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ID PMID Title PublicationDate abstract
25501109 Clinical features and outcomes of 9 patients with immunodeficiency-associated lymphoprolif 2014 Immunodeficiency-associated lymphoproliferative disorders (LPD) represent a rare life-threatening clinical entity characterized by heterogeneous histological findings that range from polymorphic to monomorphic proliferated abnormal lymphocytes. Currently, there is no standard treatment for LPD. To elucidate the clinical features and treatment outcomes of immunodeficiency-associated LPD patients with rheumatoid arthritis (RA), we retrospectively evaluated 9 cases observed over a 5-year period. The diagnoses of these patients included 5 diffuse large B-cell lymphomas, 3 LPD, and 1 mucosa-associated lymphoid tissue lymphoma. At initial diagnosis, 6 patients had advanced-stage RA, and half of these underwent total knee arthroplasty. All patients with RA received methotrexate (MTX) and low-dose prednisolone. Biologics were administered to 4 of 9 patients. After the development of immunodeficiency-associated LPD, MTX discontinuation resulted in 5 complete remissions (CR), 1 partial remission, and 3 cases of stable disease. Relapse was observed in 3 of 5 CR patients in the MTX-withdrawal remission group. Subsequently, conventional chemotherapy, rituximab, and radiation were administered to 4, 3, and 1 patient, respectively. These treatments induced a second CR. In the chemotherapy group, 1 patient developed acute myocardial infarction and another experienced ileus and pulmonary abscess. In the rituximab group, no severe complications were observed. Consequently, all patients remained disease-free during the median 23-month follow-up period. Our results indicate that, depending on the RA disease stage, performance status, and extent of treatment response, less intensive treatments than those commonly indicated for non-Hodgkin lymphoma, involving MTX discontinuation and subsequent therapy containing rituximab, might be an efficient therapeutic strategy for immunodeficiency-associated LPD.
24654999 Certolizumab pegol in rheumatoid arthritis: current update. 2014 Jun INTRODUCTION: The development of TNF-α inhibitors (TNF-is) represents a major advancement in the treatment of rheumatoid arthritis (RA). Currently, there are five agents licensed for moderate-to-severely active RA. Certolizumab pegol (CZP) is a novel PEGylated, constant fragment-free TNF-i therapy, which is the focus of this review. AREAS COVERED: Data from Phase III randomised controlled trials in terms of clinical efficacy, radiographic progression, patient-reported outcomes and safety profile are reviewed. These include long-term data from open-label extension studies. EXPERT OPINION: The advantages of CZP include rapid reduction of disease activity, low rates of injection-site reaction and may be safe for use in pregnancy. The long-term data strengthen the position of CZP for use either as monotherapy or preferably in combination with disease modifying anti-rheumatic drugs (DMARDs), in moderate-to-severely active RA, comparable to other TNF-is. Notably, prolonged CZP exposure is not associated with increased risk of severe infection compared to general population, contrasting with preliminary analysis of short-term data. Over the next few years, evidence will be available on the use of CZP in combination with methotrexate for remission induction in DMARD-naïve patients, biomarkers and the development and licensing of TNF-i biosimilars.
24350725 SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Por 2014 Apr AIM: The aim of our study was to characterize the association of clinicopathological variables and the SLC19A1/RFC-1 G80A polymorphism in methotrexate (MTX)-related toxicity in Portuguese patients with rheumatoid arthritis. PATIENTS & METHODS: The study included 233 consecutively recruited patients with rheumatoid arthritis under MTX treatment. The SLC19A1 G80A polymorphism was evaluated by PCR-RFLP. RESULTS: Statistical analysis revealed that SLC19A1 80G carriers had increased risk of gastrointestinal toxicity (odds ratio [OR]: 2.61, p = 0.019) and that regular folic acid supplementation was associated with both overall and gastrointestinal toxicity protection (OR: 0.15, p < 0.001 and OR: 0.19, p < 0.001, respectively). Multivariate analysis confirmed the association of SLC19A1 80G and regular folic acid supplementation to gastrointestinal toxicity (OR: 5.53 and 0.13, respectively). Moreover, a multivariate Cox regression model demonstrated a higher risk of earlier gastrointestinal toxicity in SLC19A1 80G carriers (hazard ratio: 3.63, p = 0.002). CONCLUSION: SLC19A1 G80A genotyping may be a useful tool for clinicians to identify patients at higher risk for developing gastrointestinal toxicity related to MTX treatment.
23946436 The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammator 2014 Feb The management of RA, SpA, psoriasis and inflammatory bowel disease has significantly improved over the last decade with the addition of tumour necrosis factor inhibitors (anti-TNFs) to the therapeutic armamentarium. Immunogenicity in response to monoclonal antibody therapies (anti-drug antibodies) may give rise to low serum drug levels, loss of therapeutic response, poor drug survival and/or adverse events such as infusion reactions. To combat these, the use of concomitant MTX may attenuate the frequency of anti-drug antibodies in RA, SpA and Crohn's disease. Although a similar effect to methotrexate has been observed with AZA usage in the management of Crohn's disease, there is insufficient evidence to suggest that other DMARDs impact immunogenicity. In this article we review the evidence to date on the effect of immunomodulatory therapy when co-administered with anti-TNFs. We also discuss whether such a strategy should be employed in SpA and psoriasis, and if optimization of the MTX dose could improve biologic drug survival and thereby benefit disease management.
22915617 Association of joint space narrowing with impairment of physical function and work ability 2013 Jul OBJECTIVES: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. METHODS: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. RESULTS: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores. CONCLUSIONS: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.
24597620 Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in th 2014 Mar 5 BACKGROUND: The primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity. The objective of this study was to explore the association between clinical endpoints used to gauge RA treatment efficacy and patient-reported outcomes of health-related quality of life, fatigue, and physical function in RA patients treated with secukinumab in a phase 2 randomized controlled trial (RCT). METHOD: Adult RA patients (n = 237) with incomplete responses to methotrexate were randomized equally to receive monthly s.c. injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. Clinical endpoints used in this study included the ACR response criteria and its components and simplified disease activity score. Patient-reported outcomes (PRO) included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 [SF-36] Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Patients were categorized into mutually exclusive groups according to the magnitude and direction of change from baseline to week 16 in each clinical endpoint. Definitions of minimal important differences [MID] in each clinical endpoint were used to categorize patients, as well as thresholds beyond MID. Mean changes from baseline to week 16 were computed for each PRO and analyses of variance to test the differences in PRO changes observed across groups of patients that differed in each clinical endpoint. Analyses were limited to patients randomized to secukinumab treatment. All dose groups were combined (n = 187). RESULTS: Mean changes from baseline in each PRO differed significantly across groups of patients in the expected direction. With few exceptions, there was considerable agreement between clinical endpoints and PROs concerning the magnitude of change defined as clinically meaningful. More importantly, results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in HRQoL, fatigue, and physical function. CONCLUSION: Results of this study show considerable agreement between minimal thresholds of improvement established for PROs and clinical outcome measures used in RA treatment studies and provide thresholds to be considered in gauging the importance of a treatment effect that goes beyond what is considered as minimally important for PRO measures.
24449571 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. 2014 Jan OBJECTIVE: To investigate the global molecular effects of tocilizumab (TCZ) in comparison with methotrexate (MTX) treatment in synovial biopsy tissue obtained from patients with previously untreated rheumatoid arthritis (RA) before therapy (T0) and 12 weeks after the initiation of therapy (T12), and to compare the results with previous gene expression data obtained in synovial biopsy tissue from adalimumab (ADA)- and rituximab (RTX)-treated patients with RA. METHODS: Paired synovial biopsy samples were obtained at T0 and T12 from the affected knee of TCZ-treated RA patients and MTX-treated RA patients. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 microarrays, and confirmatory quantitative real-time reverse transcription-polymerase chain reaction experiments were performed on selected transcripts. The effects of TCZ and MTX on synovial cell populations and histologic characteristics were assessed by immunohistochemistry. RESULTS: Gene expression studies showed that blockade of the interleukin-6 receptor (IL-6R) gene (IL6R) using TCZ induced a significant decrease in the expression of numerous chemokine and T cell activation genes in the RA synovium. These effects strongly correlated with the molecular effects of MTX and RTX therapy on RA synovial tissue, but differed from the molecular changes induced by ADA (decreased expression of genes involved in cell proliferation). CONCLUSION: The molecular similarities between the effects of TCZ, RTX, and MTX therapies in the RA synovium indicate that B cell- and IL-6-dependent pathways play synergistic roles in the pathogenesis of the disease, in particular through activation of T cell responses. Moreover, these results open perspectives for the individualization of therapeutic decisions, based on a better knowledge of the synovial molecular effects of each type of RA therapy.
23899235 Lung involvement and drug-induced lung disease in patients with rheumatoid arthritis. 2013 Jul Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. Usual interstitial pneumonia and nonspecific interstitial pneumonia seem to be the most frequent patterns in RA patients with ILD, although the proportion of patients with usual interstitial pneumonia is higher than among patients with other systemic rheumatic autoimmune diseases. RA patients with ILD most frequently present with chronic symptoms of cough and dyspnea when climbing stairs or walking uphill. A physical examination may reveal inhalatory crackles and a pulmonary function test demonstrates restrictive physiology, often with reduced diffusing capacity. High-resolution computed tomography is generally sufficient to confirm a diagnosis of ILD, although a minority of cases may require a surgical lung biopsy. Conventional disease-modifying antirheumatic drugs such as methotrexate (MTX) or leflunomide (LEF) and biological agents such as TNF-blocking agents or rituximab may trigger or aggravate ILD in RA patients, and infections may contribute to increased mortality in such patients. LEF should not be used in patients with a history of MTX pneumonitis. The prevalence of interstitial pneumonia among RA patients treated with anti-TNF agents ranges from 0.5 to 3%; however, as the evidence that anti-TNF increases or decreases the risk of ILD is controversial, it is not clear whether this indicates more severe RA requiring biological therapy or the effect of exposure to potentially toxic drugs such as MTX or LEF. The development of treatment-related ILD is a paradoxical adverse event, and patients should be warned about this rare but serious complication of biological or disease-modifying antirheumatic drug therapy.
23415907 Reduced hepatotoxicity by total glucosides of paeony in combination treatment with lefluno 2013 Mar Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10 mg/week plus LEF 20 mg/day) with or without TGP for up to 24 weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p < 0.001) at 12 weeks. The proportion of patients whose ALT or AST levels were > 1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p < 0.05 respectively). More patients in the TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12 weeks, although there is no statistical significance. Similar results were observed at 24 weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA.
23773634 Potential food-drug interactions in patients with rheumatoid arthritis. 2013 Apr Various medications are used for the treatment of rheumatoid arthritis (RA). Food-drug interactions may occur with concomitant ingestion of particular food. For example, methotrexate (MTX), the anchor drug in the therapeutic strategy against RA, is an antifolate agent. Excessive presence or absence of dietary folic acid may regulate MTX metabolism, possibly leading to unexpected adverse reactions. In this review, we focus on MTX, isoniazide and calcineurin inhibitors, and the implications of potential food-drug reactions in rheumatology, suggesting the important role of nutritional evaluations in RA patients.
24687236 Efficacy and safety of certolizumab pegol in rheumatoid arthritis: meeting rheumatologists 2014 Apr Certolizumab pegol, a pegylated Fab' anti-tumour necrosis factor (TNF)-α agent, has shown efficacy in patients with rheumatoid arthritis (RA) unresponsive to previous treatment. In key randomised controlled trials involving patients with moderate to severe RA and an inadequate response to methotrexate or one or more disease-modifying antirheumatic drug (DMARD), the efficacy of certolizumab pegol, as monotherapy or with methotrexate, was similar to that reported in other anti-TNF clinical studies, with 60% or fewer of patients achieving American College of Rheumatology 20% improvement in RA. Rapid clinical response was also seen, with significant differences evident at week 1, and efficacy maintained at study end and in open-label extensions. Adding certolizumab pegol to non-biological DMARDs is efficacious in other RA populations. In the CERTAIN study, certolizumab increased remission rates, prevented disease worsening and improved work productivity and daily activity in patients with low to moderate RA. In the REALISTIC study, rapid and consistent clinical responses were observed in a diverse group of anti-TNF-eligible RA patients representing those seen in clinical practice. In the RAPID studies, rapid and sustained reduction in RA signs and symptoms, inhibition of structural joint damage progression, and improved physical function were seen with certolizumab pegol plus methotrexate versus methotrexate alone in RA patients with an incomplete response to methotrexate. Certolizumab pegol was generally well-tolerated in clinical trials, although long-term observational data are not yet available. Current data suggest that certolizumab pegol suits a 'treat to target' approach, providing rapid and sustained improvements in RA signs and symptoms, and beneficial effects on workplace and home productivity in patients with RA.
25433918 Methotrexate revisited: considerations for subcutaneous administration in RA. 2015 Feb Rheumatoid arthritis (RA) is associated with significant disability, morbidity, early mortality, and substantial financial burden. Despite newer antirheumatics, methotrexate (MTX) remains the most widely used disease-modifying antirheumatic drug. Subcutaneous (SC) MTX provides consistent, reliable delivery, with improved absorption and enhanced polyglutamization leading to increased response rates and fewer gastrointestinal side effects than oral MTX. Optimizing MTX with use of the SC formulation can improve outcomes and may delay or negate the need for costly biologics.
24288014 Discontinuation of adalimumab after achieving remission in patients with established rheum 2015 Feb OBJECTIVES: To investigate the possibility of discontinuing adalimumab (ADA) for 1 year without flaring (DAS28-erythrocyte sedimentation rate (ESR) ≥3.2), and to identify factors enabling established patients with rheumatoid arthritis (RA) to remain ADA-free. METHODS: Of 197 RA patients treated with ADA+methotrexate (MTX), 75 patients who met the ADA-free criteria (steroid-free and sustained DAS28-ESR remission for 6 months with stable MTX doses) were studied for 1 year. RESULTS: The mean disease duration and DAS28-ESR score in 75 patients was 7.5 years and 5.1 at baseline, respectively. The proportion of patients who sustained DAS28-ESR <2.6 (48%) and DAS28-ESR <3.2 (62%) for 1 year were significantly lower in the ADA discontinuation group than in the ADA continuation group; however, in patients with deep remission (DAS28-ESR ≤1.98) identified by receiver operating characteristics analysis following logistic analysis, these rates increased to 68% and 79%, respectively, with no significant difference between both groups. Remarkably, ADA readministration to patients with flare was effective in returning DAS28-ESR to <3.2 within 6 months in 90% and 9 months in 100% patients; among the patients who sustained DAS28-ESR <3.2 during ADA discontinuation, 100% remained in structural remission and 94% in functional remission. CONCLUSIONS: The possibility of remaining ADA-free for 1 year was demonstrated in established patients with RA with outcomes that ADA can be discontinued without flaring in 79% patients with deep remission, with similar rates in the ADA continuation group, and showed no functional or structural damage in patients with DAS28-ESR <3.2. ADA readministration to patients with flare during ADA discontinuation was effective.
23849101 Multi-modality imaging findings of methotrexate-related Epstein-Barr virus-associated hepa 2013 Sep Methotrexate (MTX)-associated lymphoproliferative disorders (MTX-LPDs) that occur in rheumatoid arthritis patients who were administered MTX for long periods are well known. However, studies on their pathology in forming hepatic tumors are rare. An approach using diagnostic imaging modalities, mainly computed tomography (CT), is considered a very useful tool for the differential diagnosis of various hepatic tumors. In the present study, detailed findings of dynamic CT, magnetic resonance (MR) imaging, and contrast-enhanced ultrasonography of a hepatic tumor that was confirmed as infected by Epstein-Barr virus, in a rheumatoid arthritis patient administered MTX are presented.
24629464 [The effect of alcohol and fatty foods on the P-alanine aminotransferase level in rheumato 2013 Dec 2 INTRODUCTION: The P-alanine aminotransferase level (P-ALAT) is used as a biomarker for drug-induced liver toxicity in rheumatic patients treated with methrotrexate and leflunomide. A rumour at Kong Christian X's Gigthospital states that P-ALAT analysed in the beginning of January should be taken with a pinch of salt due to an increased intake of fatty foods and alcohol through Christmas. MATERIAL AND METHODS: In a retrospective study of P-ALAT, performed on 133 patients diagnosed with either rheumatoid- or psoriatic arthritis (median age 62 years) the change in P-ALAT over Christmas was recorded along with medical treatment and disease activity. A total of 88 patients were included, while 45 were excluded due to disease activity or change of drug-dosage. RESULTS: P-ALAT increased significantly through Christmas. Treatment with methotrexate or leflunomide was not a significant explanatory variable but age was. Lower age predicted higher P-ALAT increase over Christmas. The changes in P-ALAT did not lead to changes in medical treatment. CONCLUSION: A statistical significant increase of P-ALAT was detected. This might be due to exaggerated consumption of fatty food and alcohol during Christmas or less likely due to heavy dancing around the Christmas tree. The increase of P-ALAT during Christmas is of no clinical significance. Although the rumor is true, there is no need for worries. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
24942466 Use of oral and subcutaneous methotrexate in rheumatoid arthritis patients in the United S 2014 Nov OBJECTIVE: To examine the patterns of methotrexate (MTX) use among rheumatoid arthritis (RA) patients. METHODS: Using data from RA patients enrolled in a US commercial health plan and the US Medicare program, we identified RA patients initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined as no gap for ≥90 days. RESULTS: New oral MTX users in Medicare (n = 20,431) were 76.9% women, had a mean ± SD age of 69.7 ± 11.7 years, and contributed a median followup of 2.6 years (interquartile range 1.7-3.5 years). Only 38% received dosages ≥20 mg/week at any time. Approximately 50% of patients discontinued MTX at 1 year, although more than one-third of patients subsequently restarted. New commercially insured oral MTX users (n = 4,048) were similar to Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX subsequently initiated a biologic agent, mostly anti-tumor necrosis factor (85%). Of these, only 50% received MTX at a dosage of ≥20 mg/week, and only 21% of individuals switched to SC MTX (4%) or received hydroxychloroquine (8%), sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially insured patients, 35% initiated a biologic agent, mostly anti-tumor necrosis factor therapies (90%). Of these, 43% never received MTX ≥20 mg/week. CONCLUSION: Titration to a higher-dose oral MTX and use of SC MTX among RA patients were infrequent and may have been underutilized. Further work to optimize MTX dosing before patients are switched to a biologic agent may be warranted.
23286772 Persistence of antibody response 1.5 years after vaccination using 7-valent pneumococcal c 2013 Jan 4 INTRODUCTION: The aim of this study was to explore the persistence of an antibody response 1.5 years after vaccination with 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA) treated with different antirheumatic drugs. METHODS: Of 505 patients initially recruited, data on current antirheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD, range) 1.4 (0.5; 1 to 2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed by using enzyme-linked immunosorbent assay (ELISA). Original treatment groups were as follows: (a) RA receiving methotrexate (MTX); (b) RA taking anti-TNF monotherapy; (c) RA taking anti-TNF+MTX; (d) SpA with anti-TNF monotherapy; (e) SpA taking anti-TNF+MTX; and (f) SpA taking NSAID/analgesics. Geometric mean levels (GMLs; 95% CI) and proportion (percentage) of patients with putative protective antibody levels≥1 mg/L for both serotypes, calculated in different treatment groups, were compared with results 4 to 6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed by using logistic regression analysis. RESULTS: Of 398 patients participating in the 1.5-year follow up, 302 patients (RA, 163, and SpA, 139) had unchanged medication. Compared with postvaccination levels at 1.5 years, GMLs for each serotype were significantly lower in all groups (P between 0.035 and <0.001; paired-sample t test), as were the proportions of patients with protective antibody levels for both serotypes (P<0.001; χ2 test). Higher prevaccination antibody levels for both serotypes 23F and 6B were associated with better persistence of protective antibodies (P<0.001). Compared with patients with protective antibody levels at 1.5 years, those not having protective antibody levels were older, more often women, had longer disease duration and higher HAQ and DAS, and had a lower proportion of initial responders to both serotypes. CONCLUSIONS: After initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly, reaching levels before vaccination in this cohort of patients with established arthritis treated with different antirheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. To boost antibody response, early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies. TRIAL REGISTRATION NUMBER: EudraCT EU 2007-006539-29 and NCT00828997.
25366268 Optimizing the expediency of TNFi in rheumatoid arthritis: offering a TNFi holiday in pati 2014 Dec INTRODUCTION: The treatment of rheumatoid arthritis (RA) has been revolutionized since the introduction of biological disease-modifying antirheumatic drugs such as tumour necrosis factor alpha inhibitors (TNFi), and clinical remission has become a realistic target in the treatment strategy. Discontinuation strategies of TNFi therapy after reaching sustained remission or low-disease activity (LDA) have been emerging. These strategies are important considering the risk-benefit profile of TNFi, as well as looking at them from a cost-economic point of view. AREAS COVERED: This article presents an overview of recent major studies on TNFi withdrawal, and tapering and about the safety of doing so. EXPERT OPINION: Although data are still limited, tapering or discontinuing TNFi in some RA patients may well be possible, especially in the early RA patients who are methotrexate naive. Also, a substantial group of longer established RA patients can stop or taper TNFi, particularly when ultrasonography signals are negative. However, before making the decision of implementing it in the routine care for RA patients, more predictors for successful discontinuation are desired.
24654994 A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in ou 2014 OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.
23292116 A review of therapeutic challenges and achievements of methotrexate delivery systems for t 2013 May PURPOSE: Methotrexate (MTX) is one of the most widely studied and effective therapeutics agents available to treat many solid tumors, hematologic malignancies, and autoimmune diseases such as rheumatoid arthritis; however, the poor pharmacokinetic and narrow safety margin of the drug limits the therapeutic outcomes of conventional drug delivery systems. For an improved delivery of MTX, several pathophysiological features such as angiogenesis, enhanced permeability and retention effects, acidosis, and expression of specific antigens and receptors can be used either as targets or as tools for drug delivery. METHODS: There are many novel delivery systems developed to improve the pitfalls of MTX therapy ranged from polymeric conjugates such as human serum albumin, liposomes, microspheres, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, polymeric micelles, in situ forming hydrogels, carrier erythrocyte, and nanotechnology-based vehicles such as carbon nanotubes, magnetic nanoparticles, and gold nanoparticles. Some are further modified with targeting ligands for active targeting purposes. RESULTS: Such delivery systems provide prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models. Nevertheless, more complementary studies are needed before they can be applied in human. CONCLUSION: This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle.