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ID PMID Title PublicationDate abstract
23073309 Treat-to-target: measures. 2012 Jul Current approach to rheumatoid arthritis (RA) treatment combines early and aggressive therapy, with methotrexate as the anchor medication and monitoring disease activity to achieve the best possible outcome for patients. To recognise which patients are responding treatment and reaching low disease activity levels or remission, an objective outcome measure needs to be utilised in routine clinical care. DAS28, SDAI, CDAI and RAPID3 are all validated and similarly functioning measures that can be of use in everyday care, allowing rheumatologists to treat-to-target. The main challenge remains getting all rheumatologists to start using one of these measures as part of the care they provide.
21898074 Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: ret 2012 Jun We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice.
22127691 Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced 2011 Dec OBJECTIVE: Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. METHODS: The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. RESULTS: The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. CONCLUSION: The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab compared with placebo was also clinically meaningful in the biomarker-negative population.
21885199 Is rheumatoid arthritis a risk factor for oral bisphosphonate-induced osteonecrosis of the 2011 Nov Bisphosphonate-related osteonecrosis of the jaws is a relevant side-effect of these drugs that has been generating a great concern through increasing reports, worldwide, of this bone necrosis. Among several BRONJ hypothetical co-factors that could play a role in BRONJ pathogenesis, rheumatoid arthritis (RA) has been included as a relevant risk factor for BRONJ; however, until now the relationship between these diseases has not been fully explained. Thus, the purpose of this paper is to establish hypothetical factors that could link these two diseases, considering mainly inflammatory components and the organism effects of medicines used to treat RA, particularly steroids and methotrexate (MTX).
21485024 RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response crite 2011 Aug OBJECTIVE: To compare categories for activity/severity according to the Disease Activity Score 28-joint count (DAS28), the Clinical Disease Activity Index (CDAI), and the Routine Assessment of Patient Index Data 3 (RAPID3), an index without formal joint counts calculated in 5 versus >100 seconds, as well as the European League Against Rheumatism (EULAR)- DAS28 and the RAPID3 response criteria, in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID 1) clinical trial of certolizumab pegol (CZP). METHODS: Post hoc analyses were performed using correlations, cross-tabulations, and kappa statistics. Patients (treated with CZP plus methotrexate [MTX] or placebo plus MTX) were classified at baseline and at 52 weeks as high, moderate, low activity/severity or remission, according to the DAS28 (>5.1, >3.2 to ≤5.1, 2.6 to ≤3.2, <2.6 [total range 0-10]), the CDAI (>22, >10 to ≤22, >2.8 to ≤10, ≤2.8 [total range 0-76]), and RAPID3 (>12, >6 to ≤12, >3 to ≤6, ≤3 [total range 0-30]), as well as for good, moderate, and poor EULAR-DAS28 and proposed RAPID3 response criteria. RESULTS: All measures were correlated significantly: RAPID3 with DAS28 and CDAI (rho > 0.7), higher than erythrocyte sedimentation rate with C-reactive protein level (rho = 0.47). At 52 weeks, DAS28, CDAI, and RAPID3 low activity/remission was seen in 30%, 44%, and 42% of CZP-treated patients versus 3%, 7%, and 10% of control patients. Good, moderate, and poor EULAR-DAS28 responses were seen in 30%, 51%, and 19% of CZP-treated patients versus 3%, 28%, and 70% of control patients, and for RAPID3 in 39%, 30%, and 32% of CZP-treated patients versus 8%, 16%, and 76% of control patients. Kappa and weighted kappa values ranged from 0.36-0.53, indicating fair to moderate agreement. CONCLUSION: RAPID3, DAS28, and CDAI give similar results to distinguish CZP patients from controls in the RAPID 1 clinical trial. DAS28 is specific for clinical trials; RAPID3 appears pragmatically useful for usual care.
22083611 Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthr 2012 Nov The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis.
22018187 A dose of only 5 mg prednisolone daily retards radiographic progression in early rheumatoi 2011 Sep Glucocorticoids (GC) have been used to treat rheumatoid arthritis (RA) for more than 60 years. Despite this very long experience, there remains considerable debate concerning the adequate dosing and timing of these medications, primarily because of frequent and sometimes serious side effects, particularly in high doses. GCs are documented to provide immediate symptomatic relief and to decrease signs of inflammation in active disease. At the time when the Low-Dose Prednisolone Trial (LDPT) was designed, no clear evidence was available concerning whether low doses of GCs given over a long period add to slowing of structural damage in RA. The trial was therefore designed to test the hypothesis that even a low dose of prednisolone that was thought to cause no or only very limited harm could slow radiographic progression. The trial therefore included patients with active early RA (disease duration less than two years) who received either prednisolone 5 mg/day or placebo on concomitant DMARD therapy with parenteral gold or methotrexate for two years. Radiographs of hands and feet were taken at baseline, and at 6, 12 and 24 months. Structural damage was assessed using change in the Ratingen score (0-190 scale) as the primary outcome, and change in the Sharp/van der Heijde score (0-448 scale) for additional information concerning the same radiographs. Of 192 patients in the study, 166 were available for intention to treat analysis (ITT), and 76 completed the study per protocol (PP). Progression of the Ratingen score was significantly less at all consecutive time points in the prednisolone group compared to the control group, with the greatest difference after 6 months. At 24 months the increase in score in the prednisolone group was 1.2 ± 3.5, (95% CI 0.4-2.1) and in the placebo group 4.3 ± 6.8 (95% CI 2.7-5.9) (p=0.006, ITT-analysis). This was confirmed by the results of the Sharp/van der Heijde erosion and total score with an increase of the total score of 5.3 ± 10.7 units in the prednisolone compared to 11.4 ± 19.1 in the placebo group (p=0.022) at 24 months. The LDPT trial therefore confirmed that a very low daily dose of 5 mg prednisolone given over two years in combination with background DMARD therapy substantially decreases radiographically detectable damage in patients with early RA.
21412604 Potential drug interactions in patients with rheumatoid arthritis. 2011 Jan INTRODUCTION: The term polypharmacy, meaning the concomitant use of multiple medications by one individual, has been widely reported in institutionalized or elderly patients. It can, however, occur in patients with chronic diseases, such as rheumatoid arthritis (RA). OBJECTIVE: To quantify polypharmacy in a group of RA patients and to assess the risk of potential undesirable interactions between medications used for managing RA and those used for non-chronic diseases. METHODS: A cohort study was carried out with 103 RA patients registered at the Strategy of Access to Medications from the Brazilian Health Ministry, at the School of Pharmacy of the city of Florianópolis, state of Santa Catarina. Patients were monthly followed up by use of form completion. Drug interactions were identified by use of the Drugdex System - Thomson Micromedex® - Interactions database. RESULTS: Polypharmacy was found in 95.1% of the patients, and 19 potential undesirable interactions were observed between the drugs used by 74 patients (mean of 3.0 ± 1.2 interactions/patient). All potential interactions were related to methotrexate. Omeprazole was the major representative, accounting for 29.3% of the interactions, followed by diclofenac sodium (17.6%), and metamizole sodium (13.2%). CONCLUSION: Considering that this study confirms that polypharmacy is a common therapeutic practice in RA patients, it is worth emphasizing the need for greater surveillance regarding the adverse effects or effectiveness reduction of certain drugs due to drug interaction.
21502696 [The importance of pharmacogenetic tests in evaluation of the effectiveness of methotrexat 2011 Mar 30 Methotrexate (MTX) is still the gold standard in the treatment of rheumatoid arthritis and is used worldwide in more than 0.5 million patients with RA. Much hope is currently associated with the individualization of therapy provided to RA patients. The search is underway for biochemical and clinical markers that would be useful in predicting good response to MTX therapy. Along with clinical factors, genetic predisposition may also be helpful. Polymorphism of genes participating in MTX metabolism may affect the drug’s efficacy and the rate of adverse effects. Pharmacogenetic studies may contribute to more effective individualization of therapy for RA patients. There are many potential enzymes and transport proteins present in polymorphic forms, which are involved in transport of MTX into the cell, its metabolism and elimination from the cell. There is a chance that in the future through individualized therapy we will be able to customize therapy (type of drug, dose, route of administration) to the molecular subtype of the disease and the genotype of the patient. Patients with a specific type of polymorphism would require more frequent monitoring of the efficacy and safety of treatment. Note, however, that genetic predisposition is only one of the factors contributing to differences in pharmacotherapy in individual patients.
20726683 Trends in treatment strategies and the usage of different disease-modifying anti-rheumatic 2011 Jan OBJECTIVES: To determine which disease-modifying anti-rheumatic drugs (DMARDs) are currently used by Finnish rheumatologists to treat early rheumatoid arthritis (RA). METHODS: Information on sex, date of birth, and date of special medicine reimbursement decision for all new RA patients was collected from a nationwide register maintained by the Social Insurance Institution (SII) during the time period from 1 January 2000 to 31 December 2007. Patient cohorts were registered in 2-year time periods (2000-01, 2002-03, 2004-05, 2006-07) and DMARDs purchased by the patient cohorts during the first year after the date of reimbursement decision for RA were registered. The frequencies of early drug treatment strategies (combination of DMARDs, single DMARD, or no DMARDs) were evaluated. RESULTS: A total of 14 878 (68.0% female, 62.6% rheumatoid factor (RF)-positive) patients were identified. Between 2000 and 2001 the most commonly used treatment strategy for early RA during the first 3 months was single DMARD treatment (56.1%) and the most commonly used DMARD during the first year was sulfasalazine (63.0%), while between 2006 and 2007 the respective treatments were combination DMARDs (55.3%) and methotrexate (69.0%). The change in treatment strategies as well as in DMARDs used was highly significant (p < 0.001 for linearity). At the end of the study period only 4.9% of the patients with early RA were not receiving DMARDs during the first 3 months. CONCLUSIONS: Currently, combination therapy including methotrexate is the most commonly prescribed treatment strategy for early RA in Finland. In recent years, an increasing number of active drug treatments have been taken into practice.
23164197 Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients fr 2012 Nov 19 INTRODUCTION: Early rheumatoid arthritis (RA) patients may show rapid radiographic progression (RRP) despite rapid initiation of synthetic disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a matrix to predict risk of RRP despite early DMARD initiation in real life settings. METHODS: The ESPOIR cohort included 813 patients from the community with early arthritis for < 6 months; 370 patients had early RA and had received methotrexate or leflunomide during the first year of follow-up. RRP was defined as an increase in the van der Heijde-modified Sharp score (vSHS) ≥ 5 points at 1 year. Determinants of RRP were examined first by bivariate analysis, then multivariate stepwise logistic regression analysis. A visual matrix model was then developed to predict RRP in terms of patient baseline characteristics. RESULTS: We analyzed data for 370 patients. The mean Disease Activity Score in 28 joints was 5.4 ± 1.2, 18.1% of patients had typical RA erosion on radiographs and 86.4% satisfied the 2010 criteria of the American College of Rheumatology/European League Against Rheumatism. During the first year, mean change in vSHS was 1.6 ± 5.5, and 41 patients (11.1%) showed RRP. A multivariate logistic regression model enabled the development of a matrix predicting RRP in terms of baseline swollen joint count, C-reactive protein level, anti-citrullinated peptide antibodies status, and erosions seen on radiography for patients with early RA who received DMARDs. CONCLUSIONS: The ESPOIR matrix may be a useful clinical practice tool to identify patients with early RA at high risk of RRP despite early DMARD initiation.
22121130 Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of i 2012 May BACKGROUND: Treatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i. OBJECTIVES: To evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity. METHODS: A random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHE trial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal-Wallis). RESULTS: Baseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29 ± 0.96; placebo: 0.90 ± 1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26-0.28, p=0.002-0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2 ± 0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2 ± 2.2 vs 0.4 ± 1.2; p=0.0009). CONCLUSIONS: IL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.
22472929 Portuguese guidelines for the use of biological agents in rheumatoid arthritis - October 2 2011 Oct The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of nonresponders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 despite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res­ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist’s clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).
21962187 Methotrexate-induced cutaneous ulcers in a nonpsoriatic patient: case report and review of 2011 Sep BACKGROUND: Methotrexate is a mainstay of treatment for autoimmune conditions such as rheumatoid arthritis and psoriasis. Methotrexate has numerous potential side effects and, in rare circumstances, can lead to cutaneous ulceration. Methotrexate can cause skin ulceration, and stopping this medication can lead to complete healing of the ulcerated lesion. OBSERVATIONS: A 67-year-old man with rheumatoid arthritis on long-term methotrexate therapy presented to hospital with ulcers on his hands, elbows, and lower extremities. He had no history of psoriasis. Shortly after admission, the patient was noted to have pancytopenia. A bone marrow biopsy showed a hypocellular marrow. Both the cutaneous ulcers and the hypocellular marrow were thought to be induced by methotrexate. The ulcerated areas were biopsied, and histopathology showed no evidence of vasculitis. After 1 month of rehabilitative skin care, the patient's ulcers healed almost completely and his bone marrow suppression recovered. CONCLUSION: We report the fifth case of methotrexate-induced cutaneous ulceration in a nonpsoriatic patient and review the literature on this unusual drug reaction. Methotrexate can induce cutaneous ulceration in nonpsoriatic patients and should be considered a potential cause of ulceration in patients treated with this antimitotic agent.
22975732 Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadeq 2013 Jul OBJECTIVES: We aimed to assess the efficacy of tacrolimus (TAC) as an add-on therapy in patients with rheumatoid arthritis (RA) who were previously treated with methotrexate (MTX) but not with biologics. METHODS: The study group (MTX + TAC group) consisted of 157 patients (selected from among the patients in the Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005 to October 2009) who received add-on therapy with TAC in addition to MTX, but without biologics. A propensity score (PS) for the use of TAC was derived, and 471 PS-matched patients who received MTX alone or MTX with other non-biologic disease-modifying antirheumatic drugs (except for TAC), but not with biologics, were selected and served as the control group. Changes in disease activity in the two groups during three consecutive IORRA phases were analyzed by adjusting for confounding factors. RESULTS: The median 28-joint disease activity score (DAS28) decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the control group. After adjusting for confounding factors, the decrease in the DAS28 score in the MTX + TAC group was significantly larger (by 0.273 points) than that in the control group (P < 0.05). CONCLUSION: This study demonstrated the efficacy of add-on therapy with TAC to MTX in patients with RA in daily practice.
22390545 Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate 2012 Mar 5 INTRODUCTION: Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade. METHODS: Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and correlated with anticitrullinated peptide antibody (ACPA) status and clinical response as assessed by 28-joint Disease Activity Score utilizing C-reactive peptide and European League Against Rheumatism response criteria. RESULTS: RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman's ρ = 0.31 to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not predictive of clinical response. Changes in sG0/G1 were similar in the MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1. CONCLUSIONS: Baseline serum N-glycan hypogalactosylation, an index previously correlated with hypogalactosylation of IgG N-glycans, did not distinguish patients with rheumatoid arthritis who were likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement was associated with partial glycan normalization. ACPA-positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.
22887851 Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with r 2012 Dec OBJECTIVES: We assessed the influence of tocilizumab (TCZ), a humanised monoclonal anti-interleukin-6 receptor antibody, on antibody response following influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: A total of 194 RA patients received inactive trivalent influenza vaccination (A/H1N1, A/H3N2 and B/B1 strains). All patients were classified into the TCZ (n=62), TCZ+methotrexate (MTX) (n=49), MTX (n=65) and RA control (n=18) groups. Antibody titres were measured before and 4-6 weeks after vaccination using the haemagglutination inhibitory assay. RESULTS: For the A/H1N1 and A/H3N2 strains, the TCZ and TCZ+MTX groups achieved fold increases of 9.9-14.5, postvaccination seroprotection rates greater than 70% and seroresponse rates greater than 40%. For the B/B1 strain, seroresponse rates were approximately 30%, but fold increases and seroprotection rates were 5.0-5.4 and greater than 70%, respectively, in these treatment groups. MTX had a negative impact on vaccination efficacy, but adequate responses for protection were nevertheless demonstrated in the MTX group. Neither severe adverse effects nor RA flares were observed. CONCLUSIONS: TCZ does not hamper antibody response to influenza vaccine in RA patients. Influenza vaccination is considered effective in protecting RA patients receiving TCZ therapy with or without MTX.
22368231 Fcγ receptor type IIIA polymorphism influences treatment outcomes in patients with rheuma 2012 Jun OBJECTIVE: To assess the association between a single nucleotide polymorphism in the gene of FCGR3A and the response to treatment with rituximab (RTX) in rheumatoid arthritis (RA). METHODS: SMART is a randomised open trial assessing two strategies of re-treatment in patients responding to 1 g infusion of RTX with methotrexate on days 1 and 15 after failure, intolerance or contraindication to tumour necrosis factor (TNF) blockers. Among the 224 patients included, 111 could be genotyped and were included in an ancillary study of SMART. Univariate and multivariate analyses adjusted on disease activity score on 28 joints were performed to assess whether FCGR3A-158V/F polymorphism was associated with European League Against Rheumatism response at week 24. RESULTS: Among the 111 patients, 90 (81%) were responders of whom 30 (27%) were good responders. V allele carriage was significantly associated with a higher response rate (91% of responders vs 70%, OR 4.6 (95% CI 1.5 to 13.6), p=0.006). These results were also confirmed in rheumatoid factor-positive patients (93% vs 74%, p=0.025). In multivariate analysis, V allele carriage was independently associated with response to RTX (OR 3.8 (95% CI 1.2 to 11.7), p=0.023). CONCLUSION: The 158V/F polymorphism of FCGR3A seems to influence the response to RTX in patients with RA after failure, intolerance or contraindication to TNF blockers.
22078698 [Efficacy and safety of abatacept in patients with rheumatoid arthritis and no prior treat 2011 Nov Abatacept (ABA) is a recombinant human fusion protein that blocks co-stimulation signals on T lymphocytes, impeding their activation. Randomized and controlled trials examining efficacy and safety have been performed with ABA combined with methotrexate (MTX), vs MTX monotherapy and vs infliximab (IFB) combined with MTX in patients with Rheumatoid Arthritis and who are naïve to biologic therapy. ABA has shown to be more effective than MTX and at least as effective as IFB+MTX, in terms of activity and clinical remission, physical function and reduction in radiological progression. Safety data at 7 years have shown that the drug is comparable to MTX in monotherapy and safer than the IFB+MTX combination, although infections still constitute the main risk when using ABA. This review summarizes the safety and efficacy data of the AIM, ATTEST, Phase IIb IM101-100 and AGREE trials.
21365318 Paracoccidioidomycosis induced by immunosuppressive drugs in a patient with rheumatoid art 2011 Jul Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, which is endemic in many regions of Latin America. We describe the case of a 60-year-old man from a region endemic for PCM who presented with a long history of left hip pain. He had been treated over the past 3 years with immunosuppressive drugs (methotrexate, leflunomide, and adalimumab) for rheumatoid arthritis (RA). A hip radiograph showed lytic bone lesions, and a chest radiograph showed an expansive excavated lesion in the left lung, suggestive of a lung cancer with bone metastases. A left hip joint biopsy was inconclusive, but histological analysis of a surgical lung biopsy specimen was consistent with P. brasiliensis infection. Treatment with intravenous amphotericin B (50 mg/day) and hydrocortisone (25 mg/day) was initiated. However, increasing hip pain resulted in the amputation of the left lower limb, and the analysis of the surgical specimen revealed a diagnosis of bone sarcoma. Postoperatively, the patient developed sepsis and died approximately 1 month later. To our knowledge, this is the first report of PCM in a patient with RA who had been treated with immunosuppressive drugs, in particular TNF-α blocking agents. The atypical presentation (left hip pain alone) emphasizes the importance of considering PCM in the differential diagnosis of patients with pulmonary lesions and osteolytic lesions who live in a region endemic for PCM. This case report also demonstrates that health professionals in these regions must pay close attention to patients receiving immunosuppressive drugs because of the possibility of reactivating quiescent P. brasiliensis lesions.