Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29387065 Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limi 2017 INTRODUCTION: An increased expression of interferon (IFN)-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA). However, some controversy exists concerning its clinical relevance. The main aim of this study is to evaluate whether quantitative and qualitative differences in the activation of the IFN pathway may account for these findings. METHODS: The expression of IFN-induced protein 44 (IFI44), IFN-induced protein 44 like (IFI44L), IFN alpha inducible protein 6, and MX dynamin-like GTPase 1 (MX1) was determined in peripheral blood in 98 RA patients (IFI6) and 28 controls. RA patients were classified into groups according to their clinical stage and treatments received: very early RA (VERA), biological disease-modifying antirheumatic drug (bDMARD) naive, and bDMARD. An additional group of 13 RA patients candidates for tumor necrosis factor alpha (TNFα) blockade was also recruited. The associations among IRGs were evaluated by network and principal component analyses. RESULTS: The expression of all IRGs was increased in RA to different levels. The IFN score was increased in all RA groups (VERA, bDMARD-naïve, and bDMARD), but important differences in their degree of activation and in the relationships among IRGs were observed. The IFN score correlated with the accumulated disease activity score 28-joints, and it was found to be a predictor of clinical outcome in VERA. No differences in the IFN score were observed between the bDMARD-naive and bDMARD groups, but opposite associations with the clinical parameters were noted. Interestingly, the correlations among IRGs delineate different pictures between these two groups. The IFN score at baseline predicted poor clinical outcome upon TNFα blockade. Although no absolute changes in the IFN score were found, TNFα-blockade shifted the associations among IRGs. CONCLUSION: A certain heterogeneity within the IFN signature can be recognized in RA, depending on the clinical stage. The structure of the IFN signature may be a potential explanation for the controversy in this field and must be considered to decipher its clinical relevancein RA.
29127246 Non-oncologic Applications of PET/CT and PET/MR in Musculoskeletal, Orthopedic, and Rheuma 2017 Nov 10 Positron Emission Tomography (PET) is often underutilized in the field of musculoskeletal imaging, with key reasons including the excellent performance of conventional musculoskeletal MRI, the limited spatial resolution of PET, and the lack of reimbursement for PET for non-oncologic musculoskeletal indications. However, with improvements in PET/CT and PET/MR imaging over the last decade as well as an increased understanding of the pathophysiology of musculoskeletal diseases, there is an emerging potential for PET as a primary or complementary modality in the management of rheumatologic and orthopedic patients. Specific advantages of PET include the convenience of whole body imaging in a single session, the relative resilience of the modality in the imaging of metallic implants compared to CT and MRI, the ability to evaluate deep joints not amenable to palpation, and the potential for improved specificity of diagnosis with novel radiopharmaceuticals. In this review, we discuss multiple radiopharmaceuticals and technical consideration of PET/CT and PET/MRI that can be employed in imaging of non-tumoral bone and soft tissue disorders. Both PET/CT and PET/MR hold significant promise in the field of musculoskeletal imaging, and with further radiopharmaceutical development and clinical research, these hybrid modalities can potentially transform the current management of patients with orthopedic and rheumatologic disease.
28923440 Interstitial lung disease in the connective tissue diseases; a paradigm shift in diagnosis 2018 Jan Interstitial lung disease (ILD) in the connective tissue diseases (CTD) is amongst the most challenging aspect of care of patients with rheumatic diseases and is the source of significant morbidity and mortality. While there has been progress in our understanding of the natural history of these complications, we still suffer from a limited reservoir of data to confidently determine which patients are at highest risk for disease and those who are at highest risk for disease progression. Treatment options until recently have been limited to anti-inflammatory therapies but with the emerging availability of anti-fibrotic therapies, a shift in strategy is emerging to target therapies based on the specific radiographic, histopathologic features and biomarker profiles that are unique to patients with rheumatic diseases and ILD.
28913818 A Spectroscopic Study of Interaction of Auricyanide with n-Acetylcysteine. 2018 Jun Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand n-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono- and di-n-acetylcysteine-substituted intermediates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with n-acetylcysteine through trans effect. At equimolar concentrations of auricyanide and n-acetylcysteine, only mono-substituted mixed-ligand complex was formed. Substitution of the data obtained to various kinetic models suggested that the reaction orders are 0.6 in terms of n-acetylcysteine, 1.5 in terms of auricyanide, and 2 overall. The intermediates detected in this work may help to synthesize more effective and less toxic gold drugs.
29189127 Biosimilars: From Extrapolation into Off Label Use. 2017 BACKGROUND: Biologic drugs have revolutionised the management of many inflammatory conditions. Patent expirations have stimulated development of highly similar but non-identical molecules, the biosimilars. Extrapolation of indications is a key concept in the development of biosimilars. However, this has been met with concerns around mechanisms of action, equivalence in efficacy and immunogenicity, which are reviewed in this article. METHODS: Narrative overview composed from literature search and the authors' experience. Literature search included Pubmed, Web of Science, and online document archives of the Food and Drug Administration and European Medicines Agency. RESULTS: The concepts of biosimilarity and extrapolation of indications are revisited. Concerns around extrapolation are exemplified using the biosimilar infliximab, CT-P13, focusing on mechanisms of action, immunogenicity and trial design. The opportunities and cautions for using biologics and biosimilars in unlicensed inflammatory conditions are reviewed. CONCLUSIONS: Biosimilars offer many potential opportunities in improving treatment access and increasing treatment options. The high cost associated with marketing approval means that many bio-originators may never become licenced for rarer inflammatory conditions, despite clinical efficacy. Biosimilars, with lower acquisition cost, may improve access for off-label use of biologics in the management of these patients. They may also provide opportunities to explore off-label treatment of conditions where biologic therapy is less established. However, this potential advantage must be balanced with the awareness that off-label prescribing can potentially expose patients to risky and ineffective treatments. Post-marketing surveillance is critical to developing long-term evidence to provide assurances on efficacy as well as safety.
28280299 A practical guide about biosimilar data for health care providers treating inflammatory di 2017 To make informed decisions about the safety, efficacy, and clinical utility of a biosimilar, health care providers should understand the types and be able to analyze data generated from a biosimilar development program. This article reviews the biosimilar guidelines, the biosimilar development process to provide education and context about biosimilarity, and uses examples from infliximab biosimilars to review the terminology and potential types of analyses that may be used to compare potential biosimilars to the originator biologic. A biosimilar is a biologic product that is highly similar to an approved (originator) biologic, notwithstanding minor differences in clinically inactive components, and with no clinically meaningful differences in terms of the safety, purity, and potency of the product. Due to their complex nature and production in living systems, it is not possible to exactly duplicate the approved originator biologic. To ensure biosimilars provide consistent, safe, and effective treatment comparable to the originator biologic, extensive analyses of the potential biosimilar are conducted, including side-by-side analytical, nonclinical, and clinical comparisons. A key goal is to determine whether there are sufficient relevant similarities in chemical composition, biologic activity, and pharmacokinetic aspects between the potential biosimilar and the originator. Regulatory approvals and marketing authorizations for biosimilars are made on a case-by-case and agency-by-agency basis after evaluating the totality of the evidence generated from the entire development program. Understanding how regulatory agencies review data for approval can help health care providers make appropriate decisions when biosimilars become available for use in the treatment of inflammatory diseases, and therefore they should review the literature to gain further information about specific biosimilars.
27590039 The toxicity of methotrexate in male fertility and paternal teratogenicity. 2017 Jan There is a high prevalence of methotrexate (MTX) use in males of reproductive age. The scope of this paper reviews what is known regarding risks to fertility and partners' pregnancy outcomes with regard to MTX use in men. Areas covered: This paper reviews the evidence for current recommendations for MTX use and male fertility and aims to educate professionals regarding MTX use in reproducing males so that patients may be counseled appropriately. A literature search included peer-reviewed sources from PubMed searches and the literature referenced within. Expert opinion: There is a lack of evidence regarding effects of MTX on male fertility. The recommendation to stop MTX three months prior to conception is safe, but is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity but rather the timeframe of spermatogenesis. Given the unclear evidence, patients treated with MTX must be counseled on the likelihood of adverse effects of MTX and role of sperm cryopreservation. Future studies are needed to help elucidate the unclear evidence of MTX effects on male fertility and pregnancy outcomes.
27623319 Review of the bioanalytical methods for the determination of methotrexate and its metaboli 2017 Jan Methotrexate is an old drug that has found use in several therapeutic areas, such as cancer to treat various malignancies, rheumatoid arthtritis and inflammatory bowel disease. Owing to its structural properties of possessing two carboxylic acid groups and having low native fluorescence, it has provided technical challenges for development of bioanalytical methods. Also, in vivo metabolism leading to circulatory metabolites such as 7-hydroxymethotrexate and 2,4-diamino N(10) -methylpteroic acid, as well as the formation of polyglutamate metabolites intracellularly have added further complexity for the assays in terms of the analytes that need to be quantified in addition to methotrexate. The present review is aimed at providing a concise tabular summary of chromatographic assays with respect to method nuances including assay/chromatographic conditions, key validation parameters and applicable remarks. Several case studies are reviewed under various subheadings to provide the challenges involved in the method development for methotrexate and metabolites. Finally, a discussion section is devoted to overall perspectives obtained from this review.
27659403 Alarmins firing arthritis: Helpful diagnostic tools and promising therapeutic targets. 2017 Jul Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat-shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout. Although formerly being linked to initiation and chronification of inflammatory arthritis, driving auto- and paracrine inflammatory loops, more recent research has also unraveled the alarmins' role in the crosstalk between innate and adaptive immunity and in resolution of inflammation. Providing a state-of-the-art overview of known alarmins, this review lists the known modes of action and pathologic contribution of alarmins to inflammatory arthritis, as well as biomarker potential of alarmins in the clinical setting for tracking disease severity. Based upon research on animal experimental models (CIA, AIA) and clinical trials, a look is made into potentially viable strategies for modifying alarmin secretion and their target receptor (e.g. TLR, RAGE) interaction with the purpose of attenuating arthritic disease.
27926664 Short article: Absence of serological rheumatoid arthritis biomarkers in inflammatory bowe 2017 Mar OBJECTIVE: Biomarkers that are associated with future progression to rheumatoid arthritis (RA) and joint destruction have been discovered previously in patients with arthralgia. The present study examined these RA biomarkers in inflammatory bowel disease (IBD) patients with arthropathies. PATIENTS AND METHODS: Sera from 155 IBD patients with and 99 IBD patients without arthropathies were analyzed for immunoglobulin (Ig) M rheumatoid factor (RF), IgA-RF, anti-cyclic citrullinated peptide 2, anti-cyclic citrullinated peptide 3.1, and anti-carbamylated protein antibody positivity using enzyme-linked immunosorbent assays. The prevalence of the autoantibodies in the IBD patients was compared with the prevalence in RA patients. RESULTS: No differences were found in biomarker positivity between IBD patients with and without arthropathies. Significantly more biomarker positivity (P<0.001) was observed in RA patients compared with IBD patients with arthropathies. Also, smoking turned out to be significantly associated with positivity for IgM-RF or IgA-RF. CONCLUSION: Our findings suggest that there is no apparent clinical value in the detection of RA biomarkers in serum of IBD patients to help identify arthropathies.
28511426 Effect of Anti-Cyclic Citrullinated Peptide and HLA-DRB1 Subtypes on Clinical Disease Acti 2017 Mar INTRODUCTION: Rheumatoid arthritis (RA) is a crippling disease with a global prevalence of approximately 0.5%-1% in adults. Genetic, environmental and immunologic factors contribute importantly to pathogenesis of RA. American College of Rheumatology (ACR) assists in early diagnosis of the disease. AIM: The aim of this study was to investigate the effects of HLA-DRB1 gene and anti-Cyclic Citrullinated Peptide (CCP) antibody on Clinical Disease Activity Index (CDAI) and to determine the frequency of HLA-DRB1 alleles in the patients with RA. MATERIALS AND METHODS: In this descriptive-analytical study, 64 patients with RA referring rheumatology clinic of Hajar Hospital, Shahr-e-Kord, Iran were enrolled based on ACR criteria (1987) by convenience sampling. All patients were examined to assess primary CDAI and referred to laboratory for serologic tests [Rheumatoid Factor (RF) and anti-CCP]. After the patients' DNA was extracted, HLA-DRB1 was determined per single specific primer-polymerase chain reaction by inno-train kits. The patients were re-examined six months later. RESULTS: The most prevalent type of HLA-DRB1 in the studied patients was 04. In patients with HLA-DRB1 (04), HLA-DRB1 (01), and HLA-DRB1 (15), CDAI decreased pronouncedly after six months, but in other patients it did not (p<0.05). Of the patients, 81.3% had high titers of anti-CCP, but no association between anti-CCP and CDAI was found. CONCLUSION: RA could be a multifactorial disease. The patients with HLA-DRB1 (04), HLA-DRB1 (01) and HLA-DRB1 (15) showed a good response to routine treatments. The patients with HLA-DRB1 (04) are likely to have no decrease in secondary CDAI. High titers of anti-CCP in patients may indicate the severity of RA in the studied region and perhaps environmental, genetic and unknown or idiopathic factors are aetiologically crucial.
28621153 Depression in primary Sjögren's syndrome: a systematic review and meta-analysis. 2018 Feb There is substantial uncertainty regarding the prevalence of depression in Primary Sjögren's syndrome (pSS). We conducted a systematic review aiming to evaluate the association of pSS with depression. PubMed, Web of Science, VIP, CNKI and Wanfang database were searched to find the published literatures (from these databases established to October 2016). Studies were screened according to inclusion and exclusion criteria and the qualities of included studies were evaluated. The data was analyzed using Revman5.2 software. A total of 12 studies including 1917 patients were eligible for inclusion in the systematic review and meta-analysis. In this meta-analysis, Severity of depression was assessed using psychometric measures, such as PHQ-9; HADS; CES-D; Zung depression scale and BDI. The result revealed that pSS was associated with an increased prevalence of depression (summary odds ratio (OR) = 5.36, 95% CI: 4.05-7.09, P < 0.01). The depression score in pSS patients (standardized mean difference (SMD) = 1.47, 95% CI: 0.81-2.12, P < 0.01) were higher than in the control group. Depression is highly prevalent in pSS than in healthy controls. Early recognition and appropriate intervention are therefore essential to reduce the negative impact of depression on the patient's quality of life and outcome of their disease.
28289872 Criteria sets for primary Sjogren's syndrome are not adequate for those presenting with ex 2017 May Patients with primary Sjogren's syndrome (pSS) may go undiagnosed or be misclassified due to the insidious nature and wide spectrum of the disease. The available several classification criteria emphasize glandular findings. We aimed to analyze the efficiency of various classification criteria sets in patients diagnosed on the clinical basis by expert opinion and to compare those pSS patients who fulfilled these criteria with those who did not. This is a multicenter study in which 834 patients from 22 university-based rheumatology clinics are included. Diagnosis of pSS was made on the clinical basis by the expert opinion. In this study, we only interviewed patients once and collected available data from the medical records. The European criteria, American-European Consensus Group (AECG) and American College of Rheumatology (ACR) Sjogren's criteria were applied. Majority of the patients were women (F/M was 20/1). The median duration from the first pSS-related symptom to diagnosis was significantly shorter in men (2.5 ± 2.3 vs 4.3 ± 5.9 years) (p = 0 < 0.016). When the European, AECG and ACR Sjogren's criteria were applied, 666 patients (79.9%) satisfied at least one of them. In total, 539 patients (64.4%) satisfied the European, 439 (52.6%) satisfied the AECG, and 359 (43%) satisfied the ACR criteria. Among the entire group, 250 patients (29.9%) satisfied all and 168 (20.1%) met none of the criteria. The rates of extraglandular organ involvements were not different between patients who met at least one of the criteria sets and those who met none. There is an urgent need for the modification of the pSS criteria sets to prevent exclusion of patients with extraglandular involvements as the dominant clinical features.
32104332 The role of serratiopeptidase in the resolution of inflammation. 2017 May Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II), a key enzyme associated with production of different inflammatory mediators including interleukins (IL), prostaglandins (PGs) and thromboxane (TXs) etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs) alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory) emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug. The study also illustrates a comparative analysis of conventional drugs and enzyme based therapeutic to combat inflammation.
27925370 The role of enjoyment in exercise for people with arthritis: Four different viewpoints fro 2017 Dec PURPOSE: There is limited research on the role of enjoyment of exercise among people with arthritis. The aim of the present study was to determine distinct viewpoints on exercise held by people with arthritis, and how enjoyment features in these viewpoints. METHODS: A Q-methodology study was conducted, which involved two interviews with people with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis (aged 20-85 years). In the first interviews, 11 participants helped to create the Q-set, a set of statements reflecting a range of existing views on exercising. In the second interviews, 12 participants (nine of the 11 from the first interviews and three others) ranked the Q-set on a forced quasi-normal distribution of agreement. A Q-method factor analysis was carried out to determine groupings of participants with similar views on exercise. RESULTS: Four groupings were discovered, and defined in terms of rankings of statements and illustrative quotes from the ranking procedure. The first grouping had all changed their exercise habits after diagnosis with arthritis. The second grouping had a shared enjoyment for walking to stay healthy. The third grouping's viewpoints focused on knowledge about how much exercise they should carry out. The fourth grouping shared a sense of importance of being responsible for their health by exercising. CONCLUSION: These findings provide information about the role that enjoyment plays in motivating people with arthritis to exercise, although enjoyment of exercise was not expressed by all participants. People with arthritis who share these viewpoints on exercise enjoyment may require different forms of advice regarding feasible and enjoyable exercise.
28280400 Telemedicine delivery of patient education in remote Ontario communities: feasibility of a 2017 OBJECTIVE: Telemedicine-based approaches to health care service delivery improve access to care. It was recognized that adults with inflammatory arthritis (IA) living in remote areas had limited access to patient education and could benefit from the 1-day Prescription for Education (RxEd) program. The program was delivered by extended role practitioners with advanced training in arthritis care. Normally offered at one urban center, RxEd was adapted for videoconference delivery through two educator development workshops that addressed telemedicine and adult education best practices. This study explores the feasibility of and participant satisfaction with telemedicine delivery of the RxEd program in remote communities. MATERIALS AND METHODS: Participants included adults with IA attending the RxEd program at one of six rural sites. They completed post-course program evaluations and follow-up interviews. Educators provided post-course feedback to identify program improvements that were later implemented. RESULTS: In total, 123 people (36 in-person and 87 remote, across 6 sites) participated, attending one of three RxEd sessions. Remote participants were satisfied with the quality of the video-conference (% agree/strongly agree): could hear the presenter (92.9%) and discussion between sites (82.4%); could see who was speaking at other remote sites (85.7%); could see the slides (95.3%); and interaction between sites adequately facilitated (94.0%). Educator and participant feedback were consistent. Suggested improvements included: use of two screens (speaker and slides); frontal camera angles; equal interaction with remote sites; and slide modifications to improve the readability on screen. Interview data included similar constructive feedback but highlighted the educational and social benefits of the program, which participants noted would have been inaccessible if not offered via telemedicine. CONCLUSION: Study findings confirm the feasibility of delivering the RxEd program to remote communities by using telemedicine. Future research with a focus on the sustainability of this and other models of technology-supported patient education for adults with IA across Ontario is warranted.
31431948 The 8-foot up and go test is the best way to assess physical function in the rheumatoid ar 2018 OBJECTIVES: RA is characterized by poor physical function, which compromises patients' quality of life and outcome. Clinical assessment of function is usually performed using self-reported questionnaires, such as the Multi-Dimensional HAQ (MDHAQ) and the Short Form-36 (physical component) (SF36-PC). However, such subjective measures may not accurately reflect real functional status. This study aimed to determine: (i) which clinically practicable objective test best represents overall physical function; and (ii) the extent to which self-reported subjective functional measures reflect objectively assessed function. METHODS: Objective [isometric knee extensor strength, handgrip strength, sit-to-stands in 30 s, 8-foot up and go (8'UG), 50-foot walk (50'W) and estimated aerobic capacity (V̇O(2)max)] and subjective (MDHAQ and SF36-PC) measures of function were correlated with one another to determine the best overall test of functional status in 82 well-controlled RA patients (DAS28 (s.d.) = 2.8 (1.0)). RESULTS: In rank order of size, averaged correlations (r) to the other outcome measures were as follows: 8'UG: 0.650; 50'W: 0.636; isometric knee extensor strength: 0.502; handgrip strength: 0.449; sit-to-stands in 30 s: 0.432; and estimated V̇O(2)max: 0.358. The MDHAQ was weakly (0.361) and the SF36-PC moderately correlated (0.415) with objective measures. CONCLUSION: Our results show that the most appropriate measure of objective physical function in RA patients is the 8'UG, followed by the 50'W. We found discordance between objectively and subjectively measured function. In clinical practice, an objective measure that is simple and quick to perform, such as the 8'UG, is advocated for assessing real functional status.
29144542 Autoimmune diseases and breast cancer risk by tumor hormone-receptor status among elderly 2018 Mar 15 The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ-specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)- and progesterone receptor (PR)- status. Here, we evaluate associations between selected systemic and organ-specific autoimmune diseases and breast cancer risk overall and by tumor ER- and PR-status. We used linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992-2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer-free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79-0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70-0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83-0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06-1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER-positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER-status were statistically significant (p-heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment.
28465766 Biologic Disease-Modifying Antirheumatic Drugs in a National, Privately Insured Population 2017 Feb BACKGROUND: Spending on biologic drugs is a significant driver of drug expenditures for payers in private health plans. Biologic disease-modifying antirheumatic drugs (DMARDs) are some of the most effective and costly treatments in a physician's arsenal. Understanding the total annual expenditure, the average cost per prescription, and the impact of cost-sharing is important for drug benefit managers. OBJECTIVE: To assess drug utilization, expenditures, out-of-pocket (OOP) cost, and price trends of biologic DMARDs in patients with rheumatoid arthritis (RA) in a large managed care organization. METHODS: We conducted a retrospective database analysis of pharmacy claims data from January 2004 to December 2013 using the Optum Clinformatics Data Mart database, which covers 13.3 million lives. Pharmacy claims for 40,373 patients with RA were identified during the study period. In all, 9 biologic DMARDs approved for the treatment of RA, including infliximab, etanercept, adalimumab, certoizumab, golimumab, tocilizumab, anakinra, abatacept, and rituximab, and 1 nonbiologic oral, small molecule-targeted synthetic drug, tofacitinib, were included in this study. Descriptive statistics were used to analyze the total annual number of prescriptions, the total annual expenditures, the average annual cost per drug (a proxy of drug price), and the average OOP cost (copay plus deductible and coinsurance). All measurements were also stratified by study drugs and by insurance type. RESULTS: Of the 40,373 patients with RA included in the study, approximately 76% were female (mean age, 55 years at diagnosis). Approximately 77% of the patients were white, and almost 48% lived in the South or Midwest region of the United States. Approximately 62% of patients had a point of service insurance plan. Expenditures on biologic DMARDs increased from $166 million in 2004 to $243 million in 2013, and the number of prescriptions and refills increased from 59,960 in 2004 to 105,295 in 2013. Prescriptions for biologic DMARDs increased more than 20% per patient from 2004 to 2013. The average cost per prescription remained relatively unchanged, at approximately $2300 per prescription, but the OOP expenditures increased from $36 (2.5%) per prescription to $128 (7%) during the study period. The OOP expenditures increased the most in HMO plans and in plans categorized as other (284% and 388%, respectively). CONCLUSIONS: Spending on biologic DMARDs has been primarily driven by an increase in prescribing rates, as the average amount reimbursed per prescription remained relatively unchanged over time, despite a regular annual increase to the average wholesale acquisition cost of 2% to 10%. The OOP burden for patients has increased, but this does not appear to have limited the use of biologic DMARDs. The entrance of new biologic and nonbiologic DMARDs into the market in the past few years is eroding the market share for several established drugs, and may lead to different results, warranting a study of new trends.
28196776 EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of th 2018 Jan OBJECTIVES: Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. METHODS: We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. RESULTS: In the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3±9.6 years from rheumatic disease onset and 58.7±47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2±24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed (P>0.05 in all comparison). CONCLUSIONS: The current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions.