical examination and laboratory analysis. Patients were followed for >or=4 weeks and until B-cell recovery. RESULTS: Thirty-seven patients were enrolled. Most were female (81%) and white (95%); the mean age was 53 years. Serum t((1/2)) ranged from 12 to 19 days. B-cell depletion generally increased in degree and duration with increasing doses. No neutralizing antibodies to TRU-015 were detected. Mild adverse events (AEs) included back pain, headache, peripheral edema, and upper respiratory infection (5 patients each). Mild urticaria occurred in 1 patient. Grade 3 AEs included hypertension, arthralgia, and urticaria and bronchospasm (1 patient each). No dose-limiting toxicity was found. CONCLUSIONS: In this small population of patients with RA, the C(max) and the AUC appeared to increase in a dose-proportional manner. The mean t((1/2)) ranged from 12 to 19 days. TRU-015 was associated with dose-dependent B-cell depletion and an acceptable tolerability profile.
18638711 Differential effect on symptoms treated with traditional Chinese medicine and western comb 2008 Aug OBJECTIVE: This study is designed to compare the therapeutic effects and safety of traditional Chinese medicine (CM) therapy and western combined therapy (WM) in the treatment of rheumatoid arthritis (RA). METHODS: After 24 weeks' treatment, the efficacy, safety and the improvement on symptoms of traditional Chinese medicine in 199 patients and western medicine therapy in 197 patients of RA were analyzed. CM therapy included Glucosidorum Tripterygll Totorum tablet and Yishen Juanbi Tablet. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The American College of Rheumatology (ACR) 20, 50 and 70 responses were employed as primary end-point analysis and the 18 symptoms as secondary end-point analysis. All data were analyzed on SPSS11.5 statistical package. RESULTS: The ACR20 and ACR50 responses in WM were higher than in CM group, but more improvement on the symptoms and less adverse events were observed in CM therapy. The 18 CM symptoms in RA could be grouped into four symptom combinations with factor analysis method. The factor loading value difference (which reflects the degree of improvement) in responded cases was lower than in non-responded cases in the symptom combination 1. The loading value difference in both responded and non-responded cases in CM treated patients were higher than those in WM treated group in the symptom combination 2 and 3. CONCLUSIONS: WM combined therapy was more effective in the treatment of RA in ACR20 evaluation, but more improvement on CM symptoms were seen in the CM therapy.
16778342 Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis. 2006 Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in Japan since August 2003. Leflunomide-induced interstitial pneumonitis has not been reported as an adverse effect in other countries. We report a suspected case of leflunomide-induced interstitial pneumonitis. A 77-year-old woman with rheumatoid arthritis and a history of methotrexate-induced pneumonitis developed sudden-onset dyspnea on exertion about 2 months after the administration of leflunomide. She maintained a high concentration of an active metabolite of leflunomide for more than 3 weeks after withdrawal of the drug. She did not respond to treatment and died. Leflunomide must be administered with caution to patients with a history of interstitial pneumonitis or drug-induced pneumonitis. If leflunomide-induced pneumonitis is suspected, the plasma concentration must be immediately checked, along with elimination and withdrawal of the medication.
17874627 [Leflunomide as a second choice treatment in patients with rheumatoid arthritis]. 2007 Jun Leflunomide is a relatively new disease modifying antirheumatic drug (DMARD) and a number of studies evaluating its effectiveness and safety in daily medical practice is limited. THE AIM OF THE STUDY: Evaluation of effectiveness and safety of leflunomide treatment in patients with active rheumatoid arthritis in whom methotrexate was ineffective or contraindicated. MATERIAL AND METHODS: Eighty one patients (66 women and 15 men) with RA diagnosed according to ARA (The American Rheumatism Association) criteria were included in the study. The mean age was 57.6+/-11.7 years and the mean disease duration was 7.7+/-7.1 years. The inclusion criteria were: disease activity according to DAS28 (Disease Activity Score)>3.2 and contraindications to methotrexate or ineffective methotrexate treatment for at least 3 months. At the beginning of the study 49 of patients were treated with methotrexate in weekly dose of 17+4.2mg and 32 were not treated with DMARDs. Oral glicocorticosteroids in stable doses of 5-15mg of prednisone were given to 66 (77.7%) of them. There was no statistically significant difference in radiological progression of the disease according to Steinbrocker's scale between groups (treated and not treated with methotrexate). Monotherapy with leflunomide was started with loading dose of 100mg for 3 days, and then 20mg daily. Combination therapy was introduced without loading dose. Evaluation was performed monthly and included: duration of morning stiffness, pain and disease activity according to VAS (visual-analogue) scale, the number of tender and swollen joints, blood count, ESR, CRP, aminotransferases activity, and the presence and intensity of adverse reactions. The results of treatment were evaluated after 5 months in 37 of patients and adverse reactions which happened until the end of 5th month were evaluated in all included patients. RESULTS: The mean DAS28 values improved exponentially during consecutive months and the difference between them was statistically significant. Adverse reactions during 5 months of treatment were observed in 36(44,4%) of patients and in 6(7,4%) of cases the treatment had to be stopped because of side effects. The frequency of adverse reactions was similar in monotherapy and combination therapy group. CONCLUSIONS: Leflunomide therapy can be effective in patients with active rheumatoid arthritis in whom methotrexate is contraindicated or insufficient. Combination of leflunomide with methotrexate is safe and does not increase the frequency of adverse reactions.
17642229 [Biologics: current therapeutic strategies for rheumatoid arthritis]. 2007 Jul Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with DMARD as early as possible and among multiple DMARD methotrexate (MTX) is considered the anchor drug and should be used first. However, even use of MTX often fails to control disease activity and to prevent structural damage and, thereby, more effective treatment strategies are needed. TNF-alpha plays a pivotal role in the pathological processes of RA by accumulation of inflammatory cells and the self perpetuation of inflammation, leading to cartilage and bone destruction. Biologics targeting TNF-alpha with MTX, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. Herein I review the evidence-based medicine that addresses these issues and document an era of anti-cytokine therapeutics which is beginning to emerge.