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ID PMID Title PublicationDate abstract
17332704 [Evidence of cartilaginous benefit of treatment with infliximab in rheumatoid arthritis us 2007 Feb Recently, it has become possible to measure the concentration of serum cartilage oligomeric matrix protein (COMP) in various arthritis, and it is expected to be a novel biomarker indicative of cartilage destruction. In this study, we evaluated the diagnostic effectiveness of serum COMP in rheumatic diseases and analyzed the inhibition of cartilage destruction in patients with rheumatoid arthritis who were prescribed with infliximab (IFX) for one year. The changes in the concentration of serum COMP and the joint narrow space of Sharp score (Delta Sharp-JNS) were evaluated. The level of serum COMP decreased from 23.04+/-7.14 U/l to 8.69+/-2.89 U/l (p<0.005) and improved Delta Sharp-JNS (-0.50+/-6.38 points). We believed that these results were influenced by the effects of methotrexate (MTX) that was prescribed together with IFX, and we analyzed the group that was administered only MTX therapy as a reference. However, the serum COMP concentration and Sharp-JNS in the MTX group did not decrease. The serological and radiological results revealed that IFX inhibited cartilage destruction, and it is possible that serum COMP is one of the novel biomarkers in RA patients treated with anti-tumor necrosis factor-alpha antibody therapy.
17977580 Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South E 2008 Jun OBJECTIVES: To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA). METHODS: We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)). CONCLUSIONS: The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.
17181921 Regulation of serum chemokines following infliximab therapy in patients with rheumatoid ar 2006 Sep OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62. RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.
17003175 Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflam 2006 Nov OBJECTIVES: Herpes zoster (HZ) is a common disorder that causes substantial pain and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA) and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was increased in RA and whether treatment contributed to the risk of HZ. METHODS: After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK patients by semi-annual questionnaires during 33 825 patient-years of follow-up. Predictors of HZ were determined by Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The annualized incidence rate per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2-18.1) in MSK, and did not differ significantly after adjustment for age and sex. HZ was predicted by impaired functional status, as measured by the Health Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)] in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR 4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2-1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were significant predictors of HZ. CONCLUSION: The incidence of HZ is increased in RA and MSK compared with population-based rates. However, the rate of HZ in RA is not increased compared with MSK. After adjustment for severity, various treatments, but not methotrexate or biologics, were risk factors for HZ.
17207378 Association of tumour necrosis factor a, b and c microsatellite polymorphisms with clinica 2006 Nov OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.
17934080 Optimal use of methotrexate: the advantages of tight control. 2007 Nov The CAMERA study shows that using methotrexate in a tight control setting might lead to considerable improvement in disease activity in early rheumatoid arthritis See linked article p 1443.
18351533 [Epitheliotrophic capacity of serum eye drops from healthy donors versus serum from immuno 2008 Mar BACKGROUND: Autologous serum has been advocated for the treatment of persistent corneal epithelial defects and other ocular surface disorders which may be a local manifestation of a systemic disease. Many of these underlying disorders are cytokine-mediated and require immunosuppressive therapy. The systemic disease and medication could potentially influence the epitheliotrophic capacity of serum eye drops. We compared the effect of serum from healthy and immunosuppressed donors in a human corneal epithelial cell culture model. METHODS: Serum was prepared under standardised conditions from full blood samples of 10 healthy donors and 10 patients suffering from rheumatoid arthritis. All patients were treated with prednisolone and methotrexate, one also with azathioprine. In these serum samples EGF, FGF, HGF, PDGF-AB, TGF-beta1, fibronectin, vitamin A and E as well as IL-6 were quantified by means of routine ELISA or HPLC technology. SV-40 immortalised human corneal keratinocytes were cultured in 96-well plates at 37 degrees C, 5 % CO (2) with a fully defined culture medium. At 30 % confluency the culture medium was substituted by one of the test preparations. Proliferation of cell cultures was quantified by means of a luminescence-based ATP assay in dose-response experiments. A colony dispersion assay was used to examine the effect on cell migration and differentiation was assessed by means of scanning electron microscopy. RESULTS: Serum from healthy donors differed from serum of immunosuppressed individuals suffering from rheumatoid arthritis only in that it contained significantly higher amounts of fibronectin and TGF-beta1. Support of proliferation, migration and differentiation of corneal epithelial cells was dose-dependent, but no significant difference was observed between the serum of the two different groups of donors. At a dilution of 25 % serum of healthy donors showed a significantly higher stimulation of migration than serum of immunosuppressed patients. CONCLUSION: The effect of serum on migration but not proliferation is affected by systemic diseases requiring immunosuppression. If an epithelial defect of a patient with rheumatoid arthritis does not respond to treatment with diluted autologous serum, undiluted serum should be tried since the positive effect of serum on cell migration is positively correlated with dose.
17006638 Galactosylation of IgG from rheumatoid arthritis (RA) patients--changes during therapy. 2006 Nov It is well documented that serum IgG from rheumatoid arthritis (RA) patients exhibits decreased galactosylation of its conservative N-glycans (Asn-297) in CH2 domains of the heavy chains; it has been shown that this agalactosylation is proportional to disease severity. In the present investigation we analyzed galactosylation of IgG derived from the patients using a modified ELISA-plate test, biosensor BIAcore and total sugar analysis (GC-MS). For ELISA and BIAcore the binding of IgG preparations, purified from the patients' sera, to two lectins: Ricinus communis (RCA-I) and Griffonia simplicifolia (GSL-II) was applied. Based on ELISA-plate test an agalactosylation factor (AF, a relative ratio of GSL-II/RCA-I binding) was calculated, which was proportional to actual disease severity. Repeated testing of several patients before and after treatment with methotrexate (MTX) alone or in combination with Remicade (a chimeric antibody anti-TNF-alpha) supplied results indicating an increase of IgG galactosylation during the treatment. This introductory observation suggests that IgG galactosylation may be an additional indicator of the RA patients' improvement.
18805724 Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis. 2008 Oct INTRODUCTION: Leflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. Although its overall safety profile is good, a few cases of toxic epidermal necrolysis have been reported. CASE REPORT: This 36-year-old woman had rheumatoid arthritis that proved refractory to sulfasalazine and methotrexate, which were used successively in combination with symptomatic drugs. Leflunomide was started. A maculopapular rash and a fever developed 2 weeks later. The skin lesions spread rapidly to most of the body, and ulcers of the ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout and prednisolone (60 mg/day) were given. The skin lesions healed over the next month. Punctate keratitis with keratinization of the cornea led to complete loss of vision. DISCUSSION: The main adverse effects of leflunomide consist of diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic skin reactions. A few cases of severe skin reactions such as toxic epidermal necrolysis have been reported. They require immediate discontinuation of the drug and a washout procedure to hasten drug elimination from the body. CONCLUSION: Close monitoring for severe skin reactions is in order when using leflunomide.
18713784 Effects of infliximab therapy on biological markers of synovium activity and cartilage bre 2009 Jul BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.
17096694 Investigation of the clinical effect of large volume leukocytapheresis on methotrexate-res 2006 Oct Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.
18457979 Severe atherosclerosis in rheumatoid arthritis and hyperhomocysteinemia: is there a link? 2008 Jul Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.
19093297 Interaction of genes from influx-metabolism-efflux pathway and their influence on methotre 2008 Dec OBJECTIVE: Methotrexate (MTX) is the drug of choice for rheumatoid arthritis (RA) but is effective only in around 60% of treated patients. Bioavailability of MTX may be a major determinant of response status and this may be governed by variations in MTX receptor and transporter genes and genes responsible for polyglutamation and deconjugation. We investigated the contribution of single nucleotide polymorphisms (SNPs) in RFC, FOLR1, FPGS, GGH and MDR1 genes to MTX response in RA patients from North India. METHODS: RA patients recruited using American College of Rheumatology criteria, were categorized into good and poor responders to MTX, based on disease activity score. A total of 17 SNPs from the above mentioned genes were genotyped and tested for association with MTX response using [chi]2 test; logistic regression along with clinical variables; and gene-gene interaction using multifactor dimensionality reduction (MDR). RESULTS: One novel synonymous SNP Ala324Ala (972 G > A) was identified in RFC gene. The CT genotype of C3435T in MDR1 gene conferred almost twice the risk of poor response [[chi]2 = 5.85, P = 0.01, odds ratio (95% confidence interval) = 1.97 (1.13-3.42)] and was retained in binary logistic regression [B = 0.66, P = 0.025, adjusted odds ratio (95% confidence interval) = 1.93(1.09-3.42)]. Significant interaction between SNPs in GGH and MDR1 genes seems promising. CONCLUSION: Interactions between genes coding for deconjugation and transporter seem to be important determinants of MTX response in RA but replication and functional studies would be confirmatory.
17213520 Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methyl 2006 Nov BACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. RESULTS: The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation. Forty two per cent (63/150) of the patients had C677T polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The baseline characteristics of the patients with or without polymorphism were comparable. The frequency of adverse events was not increased in patients with C677T polymorphism with 11 patients experiencing adverse events as compared to 19 in the group without polymorphism (of whom 4 and 7 patients respectively discontinued treatment). The C677T polymorphism was not associated with any difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation. Further studies need to be done to look at polymorphisms in other enzymes that may have association with MTX clinical efficacy and toxicity.
17444589 Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving inf 2007 May OBJECTIVE: We assessed whether the addition of anti-tumor necrosis factor (TNF) agent to methotrexate (MTX) therapy might alter the response of patients with rheumatoid arthritis (RA) to pneumococcal vaccination. METHODS: Seventy patients with early RA (n = 20, 36, and 14 in the infliximab 3 mg/kg plus MTX, infliximab 6 mg/kg plus MTX, and placebo plus MTX groups, respectively) were included in an analysis of patients enrolled in an ASPIRE substudy. Patients received 0.5 ml pneumococcal vaccine (Pneumovax) 34 weeks after initiation of study treatment; patient sera were collected 4 weeks later (week 38). Antibody responses were tested using enzyme immunoassay methods for reactivity to a panel of 12 serotypes of the pneumococcal vaccine. RESULTS: No significant difference in response to Pneumovax was observed between the infliximab plus MTX and placebo plus MTX groups. Roughly 80%-85% of patients responded to at least one serotype; however, only 20%-25% of patients in the different treatment groups responded to at least 6 different serotypes. Comparable proportions of patients in the 3 treatment groups responded to an increasing number (> or = 1 to > or = 6) of different serotypes. Patients < 45 years of age and those receiving oral corticosteroids generally appeared to respond better than those age 45 to 65 years and those not receiving oral corticosteroids. CONCLUSION: All treatment groups in this study had lower responses to vaccine than would be expected in the normal population. However, the addition of the anti-TNF agent infliximab to MTX therapy did not appear to affect the response of patients with RA to pneumococcal vaccination.
16385521 Ultrasonographic and radiographic results from a two-year controlled trial of immediate or 2006 Jan OBJECTIVE: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). METHODS: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. RESULTS: From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). CONCLUSION: The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.
15948014 Intra-articular methotrexate in the treatment of rheumatoid arthritis and psoriatic arthri 2006 Mar The aim of our study was to evaluate the effects of intra-articular methotrexate (MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or unique arthritic involvement of one knee, were treated with intra-articular injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte sedimentation rate (ESR). On the same days, an ultrasonographic examination of the involved knee was performed by two independent experienced operators. Synovial thickness in the suprapatellar bursa and the presence of joint effusion and Baker's cyst were assessed. An increase of the mean value of maximal knee flexion angle and a reduction of the mean values of ESR and VAS between T0, T9 and T17 were demonstrated. Ultrasonographic evaluation showed significant reduction of synovial thickness and joint effusion. No differences were detected for the presence of Baker's cyst. We may conclude that repeated intra-articular injections of MTX resulted in a decrease of local as well as systemic inflammatory signs. As far as we know, this is the first study that explores the effects of intra-articular MTX in RA and PsA both clinically and by ultrasonography.
16652437 Adalimumab for treating rheumatoid arthritis. 2006 Jun OBJECTIVE: To assess the efficacy and safety of adalimumab in the treatment of rheumatoid arthritis (RA). METHODS: A Cochrane systematic review was performed. The literature search, selection and assessment of the methodological quality of the studies, and the data extraction were performed according to the standard methodology of the Cochrane reviews. Outcome measures included American College of Rheumatology (ACR) and European League Against Rheumatism responses, Disease Activity Score 28 and components of the ACR response, and radiographic and safety data. Weighted mean difference and relative risk were used for reporting continuous and dichotomous data, respectively. Number needed to treat (NNT) or to harm (NNH) were estimated when appropriate. When significant heterogeneity was not found, data were pooled. RESULTS: Six studies with 2,390 patients were included in this review. With adalimumab 40 mg every other week (eow) + methotrexate versus placebo + methotrexate, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 52 weeks were 35%, 32%, and 19% with NNT of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg eow and 20 mg every week (ew) significantly slowed the radiological progression. With adalimumab 40 mg eow versus placebo, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 24/26 weeks were 23.64%, 15.31%, and 12.22% with NNT of 5.0, 7.0, and 9.0, respectively. In most of the analyzed studies and comparisons, there were no significant differences in safety outcomes between adalimumab and control groups. CONCLUSION: On the basis of studies reviewed here, adalimumab is efficacious in the treatment of RA. No serious adverse effects occurred.
17137624 Simultaneous diagnosis of CD3+ T-cell large granular lymphocyte leukaemia and true thymic 2007 Jul CD3+ T-cell large granular lymphocyte (LGL) leukaemia is a mature T-cell neoplasm of cytotoxic T-lymphocytes. Neutropenia represents the most frequent peripheral blood cytopenia associated with CD3+ T-cell LGL leukaemia. A wide variety of diseases associated with LGL leukaemia have been reported, both autoimmune and neoplastic. We describe for the first time the association of true thymic hyperplasia with CD3+ T-cell line LGL leukaemia. The patient presented with severe symptomatic neutropenia. Complete and persistent haematological and molecular remission was induced with an association of low-dose methotrexate and cyclosporin A, followed by thymectomy.
18299492 Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. 2008 Feb 25 BACKGROUND: Rheumatoid arthritis is a severe inflammatory polyarthritis that requires long-term treatment with disease-modifying antirheumatic drugs. There is increasing concern about the influence of rheumatoid arthritis therapy on the risk for hematologic malignant neoplasms. METHODS: We used a case-control design nested in a cohort of 23,810 patients with rheumatoid arthritis assembled from administrative databases covering the population of Quebec, Canada. The study was carried out from January 1, 1980, through December 31, 2003. Case patients having hematologic malignant neoplasms were ascertained from physician billing and hospitalization records; each case patient was matched for age and sex with 10 control subjects. Adjusting for clinical variables and concomitant medications, we used conditional logistic regression to analyze potential associations between disease-modifying antirheumatic drug exposures and risk for hematologic malignant neoplasms. We estimated rate ratios attributable to each disease-modifying antirheumatic drug exposure. RESULTS: During the study, hematologic malignant neoplasms developed in 619 patients, including lymphomas in 346 patients, leukemia in 178 patients, and multiple myelomas in 95 patients. The unadjusted rate ratios for hematologic malignant neoplasms after drug exposures were as follows: methotrexate, 1.18 (95% confidence interval [CI], 0.99-1.40); azathioprine, 1.44 (95% CI, 1.01-2.03); and cyclophosphamide, 2.21 (95% CI, 1.52-3.20). Because biologic agents first appeared in the Régie d'Assurance Maladie du Quebec formulary in 2002, there were few exposures to these drugs. Adjusted estimates suggested that hematologic cancer risk was most elevated after exposure to cyclophosphamide (rate ratio, 1.84; 95% CI, 1.24-2.73). For lymphomas only, the adjusted rate ratio after cyclophosphamide exposure was 2.12 (95% CI, 1.33-3.54). CONCLUSIONS: In this large cohort of patients with rheumatoid arthritis, the greatest relative risk for hematologic malignant neoplasms was noted after use of cyclophosphamide. Assessments of risk related to newer and emerging therapies should carefully consider previous and concomitant medication exposures.