Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 15098369 | [Treatment of rheumatoid arthritis]. | 2003 | Basic principles of drug treatment for rheumatoid arthritis are described. Nonsteroidal antirheumatic drugs are available and efficacious and part of almost each therapeutic approach. Corticosteroids have antiinflammatory and symptomatic properties with fast signs of improvement and potential anti-erosive action. Methotrexate, sulfasalazine, chloroquine, azathioprin, cyclosporin and leflunomide are the most frequently administered disease modifying antirheumatic drugs with delayed clinical effects. The biologic agents (anticytokines) offer new opportunities because they inhibit proinflammatory cytokines activity and very first stages of inflammation. Combination therapy of almost all drugs is eligible if it is efficacious and not increasing risk of adverse events. The outcome of rheumatoid arthritis is related to early diagnosis and early treatment with monitoring of efficacy and adverse events. | |
| 12548440 | Prevalence of dermatophytosis in patients with rheumatoid arthritis. | 2003 Jan | OBJECTIVE: The prevalence of dermatophytic infections in rheumatoid arthritis is unknown. This study investigated the prevalence of dermatophytosis in patients with rheumatoid arthritis and the relationship between sulfasalazine, low-dose methotrexate and steroid therapy. METHODS: We examined 53 consecutive patients with rheumatoid arthritis for evidence of dermatophytosis and compared them 55 with age- and sex-matched, nonimmunocompromised controls recruited from the low back pain population. Nail scrapings were obtained from the subjects, and the clinical diagnosis of dermatophytosis was confirmed with a potassium hydroxide preparation. RESULTS: In 32% of the rheumatoid arthritis population we found dermatophytosis, compared with 16% of the control group, although statistical significant was only borderline. Tinea pedis was the most frequent type of dermatophytosis in both groups. The prevalence of dermatophytosis in patients receiving sulfasalazine, low-dose methotrexate, and steroid therapy was not found to be significantly increased. CONCLUSIONS: This study shows a slightly higher prevalence of dermatophytosis in rheumatoid arthritis population than in controls. Sulfasalazine, low-dose methotrexate, and steroid therapy had no effect on the prevalence of dermatophytic infections in patients with rheumatoid arthritis. | |
| 15517623 | Effects of Prosorba column apheresis in patients with chronic refractory rheumatoid arthri | 2004 Nov | OBJECTIVE: Since the approval of Prosorba column apheresis therapy (PCT) for rheumatoid arthritis (RA) in 1999 there have been multiple requests for additional information on the response rate of PCT used commercially in rheumatology practice settings. METHODS: Data were collected in a noninterventional prospective fashion on patients with RA who qualified for the PCT treatment per the package insert. There were 91 patients who completed the 12 prescribed treatments. There was no washout of other drugs [i.e., disease modifying antirheumatic drugs (DMARD), biologics]. An initial baseline assessment was performed prior to first treatment and then up to 4 additional assessments were performed at Weeks 9, 16, 20, and 24. Criteria for ACR20 were noted in order to assess response rate, and commercial adverse event reporting was used to record serious/unanticipated adverse events. RESULTS: There was a response rate of 53.8% (measured as ACR20 response or better) in these patients with previously refractory RA. The individual criteria showed a much greater improvement than reflected by ACR20; for example, this response included a 52% improvement in joint tenderness, 40% improvement in swelling, 42% improvement in patient's pain, 38% improvement in patient's global response, and 48% improvement in physician's global scores (76% of responders had measured ACR20 by Week 16 and 100% by Week 24). The actual measurement of an ACR response generally occurred during assessments at Week 16; however, most patients who respond will state they felt improvement some time between Weeks 8 and 12. There were no assessments between Weeks 9 and 16 so the actual week of improvement could not be identified by ACR criteria. Some patients stated that they felt improvement began closer to the 6th week. Most responders were concurrently taking biologics or DMARD, e.g., methotrexate and etanercept, despite previously inadequate RA response to those medications. CONCLUSION: This postmarketing study of PCT used commercially in 59 rheumatology practice settings supports the safety and efficacy of this treatment regime in selected patients with RA and compares favorably with the initial sham controlled clinical trial. PCT is a relatively underutilized choice for the management of active, aggressive RA. | |
| 15248204 | Retardation of joint damage in patients with early rheumatoid arthritis by initial aggress | 2004 Jul | OBJECTIVE: To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score. RESULTS: A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively. CONCLUSION: Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA. | |
| 12817092 | Clinical and radiological effects of anakinra in patients with rheumatoid arthritis. | 2003 May | Interleukin-1 (IL-1) is a proinflammatory cytokine that plays a pivotal role in the pathophysiology of rheumatoid arthritis (RA). Inhibiting the activities of IL-1 at the receptor level with the recombinant human IL-1 receptor antagonist anakinra (Kineret; Amgen Inc., Thousand Oaks, CA) is a new therapeutic option for the management of patients with RA. Randomized, placebo-controlled trials have demonstrated that anakinra, alone and in combination with methotrexate, improves the signs and symptoms of RA. Anakinra also produces improvements in patient functionality and health-related quality of life, as measured by the Health Assessment Questionnaire and the Nottingham Health Profile, and reduces the number of productivity days missed due to illness. Furthermore, an initial study indicates that anakinra retards the progression of radiographic joint damage. Such clinical findings suggest that anakinra is an important addition to the rheumatology treatment armamentarium. | |
| 12673886 | Expression of folylpolyglutamyl synthetase predicts poor response to methotrexate therapy | 2003 Jan | OBJECTIVE: The enzyme folylpolyglutamyl synthetase (FPGS) is involved in the resistance to methotrexate in tumor cell lines. The aim of the present study was to determine the impact of FPGS mRNA expression on resistance to methotrexate therapy in patients with rheumatoid arthritis (RA). METHODS: We determined the expression of FPGS mRNA using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) in 141 patients with RA. All patients received methotrexate therapy. The primary outcome measures were disease activity as determined by a disease activity score (DAS) and response to therapy. RESULTS: Seventy-eight of 141 patients (55%) showed expression of FPGS mRNA. FPGS mRNA expression was not associated with age, sex, disease duration, white blood cell count, erythrocyte sedimentation rate, C-reactive protein (CRP), number of swollen joints, number of painful joints, and combined therapy with other disease-modifying antirheumatic drugs (DMARDs) or additional corticosteroids. The response rate to methotrexate therapy was 44% for the total study population. Patients without FPGS mRNA expression showed a significantly higher response rate than patients with FPGS mRNA expression (57% versus 33%; p = 0.005). Multivariate logistic regression analysis revealed that female sex (p = 0.009) and FPGS mRNA expression (p = 0.004) were independent predictive factors for failure to achieve a response to methotrexate therapy. CONCLUSION: FPGS mRNA expression is an independent predictive factor associated with poor response to methotrexate therapy in RA patients. | |
| 14637281 | Moderate hyperhomocysteinaemia and immune activation in patients with rheumatoid arthritis | 2003 Dec | BACKGROUND: Moderate hyperhomocysteinaemia related to folate deficiency has been described in patients with cardiovascular risk and also in patients with autoimmune diseases including rheumatoid arthritis (RA). METHODS: In 33 patients with RA, serum concentrations of homocysteine and cysteine, of B-vitamins folate and vitamin B(12), and of immune activation markers neopterin and soluble 75-kDa TNF-receptor (sTNF-R75) were measured. RESULTS: A significant proportion of patients presented with elevated homocysteine and cysteine concentrations in comparison to reference ranges of healthy control persons. Moderate hyperhomocysteinaemia coincided with decreased serum folate and with higher concentrations of sTNF-R75 and neopterin, but it was rather independent from methotrexate (MTX) therapy. CONCLUSIONS: The coincidence of higher homocysteine and lower folate concentrations with increased concentrations of immune activation markers in patients with RA suggests that immune activation could be involved in the development of hyperhomocysteinaemia. | |
| 15229948 | Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: result | 2004 Jul | OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA). METHODS: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis. CONCLUSION: We found no negative effect of low dose MTX on BMD in women with RA. | |
| 15242865 | A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous | 2005 Jan | OBJECTIVE: To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis. METHODS: 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study. RESULTS: Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups. CONCLUSIONS: At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis. | |
| 12180721 | Effectiveness profiles and dose dependent retention of traditional disease modifying antir | 2002 Aug | OBJECTIVE: To determine the fate of traditional disease modifying antirheumatic drugs (DMARD) in the longer term, with special respect to dose related effects on drug retention rates, efficacy, and toxicity. METHODS: Historical analysis of DMARD therapies in 593 patients, comprising a total of 1319 courses of DMARD over a period of 2378 patient-years of therapy. DMARD dosages, treatment durations, and reasons for discontinuation, and measures of C-reactive protein and erythrocyte sedimentation rate were analyzed. Drug retention rates were estimated by Kaplan-Meier analysis. RESULTS: Methotrexate (MTX), chloroquine, and sulfasalazine (SSZ) emerged as the drugs most commonly applied during the past 15 years, whereas gold salts and D-penicillamine became less frequently used during the past decade. Therapies had to be terminated mostly for adverse events (42%) or inefficacy (37%). Patients taking high dose therapy had significantly longer median retention rates than those taking low doses (SSZ 34 vs 7 mo; MTX 73 vs 39 mo). Toxicity, ratherthan inefficacy, was the main reason for discontinuation of MTX and SSZ at low doses (p < 0.001). Median retention rates lasted < 24 mo for most DMARD, except for high dose MTX (> 36 mo). CONCLUSION: MTX, SSZ, and antimalarials have become the most commonly used traditional DMARD for rheumatoid arthritis. Their use is more often limited by toxicity than by inefficacy. If tolerated, they can be retained for long periods of time. | |
| 12632413 | An index of the three core data set patient questionnaire measures distinguishes efficacy | 2003 Mar | OBJECTIVE: To evaluate the capacity of a pooled index of only the 3 patient self-report questionnaire measures among the 7 American College of Rheumatology (ACR) core data set (Core Data Set) measures to distinguish efficacy of active treatment of rheumatoid arthritis (RA) with leflunomide or methotrexate versus placebo in a randomized, controlled clinical trial, and to compare the results with those obtained using the ACR 20% response criteria (ACR20), Disease Activity Score (DAS), and other pooled indices. METHODS: The 7 ACR Core Data Set measures of 1) joint swelling, 2) joint tenderness, 3) physician global assessment, 4) erythrocyte sedimentation rate (ESR), 5) functional disability, 6) pain, and 7) patient global assessment were combined into the following 5 pooled indices: "All Core Data Set" (all 7 measures), "Assessor Only" (measures 1-3), "Assessor + ESR" (measures 1-4), "Patient Only" (measures 5-7), and "Patient + ESR" (measures 4-7). The capacity of each of these 5 indices to detect differences between active treatment and placebo treatment was compared with that of the ACR20 and the DAS using 4 different analytic methods, each of which presented advantages and limitations. Agreement of the indices with one another and with the ACR20 and the DAS was analyzed according to pairwise kappa statistics and Z scores in multivariate logistic regression models. RESULTS: Each of the 5 indices, including "Patient Only," had a similar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clinical trial, according to each of 4 methods, at similar levels of statistical and clinical significance. CONCLUSION: A pooled index of patient self-report questionnaire Core Data Set measures appears to be as informative as ACR20 responses, DAS scores, and pooled indices of all and assessor-derived Core Data Set measures for distinguishing between active treatment and placebo treatment in this RA clinical trial. | |
| 14971085 | Mortality in rheumatoid arthritis patients treated with or without methotrexate. | 2003 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease associated with excess mortality. In 1974 a registry of RA patients was established at the Wichita Arthritis Center. It has been directed by its founder, Dr. Frederick Wolfe, ever since. The database for RA patients provided results for the present study and 1 of the 4 series reported previously. RESULTS: These are based on a consecutive series (after specific exclusions) of RA patients, 18 years of age and older, treated at the Wichita Arthritis Center, 1981 through 1999. During this period, 588 of the total 1240 RA patients were treated with methotrexate, and 652 patients did not receive any methotrexate. Total exposure amounted to 7584 patient-years, and total deaths numbered 191. An elaborate statistical method was developed by Wolfe and a team of Harvard epidemiologists to adjust for prognostic risk factors, which were higher in the methotrexate than in the non-methotrexate group. Detailed descriptive data were included in the database. Overall excess mortality in comparison with population rates was higher in the methotrexate than in the non-methotrexate group, but the unadjusted difference was not significant. Results for the 1981-1999 total Wichita cohort were compared with those of the 1974-1990 cohort and the 1983 Impairment Study (both before and after adjustment to the older age distribution of the Wichita patients). CONCLUSION: Mortality improved somewhat in the RA patients at the Wichita Center from 1974-1990 to 1980-1999. In the later period, mortality was lower in patients treated with methotrexate than in those not so treated. After the authors of the source article made adjustments for the increased RA severity in the patients treated with methotrexate, mortality was significantly lower in the methotrexate-treated group, with a mortality hazard ratio of 0.4 (95% confidence interval 0.2-0.8). | |
| 15286005 | Association between baseline radiographic damage and improvement in physical function afte | 2005 Jan | OBJECTIVES: To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment. METHODS: 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab (3 mg/kg or 10 mg/kg every four or eight weeks) for 54 weeks (the ATTRACT trial). Data on clinical outcomes and physical function (assessed by the health assessment questionnaire (HAQ)) were collected. Structural damage was assessed using the van der Heijde modification of the Sharp score. Odds ratios (OR) for factors associated with severe functional disability (HAQ > or =2.0) at baseline were estimated using multiple logistic regression analyses, and baseline factors related to the change in physical function after treatment at week 54 were determined. RESULTS: Baseline radiographic scores were correlated with baseline HAQ scores. After adjustment for demographic characteristics in the logistic regression model, baseline disease activity scores, radiological joint damage, fatigue, and morning stiffness were found to be associated with severe functional disability (HAQ >2.0), with OR values of 2.00 (1.53 to 2.63), 1.82 (1.15 to 2.87), 1.19 (1.05 to 1.34), and 1.07 (1.01 to 1.13), respectively. In multiple linear regression analysis, physical disability, joint damage, and fatigue at baseline were correlated with less improvement in physical function after treatment. Infliximab treatment was associated with greater improvement in physical function. CONCLUSIONS: Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment, underlining the importance of early intervention to slow the progression of joint destruction. | |
| 14969067 | Databases of patients with early rheumatoid arthritis in the USA. | 2003 Sep | Several databases of patients with early rheumatoid arthritis (RA) have been established in the USA. The University of Tennessee at Memphis Cohort was organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset of < or = 6 months who met the 1958 American Rheumatism Association (ARA) criteria for at least probable RA. Two important observations from this database were that many patients seen within the first 6 months of meeting the criteria for probable RA have a self-limited rather than progressive disease, and that progressive disease is predicted by a high number of baseline swollen and tender joints. The National Institutes of Health (NIH) cohort of patients with peripheral synovitis for > or = 6 weeks but < 12 months in at least one peripheral joint was established in 1994. At the one-year follow-up, 45% of the patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated arthritis. The number of active joints, rather than meeting the criteria for RA, was the primary determinant of function and performance after one year. The Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or = 6 swollen and > or = 9 tender joints, and no previous treatment with disease modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the validity of self-report joint counts. American College of Rheumatology 20% improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57% of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of patients prior to the availability of biologic agents. The North American Cohort of Patients with Early RA (SONORA), which included patients with symptoms for > 3 but < 12 months, indicated that methotrexate (MTX) was the most frequently prescribed DMARD, being taken by more than half the patients. The Consortium for the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA repository has enrolled 123 African-American patients with early RA of less than 2 years' duration to analyze genetic and non-genetic factors associated with disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients with early RA (< 3 years) was established in 2001. In this registry, MTX was the first DMARD used in 83% of patients, and most patients would not meet the criteria for inclusion in recent clinical trials of biological agents. Further observation of recent cohorts of patients with early RA over the next decade should be informative regarding whether aggressive intervention strategies and new DMARDs and biologic agents lead to improved long-term outcomes. | |
| 15200343 | Biological agents for rheumatoid arthritis: targeting both physical function and structura | 2004 | Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease of multifactorial aetiology. The pivotal role of proinflammatory cytokines in the pathogenesis and perpetuation of synovitis has been demonstrated in basic research since the late 1980s and in clinical research since the early 1990s. Biological agents are monoclonal antibodies or recombinant forms of natural inhibitory molecules which selectively interact with molecules or cell receptors affecting immune or inflammatory processes. In RA, etanercept, infliximab and adalimumab are currently available to target tumour necrosis factor (TNF) and an interleukin (IL)-1 receptor antagonist is available to target IL-1 activity. Trials have shown benefits as monotherapy, although the best results for disease control are seen when biological agents are coadministered with methotrexate. The use of these agents in clinical trials and in practice has resulted in dramatic improvements in RA disease control, and delay and prevention of radiographic damage. The remarkable benefits to patients in well-being, quality of life and function, and the speed of onset of action are reminiscent of the early days of corticosteroid use. Ten years after the first clinical trials of anti-TNF therapies, the adverse effect profile is evolving and includes, for anti-TNF therapy, an increased risk of infections associated with immune suppression, injection and infusion reactions, and a risk of drug induced autoimmune syndromes such as systemic lupus erythematosus. Where these drugs are affordable, the prognosis of individuals for control of severe RA is better than ever before. This manuscript summarises the clinical trial results and post-marketing information regarding the biological agents currently in use for RA. | |
| 12926656 | Reduced burden of disease and improved outcome of patients with rheumatoid factor positive | 2003 Aug | Our objective was to determine outcome and burden of disease in a 10 year study of patients with rheumatoid factor positive rheumatoid arthritis (RF+ RA) compared with study dropouts. Three hundred and one consecutive subjects with disease duration of 3-255 months at presentation were enrolled. The acute (as measured by C-reactive protein, CRP) and chronic (by erythrocyte sedimentation rate, ESR) phases of RF+ RA were suppressed by pulse intravenous (IV) combination of low dose methylprednisolone (MPS) + cyclophosphamide (CYC) for 3 consecutive days and weekly intravenous methotrexate (MTX) with simultaneous oral cyclosporine (CSA) + mycophenolate mofetil (MPM). After achieving negative CRP and ESR < 40 mm/h, IV therapy was tapered and switched to oral low dose MTX+CSA+MPM until negative CRP titer and ESR < 25 mm/h (men < 15 mm) Westergren were achieved. American Rheumatism Association (ARA) functional classification measured disability. Dropouts did not complete the study for various reasons. At baseline, cases and dropouts were comparable in age and sex distribution, including mean age, disease duration, disease features, and associated conditions. Mortality in 274 cases was 2.9% versus 25.9% in dropouts. ARA functional class in cases decreased from 3.2 + 0.7 to 1.4 + 0.3 and in dropouts was 3.2 + 0.6 at baseline versus 3.5 + 0.5 at outcome. Disability of dropouts was significantly worse compared with cases. In dropouts, more associated conditions occurred than in cases. The burden of disease and outcomes were significantly worse in dropouts compared with cases. | |
| 14639053 | Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. | 2003 Dec | Hydroxychloroquine (HCQ) is an antimalarial drug that is also used as a second-line treatment of rheumatoid arthritis (RA). Clinically, the use of HCQ is characterized by a long delay in the onset of action, and withdrawal of treatment is often a result of inefficacy rather than from toxicity. The slow onset of action can be attributed to the pharmacokinetics (PK) of HCQ, and wide interpatient variability is evident. Tentative relationships between concentration and effect have been made, but to date, no population PK model has been developed for HCQ. This study aimed to develop a population PK model including an estimation of the oral bioavailability of HCQ. In addition, the effects of the coadministration of methotrexate on the PK of HCQ were examined. Hydroxychloroquine blood concentration data were combined from previous pharmacokinetic studies in patients with rheumatoid arthritis. A total of 123 patients were studied, giving the data cohort from four previously published studies. Two groups of patients were included: 74 received hydroxychloroquine (HCQ) alone, and 49 received HCQ and methotrexate (MTX). All data analyses were carried out using the NONMEM program. A one-compartment PK model was supported, rather than a three-compartment model as previously published, probably because of the clustering of concentrations taken at the end of a dosing interval. The population estimate of bioavailability of 0.75 (0.07), n = 9, was consistent with literature values. The parameter values from the final model were: Cl = 9.9 +/- 0.4 L/h, V = 605 +/- 91 L, ka = 0.77 +/- 0.22 hours(-1), t(tag) = 0.44 +/- 0.02 hours. Clearance was not affected by the presence of MTX, and, hence, steady-state drug concentrations and maintenance dosage requirements were similar. A population PK model was successfully developed for HCQ. | |
| 15526504 | Chronic hepatitis C virus infection mimicking rheumatoid arthritis. | 2003 | We present the case of a young female patient diagnosed two years ago with rheumatoid arthritis (AR) for which she is taking methotrexate (MTX), who develops cutaneous lesions highly suggestive of porphyria cutanea tarda, diagnosis confirmed by biochemical means. It is noteworthy that she was regularly taking oral contraceptives until the moment of appearance of the skin lesions. The association of those two illnesses, particularly in the case of MTX treatment can raise some problems regarding the potential direct causality relationship. This is why we tried a new diagnostic hypothesis: is chronic hepatitis C virus infection, hypothesis that we verified by means of the presence of anti-VHC and of RNA-VHC. It is well known now the association between chronic viral C infection, rheumatoid syndrome and porphyria cutanea tarda (PCT). The latter are extrahepatic manifestations of that viral infection, thus representing a major indication for antiviral treatment. Our patient received that treatment and she had a very good outcome of the skin lesions. We suggest that the differential diagnosis of any arthritis should always comprise chronic hepatitis C viral infection. | |
| 11953965 | Early and aggressive treatment of rheumatoid arthritis patients affects the association of | 2002 Apr | OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA. | |
| 12087885 | [Changes in clinical and laboratory findings on oxidation metabolism in lymphocyte membran | 2002 | The study of the effects of intensive treatment on activity of free-radical oxidation in lymphocyte membranes was conducted in 15 rheumatoid arthritis (RA) patients with systemic involvement, stage II-III activity who had failed previous basic therapy because of unefficiency or intolerance. The synchroneous programmed intensive therapy was performed in 3 stages. Stage 1: three sessions of plasmapheresis with 3 day intervals, synchronous introduction of 30 mg methotrexate and 500 mg methylprednisolone. Stage 2: the same procedures once a week for the following 3 weeks. Stage 3: a monthly intensive therapy for 3 months. After the end of stage 3 all the patients received methotrexate 7.5 mg weekly per os for 6 months. The above intensive therapy of RA patients had an antiinflammatory effect, changed peroxidation reactions in lymphocyte membranes by lowering the level of pro-oxidants and stimulation of antioxidant system. No positive changes in the lipid status occurred. |