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ID PMID Title PublicationDate abstract
28966210 Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis. 2017 Dec OBJECTIVE: Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions. METHODS: Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated. RESULTS: The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1-4.5), compared to those taking 0-5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2-2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR. CONCLUSION: PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.
28407990 Mandibular movements in older people with rheumatoid arthritis. 2017 May OBJECTIVE: The aim of this study was to compare the mandibular movements in older people with and without temporomandibular disorder (TMD) associated with rheumatoid arthritis (RA). STUDY DESIGN: Thirty partially or completely edentulous older adults (65.33 ± 4.7 years) were assigned to 2 groups: (1) with RA and TMD and (2) without RA and TMD. Chewing movements of the jaws during mastication of the test material (Optocal) and the range of mandibular movements were evaluated by using the JT-3-D kinesiographic device before and after new removable prosthesis insertion. Multiple comparisons were made with analysis of variance (ANOVA) and the Tukey-Kramer test. RESULTS: Comparisons between the 2 groups before and after new prosthesis insertion revealed that the RA and TMD group had reduced opening angles (P < .05) during chewing. After insertion of new prostheses, both groups showed increased opening and closing angles during chewing (P < .05). The mandibular range of motion results showed that patients with RA and TMD exhibited lower aperture and laterality movements (P < .05) compared with controls before and after new prosthesis insertion. However, there was an increase in aperture, lefty laterality, and protrusion values after new prosthesis insertion in both groups. CONCLUSIONS: TMD associated with RA may impair mandibular movements. Well-fitted prostheses may improve mandibular movements in older adults, especially those with RA.
28107624 Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis. 2017 Apr 19 An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ)-Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio)propionyl hydrazide (PDPH)-poly(ethylene glycol)-N-hydroxysuccinimide (PDPH-PEG-NHS). The successful synthesis of TCZ-ALD conjugate is corroborated by (1)H NMR, the purpald assay, mass spectrometry (MS), and high performance liquid chromatography (HPLC). In vitro binding affinity and cell viability tests confirmed the biological activity of TCZ-ALD conjugate. Furthermore, in vivo efficacy of TCZ-ALD conjugate is confirmed by microcomputed tomography (CT), histology, and Western blot analyses for the treatment of RA.
27783394 Association of NKG2D gene variants with susceptibility and severity of rheumatoid arthriti 2017 Mar NKG2D (KLRK1) is a C-type lectin receptor present on natural killer (NK) cells, γδ, CD8(+) and CD4(+) T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4(+) T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with rheumatoid arthritis (RA). Eight different single nucleotide polymorphisms (SNP) in the NKG2 gene were genotyped in 236 patients with RA and 187 controls using Taqman 5' nuclease assays. NKG2D genotype/allele frequency did not differ between patients and controls. Subgroup analysis showed that the frequency of A allele of NKG2D9 and T allele of NKG2D10 was significantly higher in patients with deformities (a marker of severe disease) [11 versus 5%, Pc = 0·03, odds ratio (OR) = 2·44, 95% confidence interval (CI) = 1·09-5·98 and 10 versus 4%, Pc = 0·04, OR = 2·45, 95% CI = 1·05-6·39, respectively], while the frequency of alleles G of NKG2D9 and A of NKG2D10 was greater in patients without deformities (Pc = 0·03, OR = 0·41, 95% CI = 0·17-0·91 and Pc = 0·04, OR = 0·41, 95% CI = 0·16-0·96). Similar trends of association were observed with deforming phenotype of RA in female patients and deforming young onset RA subgroups. Haplotype analysis revealed that the frequency of haplotype G-C-A-G-A-T-C-C was higher in patients than in controls (12 versus 8%, P = 0·04, OR = 1·61, 95% CI = 1·01-2·55), suggesting that it may predispose to RA. Our study suggests that the NKG2D gene polymorphisms may modify the risk of development and severity of RA.
28810929 The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis. 2017 Aug 15 BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis. Comparing young and middle-aged K/BxN T cells of the same TCR specificity allows us to study T cells with an age focus eliminating a key variable: TCR repertoire alteration with age. In addition to joints, we also studied pathological changes in the lung, an important extra-articular RA manifestation. We used flow cytometry to evaluate T follicular helper (Tfh) and T helper 17 (Th17) cells, as they both contribute to autoantibody production, a key disease index in both RA and K/BxN arthritis. RESULTS: Middle-aged K/BxN mice had aggravated arthritis and pathological changes in the lung compared to young mice. Middle-aged mice displayed a strong accumulation of Tfh but not Th17 cells, and had defective Th17 differentiation and low expression of interleukin-23, a critical cytokine for Th17 maintenance. Although a soaring Tfh cell population accompanied by robust germinal center B cell responses were found in middle-aged mice, there was decreased cycling of Tfh cells, and SFB only induced the non-Tfh cells to upregulate Bcl-6, the Tfh master transcription factor, in the young but not the middle-aged group. Finally, the accumulated Tfh cells in middle-aged mice had an effector phenotype (CD62L(lo)CD44(hi)). CONCLUSION: Age-dependent Tfh cell accumulation may play a crucial role in the increased autoimmune disease phenotype in middle-age. SFB, a potent stimulus for inducing Tfh differentiation, fails to promote Tfh differentiation in middle-aged K/BxN mice, suggesting that most of the middle-aged Tfh cells with an effector phenotype are Tfh effector memory cells induced at an earlier age. Our results also indicate that exposure to immunomodulatory commensals may allow the young host to develop an overactive immune system reminiscent of that found in the middle-aged host.
28267716 An emerging role for neutrophil extracellular traps in noninfectious disease. 2017 Mar 7 The production of neutrophil extracellular traps (NETs) is a process that enables neutrophils to help catch and kill bacteria. However, increasing evidence suggests that this process might also occur in noninfectious, sterile inflammation. In this Review, we describe the role of NETosis in autoimmunity, coagulation, acute injuries and cancer, and discuss NETs as potential therapeutic targets. Furthermore, we consider whether extracellular DNA is always detrimental in sterile inflammation and whether the source is always NETs.
29237149 Association of Antibodies to Citrullinated Protein Antigens with Blood Pressure in First-D 2017 BACKGROUND: Hypertension is more common in patients with rheumatoid arthritis (RA) than in the general population. It is unknown whether hypertension is due to RA-related medications or the disease itself. Therefore, we sought to investigate associations between RA-related autoantibodies, specifically antibodies to citrullinated protein antigens (ACPA) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in first-degree relatives of RA patients, who were free of RA and RA-related medications. We hypothesized that a greater number of detectable ACPA would be associated with high SBP and DBP, independent of other risk factors in these first-degree relatives. METHODS: We evaluated associations between ACPA and SBP and DBP in a cross-sectional study of 72 first-degree relatives (defined as parent, child, or sibling) of RA patients. Fifteen ACPA were measured using a Bio-Plex bead-based assay; each was dichotomized as positive/negative based on pre-specified cut-points. Analysis of covariance was used to evaluate associations between ACPA positivity and SBP and DBP, adjusting for age, sex, race, body mass index (BMI), pack-years of smoking, high sensitivity C-reactive protein (hsCRP), and current use of anti-hypertensive medications. RESULTS: Average age was 51 and 69% were women. Mean SBP was 119 ± 18 and DBP was 74 ± 9 mm Hg. Thirty-three (46%) first-degree relatives were positive for ≥1 ACPA; and were younger, had lower BMI, more pack-years of smoking, and higher hsCRP concentrations compared to ACPA negative first-degree relatives. For each additional positive ACPA, SBP was 0.98 ± 0.5 mm Hg (p = 0.05) higher, and DBP was 0.66 ± 0.3 mm Hg (p = 0.04) higher. Anti-cit-fibrinogen A (211-230) positive and anti-cit-filaggrin positive first-degree relatives had 11.5 and 13.9 mm Hg higher SBP (p = 0.02) respectively. Anti-cit-clusterin, cit-filaggrin, and cit-vimentin positive first-degree relatives had 7-8 mm Hg higher DBP (p = 0.03, 0.05, 0.05 respectively), compared to being negative for these individual ACPA. Consistent with associations between ACPA, SBP, and DBP, anti-cyclic citrullinated peptides (anti-CCP2) positive first-degree relatives had 16.4± (p = 0.03) higher SBP and 12.1± mm Hg (p = 0.01) higher DBP than anti-CCP2 negative first-degree relatives. CONCLUSION: In first-degree relatives without RA, ACPA positivity is associated with higher SBP and DBP. Subclinical autoimmune processes and ACPA may play a role in the vascular changes potentially leading to hypertension prior to RA onset.
29110050 Frequency of inflammatory-like MR imaging findings in asymptomatic fingers of healthy volu 2018 Feb OBJECTIVE: To describe the frequency of inflammatory-like findings on MR imaging in asymptomatic volunteers and compare them with patients with known rheumatoid arthritis and psoriatic arthritis. MATERIALS AND METHODS: MR images of fingers in 42 asymptomatic volunteers and 33 patients with rheumatoid/psoriatic arthritis were analyzed. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid/Psoriatic Arthritis MRI Scoring System (RAMRIS/PsAMRIS) and tenosynovitis scoring system were used to assess: bone marrow edema (BME), erosions, tendon sheath fluid/tenosynovitis, joint effusion, and soft-tissue edema. Findings and scores were compared between volunteers and patients. Inter-reader agreement was calculated (intraclass correlation coefficients, ICC). RESULTS: In volunteers, tendon sheath fluid was very common in at least one location (42/42 volunteers for reader 1, 34/42 volunteers for reader 2). BME, erosions, joint effusion, and soft-tissue edema were absent (except one BME in the 3rd proximal phalanx for reader 1). Tendon sheath fluid scores in volunteers and tenosynovitis scores in patients were high (reader 1, 7.17 and 5.39; reader 2, 2.31 and 5.45). Overall, inter-reader agreement was substantial (ICC = 0.696-0.844), except for tendon sheath fluid (ICC = 0.258). CONCLUSION: Fluid in the finger flexor tendon sheaths may be a normal finding and without gadolinium administration should not be interpreted as tenosynovitis. Bone marrow edema, erosions, joint effusion, and soft-tissue edema in the fingers most likely reflect pathology if present.
28737992 Temporal Trends in Use of Biologic DMARDs for Rheumatoid Arthritis in the United States: A 2017 Aug BACKGROUND: Ten biologic disease-modifying antirheumatic drugs (bDMARDs) are available as treatment for rheumatoid arthritis (RA), but relatively little is known about population-level time trends in the use of these agents. OBJECTIVE: To describe time trends in the use of bDMARDs in RA patients with private or public insurance in the United States. METHODS: Claims data from private (Optum Clinformatics, 2004-2015) and public (Medicaid Analytic eXtract [MAX], 2000-2010) insurance programs were used. Patients with RA diagnosis codes and continuous health plan enrollment for 1-year baseline and 1-year follow-up periods were identified into 2 separate cohorts: (1) patients not using any bDMARD or (2) patients using a single bDMARD during the baseline period. Initiation of the first bDMARD from group 1 and switch to a second bDMARD from group 2 was identified as the outcome of interest during the 1-year follow-up period. Using mixed-effects regression models, we calculated yearly rates of initiation and switch for bDMARDs, adjusted for case-mix. We also described the proportion of all initiations and switches accounted for by each agent. RESULTS: There were 113,031 RA patients with public insurance and 97,751 RA patients with private insurance who were included in the study. The rates of initiation of bDMARDs (per 100 patients) increased significantly over time in Medicaid data for incident RA patients (from 1.1 to 3.1, P = 0.0006) and prevalent RA patients (from 4.6 to 10.9, P = 0.008). In Optum Clinformatics data, the rates were stable, with 7.7 to 8.3 per 100 incident RA patients (P = 0.10) and 11.0 to 11.5 per 100 prevalent RA patients (P = 0.12). The rates of switching (per 100 patients) increased over time from 6.4 to 16.0 (P = 0.04) in Medicaid data and 9.1 to 17.0 (P = 0.00003) in Optum Clinformatics data. Use of etanercept as the most common first-line agent was stable at approximately 50% of all biologic initiations, but use of infliximab decreased and the use of newer agents increased. CONCLUSIONS: More RA patients used bDMARDs in recent years, and use of newer agents, including certolizumab, golumumab, and tocilizuamab, is rising, which highlights a need for further comparative safety and effectiveness research of these agents to better guide evidence-based decision making. DISCLOSURES: This study was supported by an investigator-initiated research grant from Pfizer. The study was conducted by the authors independent of the sponsor. The sponsor was given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and determined the final wording. Solomon receives salary support through research support to his hospital from Amgen, Pfizer, AstraZeneca, Genentech, Lilly, Bristol-Myers Squibb, and CORRONA. Kim receives research grants from AstraZeneca, Lilly, Pfizer, Bristol-Myers Squibb, and Genentech. Desai receives research grants from Merck. Study concept and design were contributed by Desai and Kim. Liu took the lead in data collection, along with Jin, Desai, and Kim. All authors contributed equally in the interpretation of the results. The manuscript was written and revised primarily by Desai, along with Kim and the other authors.
28877634 Certolizumab, an anti-TNF safe during pregancy? The CRIB Study results: an interview with 2017 Sep Professor Xavier Mariette, MD, PhD, has served as the Head of the Rheumatology Department of Bicêtre Hospital, Paris-Sud University since 1999, a role he took following 10 years of practice of clinical immunology. Professor Mariette has initiated a number of clinical research studies on biotherapies in autoimmune diseases. He is the head of the French RATIO (Research Axed on Tolerance of Biotherapy) observatory, collecting specific rare serious adverse events in patients treated with anti-TNF. He initiated the French AIR (Autoimmunity and Rituximab) and ORA (Orencia and Rheumatoid arthritis) registries of patients with autoimmune diseases treated with rituximab and abatacept. He initiated clinical trials in Sjögren's syndrome with infliximab, hydroxychloroquine and belimumab. Professor Mariette is involved in basic research, leading a group working on pathogeny of Sjögren's syndrome, relationships between innate immunity and B-cell activation in autoimmunity and the relationships between autoimmunity and lymphoma. Professor Mariette is also very interested in new ways of teaching. In 2007, he participated with other European Experts in the creation of the EULAR Web Course of Rheumatology in 2007. Professor Mariette has been the President of the Scientific Committee of the EULAR meeting, which took place in Berlin in 2012 and is in 2016 the elect Chair of the EULAR standing committee on investigative rheumatology. Professor Mariette is co-author of more than 430 publications referenced in PubMed with an H-index of 61.
28716293 Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion 2017 Aug PURPOSE: Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. METHODS: A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. FINDINGS: Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. IMPLICATIONS: Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications.
28828944 IL-6 is an independent predictive factor of drug survival after dose escalation of inflixi 2018 May OBJECTIVE: We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3 mg/kg IFX. METHODS: Among 42 patients allotted to receive 3 mg/kg IFX, 13 patients showed adequate response (DAS28 < 3.2) and 29 patients required dose escalation to 4.5 or 6 mg/kg after inadequate response (DAS28 ≥ 3.2) to 3 mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival. RESULTS: One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0 pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16 pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712-1.006). In patients with IL-6 levels of less than 5.16 pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16 pg/mL and in those with levels greater than or equal to 5.16 pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p = .011). CONCLUSIONS: The results of our study indicated that a baseline serum level of IL-6 below 5.16 pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.
28013198 Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled a 2017 Apr 1 OBJECTIVES: To investigate changes in neutrophil count and occurrences of infection in RA patients treated with the IL-6 receptor-α inhibitor tocilizumab (TCZ). METHODS: Data were pooled from patients who received i.v. TCZ (4 mg/kg + MTX, 8 mg/kg ± DMARDs, 10 mg/kg) or placebo + DMARDs in phase 3/4 clinical trials, long-term extensions or a pharmacology study. Neutrophil counts were measured routinely according to the Common Toxicity Criteria for Adverse Events grades; TCZ dosing was adjusted if necessary. Covariates associated with decreased neutrophil counts were assessed with multivariate regression analysis. Infection rates within 30 days of neutrophil count changes were calculated per 100 patient-years of TCZ exposure. RESULTS: In placebo-controlled parts of trials, more TCZ-treated than placebo-treated patients had grade 1/2 or 3/4 neutrophil counts (TCZ: 28.2%/3.1%; placebo: 8.9%/0.2%). In placebo-controlled trials + long-term extensions, 4171 patients provided 16204.8 patient-years of TCZ exposure. Neutrophil counts decreased through week 6 from baseline [mean ( s . d .) change, -2.17 (2.16) × 10 9 /l) and remained stable thereafter. Rates (95% CI) of serious infections within 30 days of normal [4.66 (4.31, 5.03)], grade 1/2 [2.48 (1.79, 3.34)] and 3/4 [2.77 (0.34, 10.01)] neutrophil counts were similar. Baseline neutrophil count <2 × 10 9 /l and female gender were associated with grade 3/4 neutrophil counts [odds ratio (OR) (95% CI): 19.02 (6.76, 53.52), 2.55 (1.40, 4.66)]. Patients who stopped TCZ in response to decreased neutrophil count returned more quickly to normal levels than patients who reduced or continued their dose. CONCLUSION: Decreases in neutrophil counts in patients taking TCZ do not appear to be associated with serious infections and are normalized by current risk mitigation guidelines.
27460224 Implementation of protocolized tight control and biological dose optimization in daily cli 2017 Mar OBJECTIVES: To assess the effects of education, guideline development, and individualized treatment advice on rheumatologist adherence to tight control-based treatment and biological dose optimization in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthropathy (SpA) patients. METHOD: This pilot study, among two rheumatologists and two specialized nurses in a general hospital, combined education, feedback, local guideline development, and individualized treatment advice. Outcomes (baseline and 1 year post-intervention) were the percentage of patients with a Disease Activity Score in 28 joints (DAS28) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured during the visit, mean DAS28/BASDAI, and the percentage of patients using a reduced biological dose. DAS28 outcomes only applied to RA and PsA patients, BASDAI outcomes only applied to SpA patients whereas outcomes on biological dose applied to all patients. RESULTS: A total of 232 patients (67% RA, 15% PsA, 18% SpA; 58% female, mean age 56 ± 15 years) were included in the study. The percentage of DAS28 and BASDAI measurements performed increased after the intervention [DAS28 15-51%, odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.5; BASDAI 23-50%, OR 2.2, 95% CI 1.0-5.5], with mean DAS28 and BASDAI scores remaining similar (DAS28: mean difference 0.1, 95% CI -0.3 to 0.5; BASDAI: mean difference 0.03, 95% CI -1.8 to 1.9). Use of a reduced biological dose increased from 10% to 61% (OR 3.9, 95% CI 2.4-6.5). CONCLUSIONS: A multicomponent intervention strategy aimed at rheumatologists can lead to improved adherence to tight control-based treatment and a reduction in the use of biologicals in RA, SpA, and PsA patients.
28321852 Active matrix metalloproteinase-8 and periodontal bacteria depending on periodontal status 2017 Aug BACKGROUND AND OBJECTIVES: The aim of this clinical cross-sectional study was to determine the level of active matrix metalloproteinase-8 (aMMP-8) and periodontal pathogenic bacteria in gingival crevicular fluid in patients with rheumatoid arthritis (RA) with varying periodontal conditions. MATERIAL AND METHODS: In total, 103 patients with RA and 104 healthy controls (HC) were included. The assessment of periodontal status included periodontal probing depth, bleeding on probing and clinical attachment loss. Periodontal disease was classified as healthy/mild, moderate or severe. For the determination of aMMP-8 levels using enzyme-linked immunosorbent assay and periodontal pathogenic bacteria using polymerase chain reaction, samples of gingival crevicular fluid were taken from the deepest gingival pockets. The statistical analyses used included a Mann-Whitney U-test, a chi-squared test or a Fisher's exact test, and the significance level was set at α = 5%. RESULTS: We found that 65% of patients with RA and 79% of HC had moderate to severe periodontal disease (p = 0.02). The prevalence of periodontal pathogens was almost equal (p > 0.05). Furthermore, depending on periodontal disease severity only minor differences in bacterial prevalence were detected. With increasing severity of periodontal disease, higher aMMP-8 levels were observed. Accordingly, a significant difference in patients with moderate periodontal disease (RA: 15.3 ± 13.8; HC: 9.1 ± 9.1; p ≤ 0.01) and severe periodontal disease (RA: 21.7 ± 13.3; HC: 13.1 ± 8.6; p = 0.07) was detected, with a greater tendency in the latter group. CONCLUSION: The increased aMMP-8 levels in the RA group indicate that the presence of RA appears to have an influence on the host response at a comparable level of bacterial load and periodontal disease severity.
28691456 Genetic correlation between rheumatoid arthritis and periodontal disease: the role of sex 2017 Apr The chronic stimulation of the immune system due to the presence of bacterial antigens within periodontal tissues has been associated with several autoimmune diseases, like diabetes mellitus, infective endocarditis or cardiovascular atherosclerosis. The current study aims at evaluating the correlation between Rheumatoid Arthritis (RA) and Periodontal Disease (PD) with special attention to genetic polymorphisms in cytokine expression. A total number of 34 patients affected by RA were recruited. Each of them underwent haematochemical analysis and data were collected for Rheumatoid Factor (RF), Anti-Citrullinated ProteinÂ’s Antibody (CCP) and HLA-BDR1. DAS-28 questionnaire for disease activity was fulfilled by the rheumatologist, while a periodontal examination was carried out by the dental clinician and crevicular fluid samples were collected to evaluate the IL-6, IL-10 and VDR polymorphysms. A connection between CCP and IL-10 polymorphisms was found, with IL-10 expressing protecting tendency against periodontal disease when CCP are found in the bloodstream (p=0.0017). Finally, males mainly expressed IL-10 predisposing genes (p=0.046), while females showed a greater tendency to express RF (p=0.014) and CCP (p=0.050). This paper corroborates the idea of a correlation between sex, IL-10 polymorphisms and RA, which should be studied in depth, since recent papers have shown that IL-10 injected into joints seems to decrease inflammation.
28225768 Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid art 2017 BACKGROUND: Pentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) levels in IRDs, and if s-PTX3 levels were related to other markers of inflammation and to endothelial function (EF). METHODS: We examined s-PTX3, EF and established inflammatory biomarkers in 114 IRD patients from the PSARA study before and after 6 weeks and 6 months of treatment with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNF) therapy with or without MTX co-medication. RESULTS: s-PTX3 levels in all IRD diagnoses were above the upper limit of the reference range. In contrast to established inflammatory markers, in particular CRP and ESR, s-PTX3 levels did not change significantly after 6 weeks and 6 months of anti-rheumatic therapy. There was no difference in change in s-PTX3 levels from baseline to 6 weeks and 6 months between MTX monotherapy and anti-TNF regimens. CRP, ESR and EF were not related to changes in s-PTX3 neither in crude nor adjusted analyses. CONCLUSION: IRD patients have increased s-PTX3 levels, which, in contrast to other inflammatory markers, do not seem to improve within 6 months of therapy with MTX and/or anti-TNF. Thus, s-PTX3 might reflect a persisting immune process, even a causal factor of inflammation, not inhibited by the standard anti-rheumatic treatment. Furthermore, even though s-PTX3 is thought to be a strong predictor of cardiovascular prognosis, it was not related to EF.
27907250 The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Aut 2017 Apr OBJECTIVE: The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA). METHODS: Candidate molecules were identified by gene expression profiling of RA synovitis and validated by quantitative polymerase chain reaction and immunohistochemistry. B cell-specific expression was confirmed by immunofluorescence, immunoblotting, and flow cytometry. The role of Bob1 in pathologic B cell responses was assessed in collagen-induced arthritis (CIA). RESULTS: Transcriptional profiling of RA synovitis revealed a prominent B cell signature, with the transcriptional coactivator Bob1 and its putative target BCMA being among the most up-regulated genes. Further analysis confirmed the microarray data and demonstrated elevated levels of Bob1 in B cells in RA synovium. A functional study showed that Bob1-deficient mice failed to produce pathogenic anti-type II collagen (anti-CII) antibodies and were resistant to CIA. Adoptive transfer of cells from Bob1-deficient and Bob1-sufficient mice to recombination-activating gene 1-null mice demonstrated that Bob1 deficiency exclusively in B cells abrogated germinal center (GC) B cell formation, anti-CII antibody production, and CIA development. Consistent with data from animal studies, immunophenotyping of human B cell subsets revealed increased expression of Bob1, predominantly in centrocytes and centroblasts. Correspondingly, Bob1 expression in RA synovitis was strongly correlated with CD21L, a molecular marker of GCs. In addition, similar Bob1 overexpression and correlation with CD21L expression was evidenced in parotid salivary gland tissue from patients with primary Sjögren's syndrome. CONCLUSION: These expression and functional data identify the transcriptional coactivator Bob1 as a candidate molecular switch of pathogenic B cell responses in autoimmune diseases in humans.
29151519 Tofacitinib Therapy for Rheumatoid Arthritis: A Direct Comparison Study between Biologic-n 2018 Mar 1 Objective This study was designed to directly compare the outcomes of tofacitinib therapy for methotrexate-refractory rheumatoid arthritis (RA) between biologic-naïve patients and patients who had experienced an inadequate response to biological agents. Methods We prospectively enrolled and followed 113 patients who had a high or moderate clinical disease activity index (CDAI) (36 biologic-naïve patients and 77 biologic-experienced patients). Patients received 5 mg of tofacitinib twice daily. Effectiveness and adverse events were examined at month 6 of treatment. Results At month 6, 65 patients (57.5%) reached CDAI50, which is defined as achieving ≥50% improvement. The number of previous biological agents was twice as high in CDAI50 non-responders as in responders (2.2 versus 1.1, p<0.001), but there was no significant difference in the type of previous agents or the reason for discontinuation. According to a multivariate logistic regression analysis, the previous use of biological agents [odds ratio (OR) 4.48, p=0.002] and the concurrent use of prednisolone (OR 2.40, p=0.047) were associated with a failure to achieve a CDAI 50 response. Biologic-naïve patients were more likely to achieve CDAI50 than biologic-experienced patients (80.6% versus 46.8%, p=0.001). Mean CDAI values were higher in biologic-experienced patients (11.4 versus 4.8, p=0.001), and remission rates were higher in biologic-naïve patients (41.7% versus 11.7%, p=0.001). Biologic-naïve patients more rapidly achieved remission. Rates of discontinuation resulting from adverse events were similar in both groups. Conclusion Although tofacitinib can provide an effective treatment option for intractable RA patients, its impact on outcomes is lower in patients with previous biologic failure.
29229311 An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis a 2018 Jan BACKGROUND: Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion. METHOD: Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months. Furthermore, 48 healthy individuals, median age = 60 years were immunized with two doses, six months apart. Anti-hepatitis A antibodies were measured at 0, 1, 2, 6, 7 and 12 months. RESULTS: Two months after the initial vaccination, 88% of the RA patients had protective antibodies, compared to 85% of the healthy individuals. There was no significant difference between the two vaccine schedules. At twelve months, 99% of RA patients and 100% of healthy individuals had seroprotective antibodies. CONCLUSION: An extra priming dos of hepatitis A vaccine prior to traveling offered an acceptable protection in individuals treated with TNFi and/or MTX. This constitutes an attractive pre-travel solution to this vulnerable group of patients.