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ID PMID Title PublicationDate abstract
29858236 Effectiveness, Complications, and Costs of Rheumatoid Arthritis Treatment with Biologics i 2018 Oct OBJECTIVE: To examine clinical effectiveness, treatment complications, and healthcare costs for indigenous and non-indigenous Albertans with rheumatoid arthritis (RA) participating in the Alberta Biologics Pharmacosurveillance program. METHODS: Patients initiating biologic therapy in Alberta (2004-2012) were characterized for disease severity and treatment response. Provincial hospitalization separations, physician claims, outpatient department data, and emergency department data were used to estimate treatment complication event rates and healthcare costs. RESULTS: Indigenous patients (n = 90) presented with higher disease activity [mean 28-joint count Disease Activity Score (DAS28) 6.11] than non-indigenous patients (n = 1400, mean DAS28 5.19, p < 0.0001). Improvements in DAS28, function, swollen joint count, CRP, and patient and physician global evaluation scores were comparable to non-indigenous patients, but indigenous patients did not have a significant improvement in erythrocyte sedimentation rate (-0.31 per month, 95% CI -0.79 to 0.16, p = 0.199). At the end of study followup, 13% (12/90) of indigenous and 33% (455/1400) of non-indigenous patients were in DAS28 remission (p < 0.001). Indigenous patients had a 40% increased risk of all-cause hospitalization [adjusted incidence rate ratio (IRR) 1.4, 95% CI 1.1-1.8, p = 0.01] and a 4-fold increase in serious infection rate (adjusted IRR 4.0, 95% CI 2.3-7.0, p < 0.001). Non-indigenous patients incurred higher costs for RA-related hospitalizations (difference $896, 95% CI 520-1273, p < 0.001), and outpatient department visits (difference $128, 95% CI 2-255, p = 0.047). CONCLUSION: We identified disparities in treatment outcomes, safety profiles, and patient-experienced effects of RA for the indigenous population in Alberta. These disparities are critical to address to facilitate and achieve desired RA outcomes from individual and population perspectives.
29352843 Tocilizumab after a first-line with anti-TNF in rheumatoid arthritis: a cost-consequence a 2018 May OBJECTIVES: Switching to a different mechanism of action in rheumatoid arthritis (RA) patients after a first anti-TNF-α has proved to be effective. The objective of this study was a health economic assessment in Italy. METHODS: The study was conducted using a pharmacoeconomic model with a 3-year time horizon. Effectiveness was measured as days gained in low disease activity (LDA; DAS28-ESR <3.2) or in remission (DAS28-ESR <2.6). The model simulated the response to treatments, based on the Rotation Or Change (ROC) trial, the probability of discontinuation and switch to a 3rd-line biologic, and the transition to death. Time on treatment curves for 2nd-line biologics were derived from published Italian real-word data. Costs were estimated based on published sources and Italian prices and tariffs. RESULTS: The switch to tocilizumab after the failure of a first anti-TNF-α was more effective than a second anti-TNF-α, in terms of days in remission (224 vs. 114 days) and of days in LDA (345 vs. 193 days). The cost-consequence ratio with tocilizumab iv was 174 euros/day in remission and 113 euros/day in LDA. With tocilizumab sc the ratio was 181 euros/day in remission and 117 euros/day in LDA. The same ratios for the anti-TNF-α treatments ranged from 233 to Euro 320 euros per day in remission and from 138 to 190 euros per day in LDA. CONCLUSIONS: The switch to a different mechanism of action, namely tocilizumab, after the failure of a first anti-TNF-α agent seems a rational strategy for RA patients in the Italian setting.
29022053 Glycated albumin (GA) and inflammation: role of GA as a potential marker of inflammation. 2018 Jan AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. METHODS: We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators. Glycated albumin and specific inflammatory mediators have been reported to play various roles in the pathogenesis of insulin resistance, atherosclerosis, coronary artery disease, retinopathy, and nephropathy. In the case of nephropathy and recently retinopathy, there is considerable evidence for GA in concert with inflammation playing a direct role in organ pathology. There is copious literature detailing GA's involvement in stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent clinical study has shown GA to be a marker for inflammation in non-diabetic rheumatoid arthritis patients with the significance of standard inflammatory markers. CONCLUSIONS: The clinical utility of GA measurement may likely reside in its versatility as both a mediator of inflammation as well as a marker to track hyperglycemia and other diabetes complications. Further understanding of the role GA plays in glycemic and inflammatory diseases could lead to its acceptance as an independent bio-inflammatory marker.
29982781 Physiological effects of modulating the interleukin-6 axis. 2018 Feb 1 IL-6 is a pleiotropic cytokine involved in many biological functions that affect tissues beyond the immune system and the vasculature. This multifunctional cytokine exerts its actions via the classic signalling pathway when it binds to the transmembrane IL-6 receptor (IL-6R) or via the trans-signalling pathway upon binding to the soluble form of IL-6R (sIL-6R). In general, classic IL-6 signalling is responsible for the anti-inflammatory properties of IL-6, whereas trans-signalling is responsible for the pro-inflammatory actions of IL-6. As a result, dysregulation of the IL-6 axis can lead to the onset or development of several disease states, particularly autoimmune and inflammatory disorders, including RA and GCA. This pathological role of IL-6 means that pharmacologic modulation of the IL-6 axis is a rational therapeutic approach; however, multiple predictable, but often underappreciated, effects on tissues and organs beyond the blood vessels may also occur.
30413925 Bulgarian rheumatology: science and practice in a cost-constrained environment. 2019 Mar Our aim was to appraise publications from Bulgaria, to assess their global impact, and to describe features and challenges unique to the rheumatology practice in Bulgaria characterized by stringent cost constraints. The Scopus database was queried on 25th July 2018 and data on the number of published documents, their Hirsch-indices and citations number were extracted. Published Bulgarian guidelines for the management of rheumatic diseases and the presented data on Bulgarian Rheumatology Society were identified based on prior knowledge of the authors. From all the identified 1082 document the most extensively researched areas were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoporosis, and osteoarthritis (OA). For the last five years (from Jan 2013 to 25th July 2018) the number of publications was 293. We found that Bulgaria's international scientific collaboration in the field of rheumatology is focused on a handful of countries mainly from Europe. Although Bulgarian rheumatologists have access to costly biologic agents for treating their patients with rheumatic diseases, their funding may not be granted according to the current recommendations of European League against Rheumatism (EULAR) and national guidelines for the management of rheumatic diseases. Although the western world clearly dominates the production of scientific publications in rheumatology, Bulgarian rheumatology may present another perspective for diagnosis and management of patients with rheumatic diseases in a cost-stringent environment. Nevertheless, both rheumatology science and practice in Bulgaria still have a long way to go to take its deserved place among the other European countries.
28736271 B cells and their cytokine activities implications in human diseases. 2018 Jan B cells are the only cell type that can give rise to antibody-producing cells, and the only cell type whose selective depletion can, today, lead to an improvement of a wide range of immune-mediated inflammatory diseases, including disorders not primarily driven by autoantibodies. Here, I discuss this paradoxical observation, and propose that the capacity of B cells to act as cytokine-producing cells explains how they can control monocyte activity and subsequently disease pathogenesis. Together with current data on the effect of anti-CD20 B cell-depleting reagents in the clinic, this novel knowledge on B cell heterogeneity opens the way for novel safer and more efficient strategies to target B cells. The forthcoming identification of disease-relevant B cell subsets is awaited to permit their monitoring and specific targeting in a personalized medicine approach.
28302406 Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-co 2018 Apr The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B(2) and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.
30021126 Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporos 2018 Nov INTRODUCTION: Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies. METHODS: Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. RESULTS: The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. CONCLUSIONS: Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.
30426384 Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in t 2019 Feb Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.
29482039 A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican 2018 Apr BACKGROUND AND AIMS: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). METHODS: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. RESULTS: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10(-4)) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (β ± SE = -0.84 ± 0.18, p = 3.80 × 10(-6)). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, β ± SE = -0.28 ± 0.06, p = 5.11 × 10(-6)). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10(-6)) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10(-5)) in EAs. CONCLUSIONS: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.
30299248 Serum calprotectin as a marker of ultrasound-detected synovitis in early psoriatic and rhe 2019 May OBJECTIVES: We aimed to evaluate the correlation between serum calprotectin and clinical and ultrasonographic (US) variables in early-onset psoriatic arthritis (PsA) and controls with rheumatoid arthritis (RA). METHODS: In a retrospective cross-sectional study, including PsA and matched RA patients, 44 joint counts (TJC, SJC), calprotectin, ESR and CRP were measured. US of wrists and MCPs 1-5 was performed, with grey-scale (GS) and power Doppler (PD) scored 0-3 at each site, summed in a total score. The correlation between calprotectin, clinical and US variables was evaluated by Spearman's coefficient, the predictivity by calprotectin of US by regression. Secondary analyses separating polyarticular PsA and using different US definitions (GS>1, PD>1) were performed. RESULTS: 78 PsA and 78 RA were included (PsA male 32%; mean age 51.7 (13.5)). Calprotectin did not significantly differ in PsA and RA. In PsA, calprotectin correlated with GS score (ρ=0.340, p=0.008), PD score (ρ=0.292, p=0.023) and the presence of PD (ρ=0.263, p=0.042); in RA there were no significant correlations. In polyarticular PsA, a significant correlation between calprotectin and GS (ρ=0.369, p=0.019) and PD scores (ρ=0.363, p=0.021) was confirmed. In both PsA and RA, calprotectin and CRP significantly correlated, while SJC and TJC did not. In the regression analysis, calprotectin did not predict US variables in PsA. Similar results were achieved in RA. CONCLUSIONS: In early PsA, serum calprotectin correlates with US measures of disease activity. Our results provide preliminary evidence for the application of this biomarker in early PsA.
29364523 Population Pharmacokinetics of the TNF-α and IL-17A Dual-Variable Domain Antibody ABT-122 2018 Jun ABT-122 is an IgG1 dual-variable domain immunoglobulin that specifically blocks TNF-α and IL-17A. This work characterized ABT-122 pharmacokinetics using nonlinear mixed-effects modeling and ABT-122 serum concentrations from 72 healthy subjects, 196 subjects with rheumatoid arthritis (RA), and 144 subjects with psoriatic arthritis (PsA) enrolled in 4 phase 1 and 2 phase 2 studies (0.1-10 mg/kg intravenously and 0.3-3 mg/kg subcutaneous single doses and 0.3-3.0 mg/kg subcutaneous and 60-240 mg subcutaneous doses weekly or every other week). A 2-compartment model with a combination of linear clearance (0.419 L/day) and nonlinear clearance (relevant only at low doses; V(max) and K(m) of 0.155 mg/day and 0.0458 mg/L, respectively) described ABT-122 pharmacokinetics. Subcutaneous bioavailability was 35%-58% across formulations and populations. Body weight was a significant covariate for ABT-122 clearance, with subjects with body weight of 140 and 40 kg estimated to have 38% lower and 43% higher ABT-122 AUC, respectively, compared with a 70-kg reference subject. ABT-122 antidrug antibody (ADA) titer (ADA incidence, 47%; 0 to 519 000 titer range in the data set) was a continuous covariate on ABT-122 clearance. An ADA titer of 100 units resulted in a 5-fold increase in clearance. Sex, age, and baseline serum albumin or baseline C-reactive protein level did not impact ABT-122 exposure. Fixed-effects and random-effects parameters were estimated with a relative standard error of ≤17% and ≤28%, respectively, and the model was qualified using bootstrap analysis and visual predictive checks. This analysis characterized ABT-122 exposure across populations and supported exposure-response analyses of ABT-122 efficacy in RA and PsA.
29278951 Calprotectin (S100A8/A9) should preferably be measured in EDTA-plasma; results from a long 2018 Feb Calprotectin (S100A8/A9), a protein expressed in neutrophils and monocytes/macrophages in circulation and inflamed tissue, is associated with measures of disease activity in rheumatoid arthritis (RA) patients both when measured in ethylenediaminetetraacetic acid (EDTA)-plasma and in serum. We wanted to explore if EDTA-plasma or serum should be preferred for calprotectin as a marker of disease activity. Calprotectin was analysed in EDTA-plasma and serum by enzyme-linked immunosorbent assay (ELISA) at baseline in 141 RA patients, starting biologic disease-modifying anti-rheumatic drugs (bDMARDs), and after three months. Differences between plasma and serum levels of calprotectin were assessed by Wilcoxon signed rank test. Variability was assessed by quartile coefficient of dispersion. Spearman's test explored correlations between calprotectin in plasma and serum and between calprotectin (plasma or serum) and clinical/ultrasound (US) measures of disease activity. Bland Altman plots were used for method comparisons. Conventional inflammatory markers were evaluated for comparison. Calprotectin had similar variability when measured in plasma and serum, but there was a significant difference in concentrations between plasma and serum (p < .001). The correlation coefficients at baseline between calprotectin measured in plasma/serum and measures of disease activity were r(s) = 0.62/0.46 for sum power Doppler score (PD), r(s) = 0.60/0.48 for assessor's global visual analogue scale (VAS), r(s) = 0.59/0.43 for sum grey scale (GS) score and r(s) = 0.47/0.37 for swollen joint count of 32, all p < .001. Similar differences were found after three months. Calprotectin measured in plasma showed the strongest associations with assessments of disease activity, and EDTA-plasma should preferably be used when evaluating disease activity in RA patients.
28622048 A randomized, double-blind, parallel-group, phase III study of shortening the dosing inter 2018 Jan OBJECTIVE: To determine the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) monotherapy every week (qw) versus every other week (q2w) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC q2w. METHODS: Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162 mg qw monotherapy or TCZ-SC 162 mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed. RESULTS: TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was -1.21 (95%CI: -2.13, -0.30, p = .0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw. CONCLUSIONS: In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.
29471516 Optical spectral transmission to assess inflammation in hand and wrist joints of rheumatoi 2018 May 1 OBJECTIVE: To develop an optical spectral transmission (OST) model to measure joint inflammation, and thus disease activity, as well as to evaluate (patho-)physiological findings that could lead to misclassification of inflammation. METHODS: Forty-six RA patients were included in this cross-sectional study, where US scores, duplicate OST measurements and 28-joint DAS (DAS28) were acquired. With US as a reference standard, the diagnostic performance of OST in detecting inflammation at the joint level was evaluated using receiver operating characteristic (ROC) curve analyses. At the patient level, correlations with US were analysed for DAS28 and OST, and at joint level for OST and tender and swollen joint counts (TJC and SJC, respectively). Joint pathology potentially influencing misclassification by OST [erosions, osteophytes, tendon (sheath) inflammation (ab)normal vasculature and chondrocalcinosis] was evaluated for significance in a multivariate nominal logistic regression model. RESULTS: Diagnostic performance of OST was good for MCP [area under the ROC curve (AUC-ROC) 0.88], PIP (AUC-ROC 0.83) and wrist (AUC-ROC 0.74) joints and for all joints together (AUC-ROC 0.85). At the patient level, DAS28 correlated very poorly (ρ = 0.06) and OST moderately (ρ = 0.54) with US. At the joint level, US correlation with OST was strong (ρ = 0.64), with SJC it was weak (ρ = 0.30) and with TJC it was very weak (ρ = -0.02). Misclassification of inflammation by OST was relatively rare (17%). Dorsal erosions [odds ratio (OR) 4.0], osteophytes (OR 2.1) and extensor tendinitis (OR 4.6) increased the risk of underestimating inflammation of MCP and PIP joints and osteophytes (OR 3.0) also increased the risk of overestimating inflammation. CONCLUSION: OST is a sensitive, specific and objective technique to assess joints inflammation of the hands and wrists of RA patients, even though bone and tendon pathology increases the risk of misclassification.
30429434 Methotrexate-associated Lymphoproliferative Disorder of the Stomach Presumed to Be Mucosa- 2018 The number of patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) is increasing. We describe a case of MTX-LPD of the stomach. After treatment with methotrexate for rheumatoid arthritis, the patient developed left cervical lymphadenopathy and an ulcerative lesion in the stomach, which was presumed to be a mucosa-associated lymphoid tissue (MALT) lymphoma. However, we suspected MTX-LPD, based on the clinical course and the positivity of in situ hybridization for the detection of the Epstein-Barr encoding region. After the cessation of MTX, the left cervical lymphadenopathy and the gastric lesion disappeared. This is first report of gastric MTX-LPD that was presumed to be MALT lymphoma.
30171335 Rheumatoid arthritis in remission : Decreased myostatin and increased serum levels of peri 2019 Jan BACKGROUND: Chronic inflammation of rheumatoid arthritis (RA) is associated with disturbances in muscle and bone metabolism. AIM: The purpose of this study was to investigate whether endocrine regulators of myogenesis and bone metabolism in patients with rheumatoid arthritis (RA) in remission differed from unaffected healthy controls. An additional point was whether these were associated with patients' health-related functioning or particular bodily functions of the International Classification of Functioning, Disability and Health (ICF). METHODS: Bone turnover and the markers for muscle, i.e. myostatin (MSTN), follistatin (FSTN), growth differentiation factor (GDF-15) and for bone, i.e. sclerostin (SOST), dickkopf 1 (Dkk1), periostin (PSTN) metabolism were determined in 24 female RA patients and matched healthy controls. The chair rising test (CRT), timed up and go test (TUG), 6 min walking test, maximum hand grip and back extensor strength tests were used to assess patients' health-related functions. Additionally, bone mineral density of the lumbar spine and the hip region was measured. RESULTS: For the bone turnover markers no differences were observed between patients and controls. In contrast, the markers MSTN and Dkk1 were significantly lower and FSTN and PSTN significantly higher in patients than controls. Patients performed worse in the CRT and TUG. Some correlations reflected associations between these endocrine factors and physical function. CONCLUSION: Anti-inflammatory therapy may be responsible for the positive effect on endocrine factors influencing myogenesis. Elevation of PSTN probably reflects the increased risk of fragility fractures in RA patients.
29368188 The nocebo effect challenges the non-medical infliximab switch in practice. 2018 May BACKGROUND: In clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of "first do no harm" may be challenged in a patient when switching from originator to biosimilar biological. AIM: To describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring. METHODS: Inflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching. RESULTS: After inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn's disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications. CONCLUSIONS: In inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.
28695605 Returns to scientific publications for pharmaceutical products in the United States. 2018 Feb Drug-specific clinical and health economic and outcomes research (HEOR) publications have amassed, but their effect on drug sales is largely unknown. We estimated the impact of publications on pharmaceutical sales in 3 markets (statins, rheumatoid arthritis, and asthma drugs) with varying generic competition. An event-study approach with fixed effects and difference-in-fixed-effects modeling was used to estimate the causal effects of drug-specific publications on subsequent quarter's drug-specific sales and volume. High-impact clinical and HEOR publications have significant positive effects on sales (mediated through price) and volume in the statin market (high generic competition). High-impact clinical publications have a significant positive effect on sales (mediated through volume) in low-generic competition market (asthma). The effects of publications in the rheumatoid arthritis market (no generic competition) on sales were null. Manufacturers' investment in clinical and HEOR publications needs to be strategic and should be anticipated and complemented by public investments in such studies.
29589061 Overview of Osteoimmunology. 2018 May Aberrant or prolonged immune responses often affect bone metabolism. The investigation on bone destruction observed in autoimmune arthritis contributed to the development of research area on effect of the immune system on bone. A number of reports on bone phenotypes of immunocompromised mice indicate that the immune and skeletal systems share various molecules, including transcription factors, signaling molecules, and membrane receptors, suggesting the interplay between the two systems. Furthermore, much attention has been paid to the modulation of immune cells, including hematopoietic progenitor cells, by bone cells in the bone marrow. Thus, osteoimmunology which deals with the crosstalk and shared mechanisms of the bone and immune systems became the conceptual framework fundamental to a proper understanding of both systems and the development of new therapeutic strategies.