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ID PMID Title PublicationDate abstract
17203006 Drug Insight: resistance to methotrexate and other disease-modifying antirheumatic drugs-- 2007 Jan The chronic nature of rheumatoid arthritis (RA) means that patients require drug therapy for many years. Many RA patients, however, have to discontinue treatment because of drug-related toxic effects, loss of efficacy, or both. The underlying molecular cause for loss of efficacy of antirheumatic drugs is not fully understood, but it might be mediated, at least in part, by mechanisms shared with resistance to anticancer drugs. This Review outlines molecular mechanisms that could be involved in the onset of resistance to, or the loss of efficacy of, disease-modifying antirheumatic drugs in RA patients, including methotrexate, sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, and leflunomide. The mechanisms suggested are based on findings from experimental laboratory studies of specific drug-uptake and drug-efflux transporters belonging to the superfamily of multidrug-resistance transporters, alterations in intracellular drug metabolism, and genetic polymorphisms of drug transporters and metabolic enzymes. We also discuss strategies to overcome resistance and the current clinical studies aiming to predict response and risk of toxic effects. More in-depth knowledge of the mechanisms behind these features could help facilitate a more efficient use of disease-modifying antirheumatic drugs.
16960937 Plasma level of CXC-chemokine CXCL12 is increased in rheumatoid arthritis and is independe 2006 Sep OBJECTIVE: Several actions of the chemokine CXCL12 have potential relevance for rheumatoid arthritis (RA). Interaction with CXCR4, the unique receptor for CXCL12, stimulates angiogenesis, mononuclear cell trafficking into the joints, lymphoid-tissue-like rearrangement of T cells within the synovium, and chondrocyte release of cartilage-degrading metalloproteinases. We investigated the level of CXCL12 in plasma (p-CXCL12) as a marker of RA diagnosis, RA disease activity, and response to methotrexate (MTX) treatment. METHODS: A prospective study including 36 patients with RA (ACR criteria) of at least 6 months' duration, and 50 sex and age matched healthy controls. ELISA for CXCL12 was performed on plasma prior to and after 16 and 28 weeks of MTX treatment in the patients with RA and once in controls. RESULTS: The p-CXCL12 was 1855 +/- 145 pg/ml in RA patients and 1273 +/- 79 pg/ml in controls (p < 0.001). During the 28 weeks of MTX treatment, the ACR disease activity variables decreased, whereas the p-CXCL12 level remained constant and increased. P-CXCL12 was not correlated to any ACR disease activity variable at any time (p > 0.05). CONCLUSION: Patients with RA had a significantly and constantly increased p-CXCL12 level compared to controls. The p-CXCL12 level was independent of any ACR disease activity variables, as well as response to MTX treatment.
15975967 Duration of rheumatoid arthritis influences the degree of functional improvement in clinic 2006 Feb BACKGROUND: Functional capacity is an important outcome in rheumatoid arthritis and is generally measured using the Health Assessment Questionnaire disability index (HAQ). Functional limitation incorporates both activity and damage. Because irreversible damage increases over time, the HAQ may be less likely to show improvement in late than in early rheumatoid arthritis. OBJECTIVE: To determine the relation between sensitivity to change of the HAQ and duration of rheumatoid arthritis in reports of clinical trials. METHODS: Data were pooled from clinical trials that measured responses of HAQ scores at three or six months. The effect size of the HAQ was calculated and linear regression used to predict the effect size by duration of rheumatoid arthritis at group level. Treatment effect was adjusted for by including the effect sizes of pain scores and of tender joint counts as additional independent variables in separate models. Subgroup analysis employed contemporary regimens (methotrexate, leflunomide, combination therapies, and TNF inhibitors) only. RESULTS: 36 studies with 64 active treatment arms and 7628 patients (disease duration 2.5 months to 12.2 years) were included. The effect sizes of the HAQ decreased by 0.02 for each additional year of mean disease duration using all trials, and by 0.04/year in the subgroup analysis (p
17621798 [Current therapeutic strategy for rheumatoid arthritis]. 2006 Oct 19 The success of the treatment of rheumatoid arthritis depends primarily on early diagnosis. In most cases, basic therapy begins with methotrexate. Depending on the stage and course of the disease (radiographically detected early erosion and/or progression), basic immunosuppressive therapy can be combined or supplemented with cytokine antagonists. Furthermore, for specific indications, several alternative active substances (DMARD monotherapies) are available. Today the goal of therapy is always remission.
16358365 Patient, disease, and therapy-related factors that influence discontinuation of disease-mo 2006 Feb OBJECTIVE: A major challenge in management of rheumatoid arthritis (RA) is prediction of longterm response to disease-modifying antirheumatic drug (DMARD) treatment. Our objective was to identify the predictors of DMARD discontinuation in an incidence cohort of patients with RA followed continuously from their incidence date. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota, residents aged > or = 18 years diagnosed with RA (by 1987 American College of Rheumatology criteria) from January 1, 1955, to January 1, 1995, were followed longitudinally through their complete medical records until January 1, 2001. Detailed drug exposure data were collected on all DMARD and glucocorticoid regimens. Subjects were considered exposed to a DMARD if duration of use was > or = 30 days. Time to discontinuation of DMARD was estimated using survival analysis techniques. Andersen-Gill models with multiple events per patient were used to assess the influence of demographics, calendar time, comorbidities, disease characteristics [disease duration, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), joint counts, radiographic changes, nodules, RA complications], and therapy characteristics (DMARD use, singly or in combination, glucocorticoid use, first or subsequent regimen, effect of previous therapy) on time from DMARD initiation to discontinuation. RESULTS: The study population comprised 345 DMARD-treated patients (73% female) with mean age of 53.1 years and mean followup 15.4 years. Median time taking any DMARD was 16.0 months for the first, and 17.9 months for all regimens. Methotrexate (MTX) had the longest time to discontinuation, with a median of 30.3 months without folate, and 61.7 months with folate supplementation. Among the various disease characteristics examined, only higher ESR at DMARD initiation was significantly associated with a shorter time taking DMARD [hazard ratio (HR) 1.05 per 10 mm/h increase, 95% CI 1.02, 1.08]. In multivariable Andersen-Gill models considering all DMARD regimens, hydroxychloroquine use (HR 0.77, 95% CI 0.64, 0.92) and MTX use (HR with folate 0.39, 95% CI 0.30, 0.51; HR without folate 0.51, 95% CI 0.39, 0.67) were significantly associated with longer time to DMARD discontinuation, whereas prior MTX use (HR 1.96, 95% CI 1.57, 2.45) was associated with shorter time to DMARD discontinuation, after adjusting for age, sex, calendar year, Charlson comorbidity index, disease duration, and ESR at DMARD initiation. Disease duration was negatively associated with time to DMARD discontinuation; each 10 year increase in disease duration corresponded to a 14% decrease in the risk of discontinuation (HR 0.86, 95% CI 0.75, 0.98). CONCLUSION: Longer RA disease duration does not appear to increase the risk of DMARD discontinuation. However, high disease activity (as assessed by ESR) is associated with a higher likelihood of discontinuing DMARD. MTX failure may identify a subgroup of patients who are less likely to respond to other DMARD and therefore could be considered as candidates for biological therapies.
18828888 Are biologics more effective than classical disease-modifying antirheumatic drugs? 2008 Major achievements have been reached in the treatment of rheumatoid arthritis during past decades due to the recognition of methotrexate as an anchor drug for treatment of rheumatoid arthritis, due to the notion of a treatment window of opportunity in patients with recent-onset rheumatoid arthritis necessitating early aggressive therapy, due to the development of biologics and due to remission as a treatment target. Most biologics have a much faster onset of action than synthetic disease-modifying anti-rheumatic drugs, but presently there is no convincing evidence that biologic drugs have a superior clinical efficacy in comparison with the synthetic drugs. Biologics are, however, accompanied by less radiological deterioration.
19043967 [Pharmacogenomics of methrotexate: a strategy for a customized therapeutic scheme for pati 2008 Sep Rheumatoid arthritis (RA) is a common rheumatic disease in Mexico. Methotrexate (MTX) is a drug frequently used in the treatment of this disease. However, treatment discontinuation due to side effects is also common. Inter-individual differences in effectiveness and occurrence of side effects in RA patients treated with MTX (RA-MTX) have been reported. Several studies analyzed the presence of MTHFR C677T and A1298C polymorphisms in RA-MTX patients associated with effectiveness, side effects and toxicity. Given the high frequency of the MTHFR C677T polymorphism in Mexico, it is of utmost interest to determine the allelic and genotypic frequency of these polymorphisms in patients with RA-MTX. The use of molecular techniques, feasible in our country, such as PCR/RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) can allow us to identify these MTHFR genotypes among RA-MTX patients in order to target patients at risk of developing drug toxicity, side effects or better MTX efficacy. The ultimate goal is to develop individualized treatment, as promised by the field of pharmacogenomics.
18500458 Cryptogenic organizing pneumonia (COP), as presentation of rheumatoid arthritis. 2008 Nov We report a 65-year-old caucasian male, who presented cryptogenic organizing pneumonia (COP) as first manifestation of rheumatoid arthritis. The patient started with fever, myalgias and progressive dyspnea in October 2004. The chest X-ray (CXR) and high resolution computed tomographic scan (HRCT) showed diffuse alveolar exudates with air bronchogram in both the lungs. An open lung biopsy was done and the histological image was compatible with COP. Six months later, a diagnosis of RA was made. Treatment with oral methotrexate and etanercept was prescribed with improvement in symptoms, physical examination, and laboratory tests. Even though COP after the joint involvement is found more frequently in RA, in rare cases it could be the first manifestation of this illness.
18409573 [A case of rheumatoid arthritis complicated with methotrexate-induced pneumonitis and pneu 2008 Mar A 62-year-old woman with rheumatoid arthritis was given 4 mg/body methotrexate (MTX) every week and 5 mg prednisolone every day. She developed a severe cough starting in the evening after starting taking MTX and after a fever of 38 degrees and dyspnea appeared the patient was hospitalized. On admission, chest CT findings showed diffuse ground glass attenuation. Pathological findings of specimens obtained by transbronchial lung biopsy showed alveolitis with epithelioid cell granuloma. As a section of the specimen did not show cyst staining by Grocott stain, MTX-induced pneumonitis was diagnosed. The same day, methylprednisolone pulse therapy was started and trimethoprim-sulfamethoxazole (TMP-SMX) was given simultaneously, while MTX was discontinued. On hospital day 3, subsequent data showed a high serum level of beta-D glucan and a positive PCR result for Pneumocystis jiroveci in bronchoalveolar lavage fluid (BALF). Additional section of the specimen showed eosinophilic foamy areas on HE staining and cysts measuring 8 microm, consistent with the Pneumocystis jiroveci lesions by Grocott stain. We present a case of rheumatoid arthritis complicated by methotrexate-induced pneumonitis in which pneumocystis pneumonia was demonstrated by clinical and pathological findings.
16439441 Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in t 2006 Sep BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five common coding single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and Caucasians with rheumatoid arthritis and controls to assess whether there are differences in allele frequencies among these ethnic or racial groups and whether these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX. Another 308 subjects with rheumatoid arthritis who participated in observational studies, one group predominantly Caucasian and the other African-American, as well as 103 normal controls (53 African-Americans and 50 Caucasians) were used to characterise allele frequencies of these SNPs and their associated haplotypes. RESULTS: Significantly different allele frequencies were seen in three of the five SNPs and haplotype frequencies between Caucasians and African-Americans. Allele frequencies were similar between patients with rheumatoid arthritis and controls of the same racial or ethnic group. Frequencies of the rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid arthritis, these allele frequencies were 0.08 (p<0.001 compared with African-Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001), respectively. There was no association between SNP alleles or haplotypes and response to MTX as measured by the mean change in the 28-joint Disease Activity Score from baseline values. In Caucasians, the 1298 A (major) allele was associated with a significant increase in MTX-related adverse events characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an association between scores of MTX toxicity and the rs4846051 C allele, and haplotypes containing this allele, in African-Americans, but not in Caucasians. CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the rs4846051 C alleles were associated with MTX-related adverse events in Caucasians and African-Americans, respectively, but these findings should be replicated in larger studies. The rs4846051 SNP, which is far more common in African-Americans than in Caucasians, can also be proved to be a useful ancestry informative marker in future studies on genetic admixture.
16881357 [Activity of genetically programmed cell death of lymphocytes in rheumatoid arthritis]. 2006 AIM: To study activity of genetically programmed cell death (PCD) of lymphocytes in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Lymphocytes from 30 RA patients including 14 patients with RA history up to 2 years, and 12 healthy donors were studied for activity of caspase 4, 6, 8 usingfluorescence and caspase substrates 30, 60, 120, 150 and 180 min after start of the reaction and number of 1-2-thread serration of DNA with fluorescence of two DNA-tropic stains--EtBr and 4,6-DAPY Correlation was also studied between lymphocyte activity and RA activity, x-ray stage, duration, level of TNF-alpha. The trend in PCD activity of lymphocytes in immunosuppressive therapy was analysed. RESULTS: The activity of lymphocytic caspases in RA patients was low compared to healthy donors. A negative correlation was found between RA activity and activity of caspase 8 and 6. In RA therapy with methotrexate, sulphasalasine, glucocorticosteroids the activity of caspases and number of 1-thread serrations of DNA were subnormal. CONCLUSION: RA is associated with lymphocyte PCD disorders which may be involved in RA pathogenesis, in formation of clones of potentially autoaggressive lymphocytes, in particular. This process is not normalized by current methods of RA treatment causing unsatisfactory outcomes of RA therapy.
16920048 Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimm 2006 Dec We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.
18084704 Early rheumatoid arthritis in a patient with Sjögren's syndrome and pulmonary nodular amy 2007 Infliximab, an anti-tumor necrosis factor alpha antibody, is among the most effective therapies for rheumatoid arthritis (RA). In this study, we report a patient with early RA of 6 months who has Sjögren's syndrome and pulmonary nodular lesions concomitantly. The patient did not respond to methotrexate (MTX, 6;Smg per week) for 3 months. When introduction of infliximab therapy is considered, we need to exclude the possibility of pulmonary granulomatous infection and malignancy. With the use of computed tomography-guided percutaneous needle biopsy and subsequent histological examinations, this case was rapidly and confidently diagnosed as localized pulmonary nodular amyloidosis. Immunochemical staining showed light chain type nodular amyloidosis by a deposition of immunoglobulin kappa light chains, which is a rare condition in a patient with Sjögren's syndrome. We started combination therapy of infliximab (200;Smg per infusion) and MTX (6;Smg per week). Because of severe systemic eruption, this therapy was stopped halfway through the third infusion of infliximab, and MTX monotherapy was continued. Despite the withdrawal of infliximab therapy, the C-reactive protein values were decreased to an undetectable level at week 14, and the disease activity score for 28 joints was 3.1 at week 22. Clinical remission has been maintained more than 14 months with MTX alone. Infliximab has been used only for patients with recalcitrant RA, because the cost of its lifelong use would be an economic burden in most cases. An optimal and affordable strategy for the treatment of early RA should be developed. Our findings may support the idea that the combination therapy of infliximab and MTX for early RA alters the course of the disease.
17109060 Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year p 2007 Jul The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.
16249224 Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory poly 2006 May OBJECTIVE: To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment. DESIGN: Prospective cohort study. METHODS: 2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history. RESULTS: There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6). CONCLUSIONS: There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.
17965559 Methylenetetrahydrofolate reductase and reduced folate carrier-1 genotypes and methotrexat 2007 Oct We investigated the genotypes of methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier-1 (RFC-1), and the serum concentrations of methotrexate (MTX) in 100 outpatients with rheumatoid arthritis (RA). Frequencies of MTHFR C677T and A1298C were similar to those reported in Japanese RA patients, while frequencies of RFC-1 G80A genotypes differed from those reported in RA patients in the United States. No correlations were found between these genotypes and serum MTX levels.
17867299 [Transient leukemoid reaction of plasma cells in a patient with rheumatoid arthritis]. 2007 Aug A 69-year-old female with rheumatoid arthritis was admitted to our hospital with facial flushing and cervical lymphadenopathy on Jan, 2006. She had been treated with methotrexate (MTX), sulfasalazine (SSA) and prednisolone. The MTX and SSA were discontinued because of appetite loss just before admission. The patient's white blood cell count was 30100/microl with 32.5% of plasma cells, and 25.7% of plasma cells were observed in the bone marrow. Immunoelectrophoresis revealed polyclonal hypergammaglobulinemia on admission. Flow cytometry analysis revealed that the plasma cells in the bone marrow expressed CD38 and CD19 and did not express CD56. The lymphadenopathy and the increase of plasma cells in the peripheral blood and the bone marrow gradually decreased after the cessation of MTX and SSA.
18173925 Delayed neutrophil apoptosis in very early rheumatoid arthritis patients is abrogated by m 2007 Nov OBJECTIVES: To analyse the activation state and apoptosis of circulating neutrophils in untreated very early rheumatoid arthritis (VERA) and after exposure to low dose corticosteroids and methotrexate (MTX). METHODS: Neutrophils were isolated from the peripheral blood of VERA patients at 3 different times: before any treatment was started, 2 weeks after starting a low dose of prednisone (5-10 mg) and 4 months after reaching more than 20mg/week of MTX. The expression of different activation markers (CD11b, CD64, CD86 and CD69) in freshly isolated neutrophils was analysed by flow cytometry. Apoptosis was measured by the loss of DNA content, which was analysed by flow cytometry using propidium iodide. RESULTS: Compared to neutrophils from healthy controls, we have found a delayed neutrophil apoptosis within 6 h and 22 h of cultured polymorphonuclear leukocytes (PMN) derived from VERA patients without any treatment or treated with corticosteroids. The delay of PMN apoptosis was restored to control levels after treatment with MTX. CONCLUSION: The treatment of VERA patients with corticosteroids did not affect the delay of neutrophil apoptosis. However, delayed apoptosis was restored to control levels after treatment with low dose MTX, which highlights the importance of early RA treatment with MTX.
16443552 Reversible Epstein-Barr virus-negative lymphadenopathy and bone marrow involved by Hodgkin 2006 Jan We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative methotrexate-associated lymphadenopathy occurring with Hodgkin's lymphoma in the bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years of treatment with low-dose methotrexate, the patient developed pancytopenia, hypercalcemia, and elevated levels of liver enzymes over the course of 2 months. A computed tomography scan of the abdomen revealed splenomegaly and enlarged abdominal lymph nodes. A bone marrow biopsy demonstrated cellular marrow with 2 paratrabecular granuloma-like lesions composed of histiocytes, fibroblasts, small lymphocytes, a few plasma cells, and scattered CD30(+)CD15(+) Hodgkin's cells, including a classic Reed-Sternberg cell. The results of EBV studies of the bone marrow were negative. Within a month from withdrawal of methotrexate treatment, the patient's symptoms and the abnormalities in the laboratory results had regressed completely. A positron emission tomography scan failed to detect lymphadenopathy. Twelve months later, the patient remains free of symptoms.
17404485 [Inhibition of the joint destruction in RA by TNF-blocking agents]. 2007 Apr Tumor necrosis factor (TNF) -inhibitory biological response modifiers include neutralizing antibodies and receptor-immunoglobulin G (IgG) fusion proteins. These agents induce an amelioration of clinical signs and symptoms in most of the patients within a few weeks. Moreover, their inhibitory, or often repairing, effects on joint destruction are further excellent even in Japanese patients receiving a relatively lower dose of methotrexate (MTX) probably due to the direct inhibition of osteoclast activation through TNF.