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ID PMID Title PublicationDate abstract
28898908 Influence of High-Dose Folic Acid on Methotrexate Efficacies and Safety in Japanese Rheuma 2017 Dec Backgrounds Folic acid dose at ≦5 mg/week has been recommended for rheumatoid arthritis (RA) patients to decrease risk of methotrexate adverse effects. However, higher doses of folic acid is used in some cases. We examined the influence of high-dose folic acid on methotrexate efficacies and safety in Japanese RA patients. Methods 502 RA patients of four hospitals prescribed methotrexate and folic acid were included. These patients were divided into two subgroups according to the threshold of folic acid dose by 5 mg/week. Basic patient characteristics, methotrexate doses, and the efficacies or adverse effects of methotrexate were retrospectively compared between the two patient subgroups. Results The frequency of folic acid use at doses higher than 5 mg/week was significantly different between the four hospitals (P<0.001). The prevalence of methotrexate adverse effects was not significantly different between the patients taking folic acid less and more than 5 mg/week. However, in the lower dose methotrexate subgroup (≦8 mg/week), the prevalence of patients exhibiting abnormal serum ALT concentrations in the patients using higher (>5 mg/week) dose of folic acid was significantly higher than that in the lower (≦5 mg/week) folic acid-treated subgroup (P=0.029). Folic acid dose between patients taking methotrexate less and more than 8 mg/week was not significantly different. Major conclusion Folic acid dose was dependent on the hospitals, while efficacies and hepatotoxicity of methotrexate was not basically different between patients taking less and more than 5 mg/week of folic acid.
28477078 Memory B Cells and Response to Abatacept in Rheumatoid Arthritis. 2017 Oct Abatacept is a fusion protein (CTLA4-Ig) and therapeutic molecule labeled for the treatment of rheumatoid arthritis (RA). Abatacept acts both by disrupting the CD28-mediated activation of T cells and by interacting with CD80/CD86 molecules present on antigen presenting cells such as monocytes and memory B cells. Accordingly and to evaluate clinical and biological parameters associated with response to abatacept, a retrospective monocentric study was conducted in 43 patients with RA, and the clinical response was evaluated at 6 months according to EULAR response criteria. Median age of the patients was 59.8 ± 15.1 years including 35 females and 8 males. At baseline, no difference was observed between non-responders (NR, n = 11), moderate responders (MR, n = 21), and good responders (GR, n = 11) to abatacept with regards to demographic, biological, and clinical characteristics of the patients (age, sex, anti-CCP, RF, FcγR3A V158F polymorphism, and C3/C4 complement reduction). Moreover, peripheral blood lymphocyte phenotyping was performed by flow cytometry revealing in 30 RA patients compared to controls (n = 45; median age 56.7 ± 13.5 years) that the initial CD19(+) B cell count was reduced in NR and MR but not in GR. No differences were observed with regards to total lymphocyte, T cell, and NK cell counts. Next, we further explored the effects of abatacept on B cell subsets (IgD/CD38 in panel 1 and IgD/CD27 in panel 2) and observed that the basal level of CD38(+) and/or CD27(+) memory B cell count was important for an abatacept response and that a selective effect of abatacept was observed on memory B cells after 6 months. In conclusion, and although these data need to be confirmed in an independent cohort, our data support a role for memory B cells in the mechanism of action of abatacept in RA.
28927747 Astrocyte elevated gene-1 promotes inflammation and invasion of fibroblast-like synoviocyt 2017 Dec Astrocyte elevated gene-1 (AEG-1) was initially induced by HIV-1 infection and involved in tumor progression, migration and invasion as a nuclear factor-κB (NF-κB)-dependent gene. The present study we intended to investigate the protein expression of AEG-1 significantly associated with rheumatoid arthritis. Western blot analysis and immunohistochemistry demonstrated that AEG-1 was upregulated in synovial tissue of RA patients compared with the controls. Double immunofluorescent staining suggested that AEG-1 was expressed in fibroblast-like synoviocytes (FLS) of RA patients. Furthermore, the expression of AEG-1 in FLS was increased in time-dependent manner by TNF-α stimulation. Upon TNF-α-treated FLS, AEG-1 transferred from the cytoplasm to nucleus where it interacted with the p65 subunit of NF-κB, as examined by immunoprecipitation and immunofluorescent staining assay. Moreover, the inhibition of AEG-1 by RNA interference significantly suppressed TNF-α-induced IL-6 and MMP-3 expression, leading to attenuation of FLS migration and invasion and markedly decreased the phosphorylation of P65 and IκBα, as well as AKT in FLS. Collectively, Our findings provided evidence that AEG-1 contributed to the production of inflammatory cytokines, migration and invasion of RA FLS, and underscored the importance of AEG-1 in the inflammation process of RA.
27788309 Brief Report: The Role of Rare Protein-Coding Variants in Anti-Tumor Necrosis Factor Treat 2017 Apr OBJECTIVE: In many rheumatoid arthritis (RA) patients, disease is controlled with anti-tumor necrosis factor (anti-TNF) biologic therapies. However, in a significant number of patients, the disease fails to respond to anti-TNF therapy. We undertook the present study to examine the hypothesis that rare and low-frequency genetic variants might influence response to anti-TNF treatment. METHODS: We sequenced the coding region of 750 genes in 1,094 RA patients of European ancestry who were treated with anti-TNF. After quality control, 690 genes were included in the analysis. We applied single-variant association and gene-based association tests to identify variants associated with anti-TNF treatment response. In addition, given the key mechanistic role of TNF, we performed gene set analyses of 27 TNF pathway genes. RESULTS: We identified 14,420 functional variants, of which 6,934 were predicted as nonsynonymous 2,136 of which were further predicted to be "damaging." Despite the fact that the study was well powered, no single variant or gene showed study-wide significant association with change in the outcome measures disease activity or European League Against Rheumatism response. Intriguingly, we observed 3 genes, of 27 with nominal signals of association (P < 0.05), that were involved in the TNF signaling pathway. However, when we performed a rigorous gene set enrichment analysis based on association P value ranking, we observed no evidence of enrichment of association at genes involved in the TNF pathway (P(enrichment)  = 0.15, based on phenotype permutations). CONCLUSION: Our findings suggest that rare and low-frequency protein-coding variants in TNF signaling pathway genes or other genes do not contribute substantially to anti-TNF treatment response in patients with RA.
28943207 Supramolecular nano-engineered lipidic carriers based on diflunisal-phospholipid complex f 2017 Nov 25 Diflunisal (DIF) is used for treatment of rheumatoid arthritis, osteoarthritis etc. DIF-phospholipid complex (DIF-PL complex) was prepared by solvent-evaporation method and characterized by molecular docking studies, SEM, FTIR, DSC, PXRD studies. Further, the DIF-PL complex was incorporated into supramolecular nano-engineered lipidic carriers (SNLCs) for transdermal delivery. The optimization exercise was done using Face centered cubic design (FCCD) after screening of variables by L8 Taguchi orthogonal array design. The optimized SNLC formulation depicted average particle size (188.1nm), degree of entrapment (86.77±3.33%), permeation flux (5.47±0.48μg/cm(2)/h) and skin retention (17.72±0.68μg/cm(2)). The dermatokinetic studies revealed the higher concentration of DIF in dermis. The Confocal laser scanning microscopy (CSLM) studies revealed penetration of SNLCs into the deeper layers of skin. The results of mice ear edema depicted significant inhibition of ear edema (76.37±12.52%; p<0.05). In CFA induced rheumatoid arthritis model, the inhibition of paw edema was significantly higher (73.85±14.5%). The levels of TNF-α were reduced in synovial fluid (146.74±1.69pg/mL) and serum (132.43±2.70pg/mL). Furthermore, the licking and biting time was reduced in formalin induced hyperalgesia model. Hence, it can be concluded that dual formulation strategy based SNLCs were promising in treatment of pain and inflammation associated with rheumatoid arthritis.
29273832 Early hearing loss detection in rheumatoid arthritis and primary Sjögren syndrome using e 2018 Feb The aim of this study is to evaluate the hearing behavior of rheumatoid arthritis (RA) and primary Sjögren syndrome (PSS) patients and compare them with a healthy control group and with each other. A comparative cross-sectional study was performed with a group of 117 female RA patients, a group of 60 female PSS patients, and a 251 female healthy control group. Every subject underwent a series of studies including high-frequency audiometry, speech audiometry, and tympanometry. The high-frequency audiometry measured 250 to 16,000 Hz. The 117 patients with RA and the 60 with PSS were diagnosed according to American College of Rheumatology criteria / ACR 2010, and the validated classification of the American-European Consensus Group. Hearing loss was present in 36.8% of the RA group in 500-3000 Hz, 68.4% in 4000-8000 Hz, and 94.9% in 10,000-16,000 Hz. Hearing loss was present in 60% of the PSS group in 500-3000 Hz, 70% in 4000-8000 Hz, and 100% in 10,000-16,000 Hz. The hearing impairment prevalence of both groups was significantly different (p < 0.05) when compared with the healthy control group. We also compared the hearing thresholds between RA and PSS patients, finding a significant hearing threshold increase in 500-3000 Hz of the PSS group. This study consolidates the association between RA and PSS with hearing impairment. A deeper hearing loss was reported in PSS than in RA patients, demonstrating a greater auditory and speech recognition repercussion.
28990250 Galectin-3 is Persistently Increased in Early Rheumatoid Arthritis (RA) and Associates wit 2017 Dec Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 μg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 μg/l [2.6;4.9], P = 0.05) and controls (3.8 μg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti-CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes.
28412709 The Association of Low Income with Functional Status and Disease Burden in German Patients 2017 Jun OBJECTIVE: To assess the influence of income on self-reported disease and work productivity outcomes. METHODS: Persons with rheumatoid arthritis (RA) diagnosis (International Classification of Diseases, 10th ed. codes M05/M06) on health insurance claims data in at least 2 quarters of 2013 were randomly selected. They were mailed questionnaires covering RA diagnosis, household income, functional capacity [Hannover functional status questionnaire (FFbH), 0-100], RA Impact of Disease questionnaire (RAID; 0-10), self-reported swollen joint count (SJC; 0-48), tender joint count (TJC; 0-50), and effect of RA on work productivity (change of work, fewer working hours, sick leave, application for disability pension, and others). Weighted multivariable linear regression models were used to assess the association between income and disease outcomes. RESULTS: A total of 1492 persons of working age who confirmed RA diagnosis were available for analysis. The mean age was 55 years, 82% were women, and 74% were under rheumatologic care. A total of 27%, 52%, and 21% had a low (< €1500), medium (€1500-3200), and high monthly income (> €3200), respectively. Respondents with low income had the worst mean FFbH, RAID, SJC, and TJC values. This was confirmed in the regression model: mean FFbH low versus high income -8.65 (95% CI -9.72 to -7.58), RAID 0.73 (0.59-0.86), and SJC 3.47 (2.86-4.08). Sick leave (8.7%/3.5%/1.8%) and disability pension (18.1%/9.6%/6.9%) were more frequent in patients with low versus medium versus high income (p < 0.05). CONCLUSION: The association of low income with a higher disease burden, more functional disability, and higher rates of work loss emphasizes the need to focus on these outcomes when choosing treatment strategies for patients in the lower income groups.
29172405 Risk of malignancy in patients with rheumatoid arthritis after anti-tumor necrosis factor 2019 May BACKGROUND/AIMS: Inhibition of tumor necrosis factor (TNF) is an effective treatment for rheumatoid arthritis (RA), but safety concerns about malignancy remain. The aim of this study was to evaluate cancer risk in RA patients treated with TNF inhibitors (TNFi), based on Korean Nationwide Health Insurance claims data. METHODS: Patients with seropositive RA were selected from the health insurance database containing all citizens' medical information, based on both RA diagnosis codes and medications. Between 2010 and 2014, RA patients treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and TNFi were enrolled and followed up. We compared the cancer incidence between patients treated with TNFi and csDMARDs using incidence rate ratios (IRRs) after adjustment for age, gender, and observational periods. RESULTS: Of 45,423 selected patients with seropositive RA, 2,337 were treated with TNFi and 43,086 were treated with csDMARDs. The TNFi group was younger and was followed-up for a longer duration. During the observational period, 1,732 and 49 cases of cancer were detected in patients treated with csDMARDs and TNFi, respectively. Old age and male sex were associated with cancer occurrence. Adjusted IRRs for all cancers and common cancers demonstrated that cancer incidence did not differ significantly between the TNFi group and csDMARDs group (IRR = 0.913 for all cancers, p = 0.546). CONCLUSION: This study revealed that cancer incidence was similar in RA patients treated with TNFi and csDMARDs. Anti-TNF therapy may be a safe therapeutic option for RA treatment, in terms of malignancy.
29221579 Biomarkers in connective tissue diseases. 2017 Dec Autoimmune connective tissue diseases are clinically variable, making biomarkers desirable for assessing future disease risk, supporting early and accurate diagnosis, monitoring disease activity and progression, selecting therapeutics, and assessing treatment response. Because of their correlations with specific clinical characteristics and often with disease progression, autoantibodies and other soluble mediators are considered potential biomarkers. Additional biomarkers might reflect downstream pathologic processes or appear because of ongoing inflammation and damage. Because of overlap between diseases, some biomarkers have limited specificity for a single autoimmune connective tissue disease. This review describes select current biomarkers that aid in the diagnosis and treatment of several major systemic autoimmune connective tissue disorders: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody-associated vasculitides. Newly proposed biomarkers that target various stages in disease onset or progression are also discussed. Newer approaches to overcome the diversity observed in patients with these diseases and to facilitate personalized disease monitoring and treatment are also addressed.
28600350 Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibito 2017 Oct OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. METHODS: This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR. RESULTS: In 10 patients who received ICI therapy (all anti-PD-1 or anti-PDL1 antibodies), RA or PMR developed at a median of 1 month (1 to 9) after exposure. No patient had pre-existing rheumatic or autoimmune disease. RA developed in six patients; all six were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and four for rheumatoid factor. Anti-CCP antibodies were detected in two out of three patients tested before immunotherapy. Disease-modifying antirheumatic drugs were needed for three patients; the three others received corticosteroids or non-steroid anti-inflammatory drugs. PMR was diagnosed in four patients, all responded to corticosteroids. Despite these IrAEs, immunotherapy was pursued for all but one patient until cancer progression. CONCLUSIONS: This is the first description of RA occurring after ICI therapy for cancer. PMR can also occur after ICI, particularly after anti-PD-1 therapy. All cases responded to corticosteroids or with immunosuppressive therapy. Collaboration between rheumatologists and oncologists is crucial and could lead to better recognition and care of these patients.
27174398 Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical 2017 Mar OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. METHODS: We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). RESULTS: The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. CONCLUSIONS: Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates.
29474183 Health-Related Quality of Life and Functional Ability of Patients with Rheumatoid Arthriti 2018 May OBJECTIVES: To assess the health-related quality of life and functional ability of patients with rheumatoid arthritis (RA) using the Thai EuroQol five-dimensional questionnaire (EQ-5D) and the Thai Health Assessment Questionnaire (HAQ), and to analyze correlations between the scores from both questionnaires. METHODS: This cross-sectional study was conducted among 221 patients with RA aged 18 years or older at a tertiary care hospital in Thailand. Data collection methods included individual patient interviews and data gathering from medical records. The correlations between the EQ-5D and HAQ scores were analyzed using Spearman's rank correlation coefficients. RESULTS: Most patients were female (78.3%), aged 41 to 60 years (57.0%), having had RA for 12 to 60 months (43.0%), and being in an active disease state (60.6%). From the EQ-5D, most patients reported no problems in each dimension, except for mobility and pain/discomfort. For the HAQ, most patients reported no difficulty for almost all activities, except for arising. The medians (interquartile ranges) for the EQ-5D utility, EuroQol visual analogue scale (EQ VAS), and HAQ scores were 0.65 (0.55-0.73), 70 (50-80), and 0.25 (0.00-0.81), respectively. The Spearman's rank correlation coefficients were 0.42 for the EQ-5D utility and EQ VAS scores (P = 0.01), -0.65 for the EQ-5D utility and HAQ scores (P < 0.001), and -0.39 for the EQ VAS and HAQ scores (P < 0.001). CONCLUSIONS: The health-related quality of life and functional ability of most patients in our study were partially affected by the disease. The EQ-5D and HAQ scores significantly correlated at a moderate to strong level.
29032353 Rates of Joint Replacement Surgery in New Zealand, 1999-2015: A Comparison of Rheumatoid A 2017 Dec OBJECTIVE: To determine rates of joint replacement for people with rheumatoid arthritis (RA) and osteoarthritis (OA) and to examine the characteristics of those receiving elbow replacements. METHODS: Data were extracted from the New Zealand Joint Registry from 1999 to 2015 and annual rates calculated. RESULTS: Rates of joint replacement increased over time for OA but not RA. Elbow replacement was the only procedure performed more commonly in RA. CONCLUSION: There has been a substantial increase in joint replacement for OA in New Zealand. For RA, where access to biologics has been limited to those with erosions, joint replacement rates have not declined, with the exception of elbow replacements.
28508937 The Prevalence of Oropharyngeal Dysphagia in Adults Presenting with Temporomandibular Diso 2017 Oct Temporomandibular disorders (TMDs) are the most frequent non-dental orofacial pain disorders and may be associated with rheumatoid arthritis (RA), resulting in oropharyngeal dysphagia (OD). However, clinicians' understanding of involvement with OD caused by RA-related TMDs is limited and the methodological quality of research in this field has been criticised. Therefore, the aim of this study was to systematically review the prevalence of oral preparatory and oral stage signs and symptoms of OD in adults presenting with TMDs associated with RA. A systematic review of the literature was completed. The following electronic databases were searched from inception to February 2016, with no date/language restriction: EMBASE, PubMed, CINAHL, Web of Science, Elsevier Scopus, Science Direct, AMED, The Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses A & I. Grey literature and reference lists of the included studies were also searched. Studies reporting the frequency of OD in adults presenting with TMD and RA were included. Study eligibility and quality were assessed by three independent reviewers. Methodological quality was assessed using the Down's and Black tool. The search yielded 19 eligible studies. Typical difficulties experienced by RA patients included impaired swallowing (24.63%), impaired masticatory ability (30.69%), masticatory pain (35.58%), and masticatory fatigue (21.26%). No eligible studies reported figures relating to the prevalence of weight loss. Eligible studies were deemed on average to be of moderate quality. Study limitations included the small number of studies which met the inclusion criteria and the limited amount of studies utilising objective assessments. Valid and reliable prospective research is urgently required to address the assessment and treatment of swallowing difficulties in RA as TMJ involvement may produce signs and symptoms of OD.
28410854 The correlation of serum bilirubin levels with disease activity in patients with rheumatoi 2017 Jun BACKGROUND: We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). METHODS: We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. RESULTS: Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, P<0.001). Serum bilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. CONCLUSIONS: Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA.
26792597 Prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease acti 2017 Jan OBJECTIVES: To analyse the prevalence of hypothyroidism in rheumatoid arthritis (RA) patients and to elucidate its correlation with disease activity. METHODS: A total of 52 RA patients were enrolled in this study. All patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing. RESULTS: Hypothyroidism (defined as having a TSH level >4.20 μIU/mL) was observed in 20/52 (38.4%). Erythrocyte sedimentation rates (ESR) were found significantly elevated in patients with hypothyroidism compared to those without (36.3 ± 24.2 vs. 24.6 ± 9.0 mm/h). Disease activity parameters such as DAS-28-ESR, tender joint count; VAS scores were also significantly higher in the former. A significant correlation with serum TSH levels was observed with ESR and DAS-28-ESR. CONCLUSION: Thyroid function test should be included in clinical evaluation of RA patients.
27878345 Low vaccination rates among patients with rheumatoid arthritis in a German outpatient clin 2017 Feb Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections due to two reasons: the disease itself and the immunosuppressive therapy. Vaccinations against preventable diseases are therefore of utmost importance for these group of patients. To estimate vaccination frequencies among patients with rheumatoid arthritis, we studied patients in a survey and calculated vaccination rates based on their vaccination documents. Patients have been recruited from our outpatient clinic during one of their routine visits. For the statistical analysis, they have been divided by age (≥60 vs <60 years) and medication (DMARD, Biologics, TNF inhibitors) for further subgroup analysis. Among the studied patients (n = 331), we found rather low vaccination rates, in particular for the strongly recommended vaccines against Pneumococcus and Influenza (33 and 53%, respectively). Furthermore, protection rates for important basic vaccinations, e.g. against Pertussis, were found to be very low with 12% only. Beside these findings, we saw age-dependent differences for a variety of vaccines: while Pneumococcus and Influenza vaccines were more often given to patients ≥60 years, MMR, Pertussis, Diphtheria and Hepatitis were significantly more often applied to younger patients. Vaccination rates have to be improved among RA patients, in particular for vaccines protecting from respiratory tract infections such as Pneumococcus.
29127626 Impact of Infliximab and Etanercept Biosimilars on Biological Disease-Modifying Antirheuma 2017 Dec OBJECTIVE: Biological disease-modifying antirheumatic drugs (bDMARDs) are effective but expensive options for treating rheumatoid arthritis. The introduction of infliximab and etanercept biosimilars presents a significant potential cost saving in a financially constrained health system such as the National Health Service (NHS) in the UK. This study examines the impact of the introduction of infliximab and etanercept biosimilars on the utilisation of bDMARDs and subsequent budget impact. METHODS: We conducted an interrupted time series analysis of secondary care utilisation data in rheumatology specialities from the DEFINE database, between March 2014 and February 2017. RESULTS: The cumulative cost savings from the introduction of infliximab and etanercept biosimilars was £38.8 million over 2 years. There was a statistically significant increase in average monthly utilisation of bDMARDs for adalimumab (0.48%), certolizumab pegol (1.90%), golimumab (3.06%), abatacept (2.97%) and tocilizumab (2.24%), but not for etanercept. In contrast, the overall utilisation of infliximab decreased slightly by an average of 0.03% per month. The introduction of infliximab biosimilars negatively affected the monthly utilisation of branded infliximab significantly. Similarly, the introduction of an etanercept biosimilar negatively affected the monthly utilisation of branded etanercept significantly. CONCLUSIONS: The introduction of bDMARDs biosimilars has resulted in considerable cost savings to the NHS, with the branded products reducing their prices in response to the availability of less expensive biosimilars and competition between the biosimilars themselves. Our results also suggest that when a biosimilar is available for a directly comparable branded molecule, price is the key influencing factor in the prescribing of a specific product.
28325148 The Potent Inhibitory Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunos 2017 OBJECTIVE: To investigate the inhibitory effect of β-D-mannuronic acid (M2000) on anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), antidouble strand DNA (anti-dsDNA) and acute phase reactants in rheumatoid arthritis (RA) patients. METHODS: The study included 40 patients with RA who had an inadequate response to conventional therapy (identifier: IRCT2014011213739N2). The patients were permitted to continue the conventional therapy excluding NSAIDs. 21 of them were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks and the others did not. Serum samples were collected at baseline, 4 weeks and 12 weeks after treatment and were tested for the serum level of anti-CCP and anti-dsDNA antibodies using enzyme linked immunosorbent assay. The serum level of RF and C-reactive proteins (CRP) was determined by the immunoturbidimetric assay, respectively. RESULTS: At baseline, all patients in the M2000 treated group and the control group were positive for anti-CCP, RF. moreover, 4 of 21 (19%) in the M2000 treated group and 2 of the 19 (10.5%) patients in the control group were positive for anti-dsDNA antibodies, respectively. The serum levels of anti-CCP, RF and anti-dsDNA were decreased significantly after M2000 therapy (p<0.001, p<0.001 and p<0.001, respectively). The reduction in the level of anti-CCP was positively correlated with disease activity, swollen joint count and CRP. Furthermore, the level of inflammatory markers ESR and CRP decreased significantly after M2000 therapy (p<0.001 and p<0.004, respectively). CONCLUSION: M2000 shows inhibitory effect on anti-CCP, RF, anti-dsDNA antibodies and acute phase reactants in RA patients.