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ID PMID Title PublicationDate abstract
29246532 An e-health interactive self-assessment website (Sanoia(®)) in rheumatoid arthritis. A 12 2018 Dec INTRODUCTION: Sanoia is an online interactive electronic e-health platform developed to allow patient self-assessment and self-monitoring. The objective was to assess in rheumatoid arthritis (RA) patients, the efficacy on patient-physician interactions, of giving access to Sanoia. METHODS: In this French, multi-center, 12-months randomized controlled trial (CarNET: NCT02200068), patients with RA and internet access were randomized to: access without incentives to the Sanoia platform after minimal training, or usual care. The primary outcome was the change from baseline in patient-physician interactions, by the patient-reported Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) questionnaire. The number of accesses to Sanoia was recorded and satisfaction with the platform was assessed through a 0-10 numeric rating scale. Analyses were in intention to treat (ITT), on SAS. RESULTS: Of 320 RA patients (159 Sanoia versus 161 usual care), mean (standard deviation) age was 57.0 (12.7) years, mean (SD) disease duration was 14.6 (11.1) years, 216 (67.5%) were taking a biologic and 253 (79.1%) were female. Mean (SD) PEPPI scores at baseline and 12 months were 38.6 (8.2) and 39.2 (8.0) (delta=+0.60 [5.52]) versus 39.7 (7.3) and 38.8 (8.0) (delta=-0.91 [6.08]) in the Sanoia and control group, respectively (P=0.01). Although mean satisfaction with the platform was very high (1.46 [1.52]), 41 patients (25.7%) never accessed Sanoia. CONCLUSION: Giving RA patients access to the interactive Sanoia e-health platform led to a small improvement in patient-perceived patient-physician interactions. A disjunction between patient satisfaction and access to the platform was noted. E-Health platforms are promising in RA.
30092161 Three-year safety and two-year effectiveness of etanercept in patients with rheumatoid art 2019 Sep Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.
30058434 Adverse events, clinical considerations and management recommendations in rheumatoid arthr 2018 Nov A new class of oral synthetic drugs has been developed for the treatment of rheumatoid arthritis (RA) with the aim of blocking the Janus kinase/signal transducer and activator of transcription (JAK-STAT) system. Tofacitinib and baricitinib have been approved for the treatment RA patients who inadequately respond to methotrexate or anti-tumor necrosis factor drugs. The aim of this narrative review is to summarize the data concerning the drugs' basic mechanisms and clinical trial results in order to inform clinicians about the serious and non-serious adverse events associated with JAK inhibitors. Areas covered: The mechanisms, adverse events, and clinical trial data associated with the use of JAK inhibitors in RA patients were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1999 and April 2018 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: Management of the adverse events of JAK inhibitors is challenging because of the lack of robust treatment data used and the heterogeneity of the events themselves. Treatment decisions are often made clinically on the basis of age and the burden of comorbidities, and require the multidisciplinary collaboration of rheumatologists and other specialists.
29477035 Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis 2018 Apr BACKGROUND: Previously, we have demonstrated that kynurenic acid (KYNA), an endogenous metabolite of tryptophan formed along kynurenine pathway, is present in synovial fluid of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In this study, the goal was to investigate the presence of quinaldic acid (QUDA), a putative metabolite of KYNA, in synovial fluid of RA and OA patients. METHODS: The effect of QUDA on proliferation and motility of synovial fibroblasts and its interaction with KYNA were determined in vitro. The study was conducted on synovial fluid obtained from 38 patients with RA and 15 patients with OA. QUDA was identified and quantified using the gas chromatography-mass spectrometry (GC-MS) method. In vitro experiments were conducted on rabbit synoviocyte cell line HIG-82. RESULTS: Presence of QUDA was detected in all 53 samples of synovial fluid. The concentration of QUDA in synovial fluid obtained from patients with RA was 28.6 ± 14.9 pmol/ml, which was lower in comparison with OA 42.3 ± 10.0 pmol/ml. QUDA content positively correlated with the number of tender joints and negatively with the total cell counts determined in synovial fluid of RA patients. It did not correlate with KYNA content. QUDA reduced both proliferation and motility of synoviocytes in a dose-dependent manner. The enhancement of antiproliferative action of QUDA by KYNA was evidenced. CONCLUSIONS: Data show a local deficit of QUDA in RA patients and suggest its potential role as an endogenous substance controlling synoviocyte viability.
28681148 Effects of denosumab treatment on bone mineral density and joint destruction in patients w 2018 Jul We aimed to investigate the efficacy of denosumab for rheumatoid arthritis (RA). This study enrolled 70 RA patients who received denosumab 60 mg subcutaneous injection at baseline and at 6 months. Bone mineral densities (BMD) of the lumbar spine, total hip, femoral neck, and hand were measured by dual energy X-ray absorptiometry. Changes in total modified Sharp score (mTSS), erosion (EN) score, and joint space narrowing score at baseline from 12 months before and at 12 months from baseline. The mean values of BMD of the lumbar spine, total hip, femoral neck, and hand significantly increased by 7.3, 4.7, 3.9, and 5.4%, respectively, at 12 months. At 12 months from baseline, there were significant decreases in the values of mTSS (1.13 vs. 0.59; p = 0.002) and EN score (0.40 vs. 0.07; p < 0.001), compared with the values at baseline from 12 months before. The existing combined modality therapy with denosumab might be effective for osteoporosis and joint destruction in patients with RA.
30557668 Alpha-mangostin: Anti-inflammatory and antioxidant effects on established collagen-induced 2019 Feb Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.
29533756 Comprehensive evaluation of finger flexor tendon entheseal soft tissue and bone changes by 2018 Sep OBJECTIVES: To determine whether a detailed sonographic evaluation of the hand flexor tendon compartment could help differentiate between psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Thirty-seven patients with PsA, 47 with RA and 10 healthy controls (HC) had flexor tendon (FT) compartment imaging of the dominant hand 2nd to 4th tendons using grey scale (GS) and power Doppler (PD) ultrasound (US) with evaluation for tenosynovitis, peri-tendinous lesions, soft tissue oedema and bony changes at FT insertions. 24/37 PsA and 19/47 RA cases had morning stiffness and 19/37 PsA and 10/47 RA had swollen and/or tender fingers. RESULTS: Tenosynovitis was more common in PsA (25/37) despite higher DAS28 scores in RA (25/37 versus 10/45; p<0.001). Peri-tendinous dermal soft tissue oedema with associated PD signal was evident in one third of PsA patients but in no RA patients (p=0.003). Flexor tendon enthesopathy including new bone formation at the insertional site was significantly more common in PsA (p=0.001). Considering a total inflammatory score per patient summing up the three modifications of the flexor tendon (tenosynovitis, peri-tendinous oedema and insertional enthesophytes) the difference between PsA and RA remained statistically significant (p<0.001). CONCLUSIONS: Our study adds to the growing body of literature that high resolution US of the hand FT compartment may help differentiate between RA and PsA, which needs assessment in the diagnostic setting.
30531041 Two atypical presentations of lepra reactions. 2018 Oct Leprosy or Hansen's disease is a chronic infectious granulomatous disease with varied presentation, especially in the setting of lepra reactions. We report two such atypical presentations each of Type I and Type II Lepra reactions; the first being an elderly male presenting with fever, while the second case being of a young boy being evaluated for cervical lymphadenitis.
29520264 Monomeric C-Reactive Protein Binds and Neutralizes Receptor Activator of NF-κB Ligand-Ind 2018 C-reactive protein (CRP) is an established marker of rheumatoid arthritis (RA) but with ill-defined actions in the pathogenesis. Here, we show that CRP regulates the differentiation of osteoclasts, a central mediator of joint inflammation and bone erosion in RA, in a conformation- and receptor activator of NF-κB ligand (RANKL)-dependent manner. CRP in the native conformation is ineffective, whereas the monomeric conformation (mCRP) actively modulates osteoclast differentiation through NF-κB and phospholipase C signaling. Moreover, mCRP can bind RANKL, the major driver of osteoclast differentiation, and abrogate its activities. The binding and inhibition of RANKL are mediated by the cholesterol binding sequence (CBS) of mCRP. Corroborating the in vitro results, CRP knockout exacerbates LPS-induced bone resorption in mice. These results suggest that mCRP may be protective in joint inflammation by inhibiting pathological osteoclast differentiation and that the CBS peptide could be exploited as a potential RANKL inhibitor.
30595458 Safety and Survival Associated with Biologic Therapies: First Report of the Biobadaguay on 2020 Sep OBJECTIVE: Analyze adverse events (AE) and survival associated with biologic therapies (BT) in the Biobadaguay, the Paraguayan Uruguayan registry of adverse events. METHODS: Prospective, observational study of undetermined duration. Patients on BT at initiation and controls were included. Clinical, biological and treatment variables were registered. RESULTS: A total of 826 registers were entered (650 BT and 176 controls); 70.9% were women and rheumatoid arthritis (RA) was the most frequent diagnosis (63.2%). The BT most often used was adalimumab and the main cause of discontinuation was loss of efficacy (42.1%). The incidence of AE of patients on BT was 143.9 (128.8-160.8) per 1000 patients/year. In the comparative study of AE related to diagnosis, juvenile idiopathic arthrosis (JIA) was associated with a higher overall number of AE (RTI = 2.3; 95%CI: 1.6-3.4; P = 4.27 ×10(-6)), whereas RA was associated with a higher number of serious AE (RTI = 2.2; 95% CI: 1.2-4.1; P =1.17 ×10(-2)). On the other hand, treatment with tocilizumab was associated with a higher rate of AE (RTI = 2.69; 95% CI: 1.9-3.82; P = 3.13 ×10(-8)). In JIA, treatment with corticosteroids and number of previous BT was associated with a decrease in BT survival. CONCLUSION: In this first report of the Biobadaguay registry, the main cause of BT discontinuation was loss of efficacy. In terms of the diagnosis involved, RA and JIA were associated with a higher risk of AE. In this registry, variables related to a shorter survival of BT were identified.
27321430 Intensive immunosuppressive therapy for endogenous lipoid pneumonia associated with rheuma 2018 Nov Endogenous lipoid pneumonia is an uncommon inflammatory pulmonary disease that is caused by lipids from an endogenous source, the treatment for which has not been established. We report the first case of endogenous lipoid pneumonia presenting as lung consolidation and which was associated with rheumatoid arthritis. Treatment was successful with intensive immunosuppressive therapy. When a physician finds lung consolidation in a patient with active rheumatic disease, lipoid pneumonia should be considered.
29671403 KDiamend: a package for detecting key drivers in a molecular ecological network of disease 2018 Apr 11 BACKGROUND: Microbial abundance profiles are applied widely to understand diseases from the aspect of microbial communities. By investigating the abundance associations of species or genes, we can construct molecular ecological networks (MENs). The MENs are often constructed by calculating the Pearson correlation coefficient (PCC) between genes. In this work, we also applied multimodal mutual information (MMI) to construct MENs. The members which drive the concerned MENs are referred to as key drivers. RESULTS: We proposed a novel method to detect the key drivers. First, we partitioned the MEN into subnetworks. Then we identified the most pertinent subnetworks to the disease by measuring the correlation between the abundance pattern and the delegated phenotype-the variable representing the disease phenotypes. Last, for each identified subnetwork, we detected the key driver by PageRank. We developed a package named KDiamend and applied it to the gut and oral microbial data to detect key drivers for Type 2 diabetes (T2D) and Rheumatoid Arthritis (RA). We detected six T2D-relevant subnetworks and three key drivers of them are related to the carbohydrate metabolic process. In addition, we detected nine subnetworks related to RA, a disease caused by compromised immune systems. The extracted subnetworks include InterPro matches (IPRs) concerned with immunoglobulin, Sporulation, biofilm, Flaviviruses, bacteriophage, etc., while the development of biofilms is regarded as one of the drivers of persistent infections. CONCLUSION: KDiamend is feasible to detect key drivers and offers insights to uncover the development of diseases. The package is freely available at http://www.deepomics.org/pipelines/3DCD6955FEF2E64A/ .
29502174 Baricitinib for Previously Treated Moderate or Severe Rheumatoid Arthritis: An Evidence Re 2018 Jul As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer (Eli Lilly) of baricitinib (BARI; Olumiant(®); a Janus kinase inhibitor that is taken orally) to submit evidence of its clinical and cost effectiveness for the treatment of moderate to severe rheumatoid arthritis (RA) after the failure of disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission (CS) to NICE. The clinical-effectiveness evidence in the CS for BARI was based predominantly on three randomised controlled trials comparing the efficacy of BARI against adalimumab or placebo, as well as one long-term extension study. The clinical-effectiveness review identified no head-to-head evidence on the efficacy of BARI against all the comparators within the scope. Therefore, the company performed network meta-analyses (NMAs) in two different populations: one in patients who had experienced an inadequate response to conventional DMARDs (cDMARD-IR), and the other in patients who had experienced an inadequate response to tumour necrosis factor inhibitors (TNFi-IR). The company's NMAs concluded BARI had comparable efficacy as the majority of its comparators in both populations. The company submitted a de novo discrete event simulation model that analysed the incremental cost-effectiveness of BARI versus its comparators for the treatment of RA from the perspective of the National Health Service (NHS) in four different populations: (1) cDMARD-IR patients with moderate RA, defined as a 28-Joint Disease Activity Score (DAS28) > 3.2 and no more than 5.1; (2) cDMARD-IR patients with severe RA (defined as a DAS28 > 5.1); (3) TNFi-IR patients with severe RA for whom rituximab (RTX) was eligible; and (4) TNFi-IR patients with severe RA for whom RTX in combination with methotrexate (MTX) is contraindicated or not tolerated. In the cDMARD-IR population with moderate RA, the deterministic incremental cost-effectiveness ratio (ICER) for BARI in combination with MTX compared with intensive cDMARDs was estimated to be £37,420 per quality-adjusted life-year (QALY) gained. In the cDMARD-IR population with severe RA, BARI in combination with MTX dominated all comparators except for certolizumab pegol (CTZ) in combination with MTX, with the ICER of CTZ in combination with MTX compared with BARI in combination with MTX estimated to be £18,400 per QALY gained. In the TNFi-IR population with severe RA, when RTX in combination with MTX was an option, BARI in combination with MTX was dominated by RTX in combination with MTX. In the TNFi-IR population with severe RA for whom RTX in combination with MTX is contraindicated or not tolerated, BARI in combination with MTX dominated golimumab in combination with MTX and was less effective and less expensive than the remaining comparators. Following a critique of the model, the ERG undertook exploratory analyses after applying corrections to the methods used in the NMAs and two programming errors in the economic model that affected the company's probabilistic sensitivity analysis (PSA) results. The ERG's NMA results were broadly comparable with the company's results. The programming error that affected the PSA of the severe cDMARD-IR population had only a minimal impact on the results, while the error affecting the severe TNFi-IR RTX-ineligible population resulted in markedly higher costs and QALYs gained for the affected comparators but did not substantially modify the conclusions of the analysis. The NICE Appraisal Committee concluded that BARI in combination with MTX or as monotherapy is a cost-effective use of NHS resources in patients with severe RA, except in TNFi-IR patients who are RTX-eligible.
28993952 Discordance of the Framingham cardiovascular risk score and the 2013 American College of C 2018 Feb Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African-American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores.
29678183 A randomized controlled cross-over trial investigating the effect of anti-inflammatory die 2018 Apr 20 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. METHODS: In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2 × 10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. DISCUSSION: The nutritional status of patients with RA often is poor and many ask their physician for diet advice. No evidence-based dietary guidelines for patients with RA exist because of the paucity of well-conducted sufficiently large diet intervention trials. ADIRA is an efficacy study and will provide evidence as to whether dietary treatment of RA can reduce disease activity and improve quality of life as well as reduce individual and societal costs. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT02941055 .
27180974 Pneumocystis jirovecii pneumonia developed in a patient with rheumatoid arthritis after 14 2018 Nov A 66-year-old woman who had rheumatoid arthritis and underwent a long-term treatment with methotrexate and etanercept developed Pneumocystis jirovecii pneumonia (PCP) 3 months after iguratimod add-on. Although most rheumatologists might have the impression that iguratimod has less toxicity and immunosuppressive effect compared with methotrexate and biologic disease-modifying antirheumatic drugs, this case suggests that iguratimod may increase the risk of PCP, especially in combination with other drugs.
29741136 Mortality and its predictors in patients with rheumatoid arthritis: a Danish population-ba 2018 Sep OBJECTIVES: To investigate mortality and its predictors in a retrospectively defined population-based rheumatoid arthritis (RA) inception cohort Method: We included patients ascertained with incident RA from a region in the southern part of Denmark from 1995 to 2002. All patients fulfilled the 1987 American College of Rheumatology criteria for RA. The patients were followed from RA classification until death, emigration, or end of follow-up on 31 December 2013. We used personal record linkage with national public registers to obtain information on education, employment, cohabitation, comorbidity, and vital status. RESULTS: The cohort comprised 509 patients, of whom 200 (39%) died during 6079 person-years. The most frequent underlying causes of death were cardiovascular disease (34%), neoplasms (26%), and respiratory disease (12%). In rheumatoid factor (RF)-positive males, the standardized mortality ratio (95% confidence interval) from all causes was 1.47 (1.15-1.88), from cardiovascular disease 1.63 (1.09-2.46), from respiratory disease 2.03 (1.06-3.90), and from neoplasms 2.26 (1.02-5.03) in the age group < 70 years, and 2.45 (1.23-4.90) in the age group > 79 years. On applying Cox models after multiple imputations by chained equations, we found that RF modified the effect of age. Employment status, comorbidity, and gender were independent baseline predictors of subsequent mortality. CONCLUSION: In this cohort, significant excess mortality was confined to RF-positive males. The effect of age was modified by RF, and employment status and comorbidity were independent predictors of mortality.
30010899 The patient perspective on biologic DMARD dose reduction in rheumatoid arthritis: a mixed 2018 Nov 1 OBJECTIVES: The aim of this study was to identify the factors that play a role for patients with RA when considering dose reduction (i.e. gradual tapering until discontinuation) of biological DMARDs (bDMARDs), and to determine their relative importance. METHODS: A mixed methods design was used in which we identified influencing factors by performing semi-structured interviews and ranked these factors using a Maximum Difference Scaling questionnaire. Also, we looked at the influence of several patient characteristics on this ranking. RESULTS: For sub study 1 and 2, 22 and 192 patients with RA were included, respectively, in the analyses. Thirty factors were identified from the interviews-characterized into nine themes-and appraised in the questionnaire. Most respondents had a positive attitude towards bDMARD dose reduction. The study showed that patients are concerned that dose reduction will lead to a disease flare that affects their daily life (pain, function). It is important for them to know that it is possible to increase the dose if (further) reduction fails and that the bDMARD will be effective again. Patients value the opinion of their rheumatologist, and being involved in the decision to start tapering is highly ranked as well. The most important factors were consistent between different groups of patients. CONCLUSION: The results from this study facilitate implementation of bDMARD dose reduction; they inform care providers on what is important for patients and provide a basis for shared decision making.
29329557 One-year risk of serious infection in patients treated with certolizumab pegol as compared 2018 Jan 2 BACKGROUND: Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias. METHODS: Patients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching. RESULTS: Patients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups.
30190721 T Cells That Help B Cells in Chronically Inflamed Tissues. 2018 Chronically inflamed tissues commonly accrue lymphocyte aggregates that facilitate local T cell-B cell interactions. These aggregates can range from small, loosely arranged lymphocyte clusters to large, organized ectopic lymphoid structures. In some cases, ectopic lymphoid structures develop germinal centers that house prototypical T follicular helper (Tfh) cells with high expression of Bcl6, CXCR5, PD-1, and ICOS. However, in many chronically inflamed tissues, the T cells that interact with B cells show substantial differences from Tfh cells in their surface phenotypes, migratory capacity, and transcriptional regulation. This review discusses observations from multiple diseases and models in which tissue-infiltrating T cells produce factors associated with B cell help, including IL-21 and the B cell chemoattractant CXCL13, yet vary dramatically in their resemblance to Tfh cells. Particular attention is given to the PD-1(hi) CXCR5(-) Bcl6(low) T peripheral helper (Tph) cell population in rheumatoid arthritis, which infiltrates inflamed synovium through expression of chemokine receptors such as CCR2 and augments synovial B cell responses via CXCL13 and IL-21. The factors that regulate CD4(+) T cell production of CXCL13 and IL-21 in these settings are also discussed. Understanding the range of T cell populations that can provide help to B cells within chronically inflamed tissues is essential to recognize these cells in diverse inflammatory conditions and to optimize either broad or selective therapeutic targeting of B cell-helper T cells.