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ID PMID Title PublicationDate abstract
29347932 Epidemiology of arthritis, chronic back pain, gout, osteoporosis, spondyloarthropathies an 2018 Jan 18 BACKGROUND: Previous estimates for the prevalence of musculoskeletal conditions (MSK) and chronic pain in Australia have been based on self-report. We aimed to determine the prevalence and distribution of arthritis, chronic back pain, gout, osteoporosis, spondyloarthropathies and rheumatoid arthritis and current consultations for chronic pain among adults attending Australian general practice, and describe their distribution according to sociodemographic characteristics and presence of co-morbidities. METHODS: We investigated 1,501,267 active adult patients (57.6% females; 22.5% ≥65y) evaluated between 2013 and 2016 and included in the MedicineInsight database (a National Prescribing Service MedicineWise program), a large general practice data program that extracts longitudinal de-identified electronic medical record data from 'active' patients in over 550 practices. Three main groups of outcomes were investigated: 1) "prevalence" of arthritis, chronic back pain, gout, osteoporosis, spondyloarthropathies, and/or rheumatoid arthritis between 2000 and 2016; 2) "current" diagnosis/encounter for the same conditions occurring between 2013 and 2016, and; 3) "current" consultations for chronic pain of any type occurring between 2013 and 2016. RESULTS: The combined "prevalence" of the investigated MSK (diagnosis between 2000 and 2016) among adults attending Australian general practice was 16.8% (95%CI 15.9;17.7) with 21.3% (95%CI 20.2;22.4) of the sample consulting for chronic pain between 2013 and 2016. The investigated MSK with the highest "prevalence" were arthritis (9.5%) and chronic back pain (6.7%). Patients with some of these MSK attended general practices more frequently than those without these conditions (median 2.0 and 1.0 contacts/year, respectively). The "prevalence" of the investigated MSK and "current" consultations for chronic pain increased with age, especially in women, but chronic pain remained stable at 22% for males aged > 40 years. The investigated MSK and chronic pain were more frequent among those in lower socioeconomic groups, veterans, Aboriginal and Torrent Strait Islanders, current and ex-smokers, and patients with chronic obstructive pulmonary disease or heart failure. CONCLUSIONS: The investigated MSK are more frequent among lower socioeconomic groups and the elderly. Based on information collected from adults attending Australian general practices, MedicineInsight provided similar estimates to those obtained from population-based studies, with the advantage of being based on medical diagnosis and including a national sample.
29491381 Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction 2018 Feb 28 Myeloid-derived suppressor cells (MDSCs) are heterogenous populations of immature myeloid progenitor cells with immunoregulatory function. MDSCs play critical roles in controlling the processes of autoimmunity but their roles in rheumatoid arthritis (RA) are controversial. The present study was undertaken to investigate whether MDSCs have therapeutic impact in mice with collagen-induced arthritis (CIA), an animal model of RA. We also examined the mechanisms underlying the anti-arthritic effect of MDSCs. In vitro treatment with MDSCs repressed IL-17 but increased FOXP3 in CD4+ T cells in mice. In vivo infusion of MDSCs markedly ameliorated inflammatory arthritis. Th17 cells and Th1 cells were decreased while Tregs were increased in the spleens of MDSCs-treated mice. MDSCs profoundly inhibited T cell proliferation. Addition of anti-IL-10 almost completely blocked the anti-proliferative effects of MDSCs on T cells. Anti-IL-10 blocked the expansion of Tregs by MDSCs. However, infusion of MDSCs from IL-10 KO mice failed to suppress inflammatory arthritis. MDSCs could reciprocally regulate Th17/Treg cells and suppress CIA via IL-10, suggesting that MDSCs might be a promising therapeutic strategy for T cell mediated autoimmune diseases including RA.
30244452 Histological Analysis of Arthritic Joints. 2018 Histological analysis is a morphological technique and an effective method for understanding the pathology of rheumatoid arthritis (RA). Here, we describe the processes of paraffin samples, including fixation, decalcifying, embedding, sectioning, and staining (hematoxylin and eosin, tartrate-resistant acid phosphatase, and immunohistochemistry) for an RA model mouse.
28097393 Comparative efficacy and safety of baricitinib 2 mg and 4 mg in patients with active r 2018 May OBJECTIVE: This study aimed to assess the relative efficacy and safety of once-daily baricitinib 2 mg and 4 mg administration in patients with active rheumatoid arthritis (RA). METHODS: In this network meta-analysis, randomized controlled trials (RCTs) examining the efficacy and safety of baricitinib in patients with active RA were included. A Bayesian network meta-analysis was conducted to combine the direct and indirect evidence from the RCTs. RESULTS: Seven RCTs involving 3461 patients met the inclusion criteria. There were ten pairwise comparisons, including seven direct comparisons and five interventions. The ACR20 response rate was significantly higher in the baricitinib 4 mg in combination with disease-modifying antirheumatic drugs (DMARD) group than in the placebo+DMARD group (odds ratio, OR 3.13; 95% credible interval, CrI 2.32-4.33). Compared with the placebo+DMARD group, the baricitinib 4 mg, baricitinib 2 mg + DMARD, and adalimumab 40 mg + methotrexate (MTX) groups showed a significantly higher ACR20 response rate. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4 mg + DMARD was likely to elicit the best ACR20 response rate (SUCRA = 0.7930), followed by baricitinib 4 mg (SUCRA = 0.7034), baricitinib 2 mg + DMARD (SUCRA = 0.6304), adalimumab 40 mg + MTX (SUCRA = 0.3687), and placebo+DMARD (SUCRA = 0.0045). By contrast, the safety based on the number of treatment-emergent adverse events (TEAEs) did not differ significantly among the five interventions. CONCLUSION: Baricitinib 2 mg and 4 mg administered once daily, in combination with DMARD, were efficacious interventions for active RA that had no significant risk of TEAE development.
30701888 Efficacy and tolerability of abatacept treatment: results of 12 months observation. 2018 May 11 AIM: This article reports 1-year clinical outcomes of patients with rheumatoid arthritis (RA) receiving abatacept (ABA) therapy. MATERIALS AND METHODS: Patients (n=91) with high RA activity (DAS28 = 5.1 ± 1.0) and an inadequate response on synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α inhibitors, 93%) were included in the study. The majority of patients were middle-aged (49 ± 13.5) womens, RF (72.5%) and ACPA (77%) positive, with moderate functional impairment - HAQ = 1.4 (0.9-2). ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR / ACR 2011 criteria using SDAI, CDAI, HAQ and the intention to treat approach. RESULTS: ABA led to a significant (p <0.05) decrease activity of RA. Clinical improvement according to EULAR criteria after 6 months of treatment was registered in 70.9%, after 12 months 63%. Almost a third of patients (28.7%) achieved a good response after 3 months of therapy, 39,2% - after 6 months and 39% - after 12 months. The retention rate of ABA therapy after 6 months was 77%, after 12 months - 60%. There were no significant differences between "bio-naive", 1 Bio and ≥2 Bio groups in achieving EULAR response. A good response was achieved in 38%, 38% and 43%, respectively, but the lowest number of non-responders was registered in ≥2 Bio - 38%, 36% and 43%. ABA significantly improved functional status of patients, after 12 months a marked and moderate improvement in the HAQ was achieved in 39% and 21% of patients, respectively. Adverse events (AE) were registered in 22 patients. The most frequent AE were upper respiratory tract infections - 11 (12%) patients. CONCLUSION: Abatacept was effective in the overall population, and in all subgroups of patients. It has shown significant improvement of clinical and functional status in patients who had an inadequate response to previous therapy. ABA has a good safety profile. AE were registered only in a small number of patients.
29609820 Dosimetry perspectives in radiation synovectomy. 2018 Mar Rheumatoid arthritis (RA) is a chronic inflammatory disease that can potentially damage the synovial joints. One of the effective treatment modality for RA is radiation synovectomy (RSV) where properly selected radionuclide is injected into the joint space, enabling controlled destruction of diseased synovial membrane via radiation exposure. Radiation dosimetry in RSV appears challenging due to the heterogeneous nature of synovial membrane, nonuniform distribution and leakage of radionuclide from the synovial cavity. This article reviews the dosimetric perspective pertaining to RSV. Specifically, characteristics of radionuclide for RSV and radiation dose to target and non-target (i.e., articular cartilage, bone, bloodstream, gonads, etc.) tissues of patient have been discussed. The personal dose H(p)(0.07) to the hands of medical staff (i.e., radiochemist, therapist physician, nurse) may be considerably high due to handling of high specific activities (∼500 MBq/ml for Y-90); such doses are typically measured using thermoluminescence dosimeters (TLD) ring dosimeters and ranges from 1 to 21.5, 0.1 to 40 and 0.1 to 5 µSv/MBq for the radiochemist, therapist physician and the nurse, respectively. Methods to minimize radiation doses to the patient, medical staff and public are elaborated. Contamination risks and precautionary measures are also reported.
30596705 Comparative study for haplotype block partitioning methods - Evidence from chromosome 6 of 2018 Haplotype-based methods compete with "one-SNP-at-a-time" approaches on being preferred for association studies. Chromosome 6 contains most of the known genetic biomarkers for rheumatoid arthritis (RA) disease. Therefore, chromosome 6 serves as a benchmark for the haplotype methods testing. The aim of this study is to test the North American Rheumatoid Arthritis Consortium (NARAC) dataset to find out if haplotype block methods or single-locus approaches alone can sufficiently provide the significant single nucleotide polymorphisms (SNPs) associated with RA. In addition, could we be satisfied with only one method of the haplotype block methods for partitioning chromosome 6 of the NARAC dataset? In the NARAC dataset, chromosome 6 comprises 35,574 SNPs for 2,062 individuals (868 cases, 1,194 controls). Individual SNP approach and three haplotype block methods were applied to the NARAC dataset to identify the RA biomarkers. We employed three haplotype partitioning methods which are confidence interval test (CIT), four gamete test (FGT), and solid spine of linkage disequilibrium (SSLD). P-values after stringent Bonferroni correction for multiple testing were measured to assess the strength of association between the genetic variants and RA susceptibility. Moreover, the block size (in base pairs (bp) and number of SNPs included), number of blocks, percentage of uncovered SNPs by the block method, percentage of significant blocks from the total number of blocks, number of significant haplotypes and SNPs were used to compare among the three haplotype block methods. Individual SNP, CIT, FGT, and SSLD methods detected 432, 1,086, 1,099, and 1,322 associated SNPs, respectively. Each method identified significant SNPs that were not detected by any other method (Individual SNP: 12, FGT: 37, CIT: 55, and SSLD: 189 SNPs). 916 SNPs were discovered by all the three haplotype block methods. 367 SNPs were discovered by the haplotype block methods and the individual SNP approach. The P-values of these 367 SNPs were lower than those of the SNPs uniquely detected by only one method. The 367 SNPs detected by all the methods represent promising candidates for RA susceptibility. They should be further investigated for the European population. A hybrid technique including the four methods should be applied to detect the significant SNPs associated with RA for chromosome 6 of the NARAC dataset. Moreover, SSLD method may be preferred for its favored benefits in case of selecting only one method.
29795407 Genome-wide association study of response to methotrexate in early rheumatoid arthritis pa 2018 Jul Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10(-7) for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
29554596 Quercetin attenuates zymosan-induced arthritis in mice. 2018 Jun Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNFα and IL-1β production, and gp91(phox), prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappa-B and induction of Nuclear factor erythroid 2- related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment.
30511206 An assessment of ocular elasticity using real time ultrasound and ocular response analyzer 2019 Oct PURPOSE: To investigate the elasticity of ocular structures in patients with rheumatoid arthritis (RA) without ocular involvement. METHODS: The study included 56 RA patients (study group) and 24 healthy volunteers as the control group. The rheumatoid arthritis patients were divided into two subgroups as those in active phase (Group 1, n = 25) or in remission phase (Group 2, n = 31) according to the disease activity index (DAS 28) score. The elastography values of the ratio of orbital fat-sclera (ROF/S) were measured with real-time US elastography, and corneal mechanical values were measured with the Reichert Ocular Response Analyzer in each eye. RESULTS: The mean ROF/S value was 5.2 ± 1.8 in Group 1, 0.7 ± 0.4 Group 2, and 0.6 ± 0.1 in the control group. There was a significant difference between the Group 1 and control group with regard to ROF/S (p < 0.001), but no significant difference was determined between Group 2 and control group (p > 0.05). The mean ROF/S value was a significant difference between the Group 1 and 2 (p < 0.001). ROF/S was significantly correlated with DAS-28 and C-reactive protein (CRP) (r = 0.816, p < 0.001 and r = 0.259, p = 0.006). CONCLUSIONS: ROF/S was significantly increased in patients in the active phase of RA. Findings revealed that ocular tissue structural changes may occur in the active phase and these could be related to ocular complications as a prognostic factor.
28836356 Model-Based Discovery and Development of Biopharmaceuticals: A Case Study of Mavrilimumab. 2018 Jan Drug development is a lengthy, costly process with low probability of success. Biopharmaceuticals are highly specific molecules, with efficacy and safety closely tied to target biology and pharmacology. The "learning-predicting-confirming" continuum by translational and clinical modeling and simulation (M&S) was implemented at every decision point for mavrilimumab, a human monoclonal antibody in development for rheumatoid arthritis (RA). This tutorial uses mavrilimumab as an example to demonstrate rational discovery, preclinical development, clinical study design, and dose selection of biotherapeutics by M&S.
29082659 Two-year persistence of golimumab as second-line biologic agent in rheumatoid arthritis as 2018 Feb OBJECTIVES: To evaluate the 2-year retention rate of golimumab compared with etanercept and adalimumab as second-line biologic agent in rheumatoid arthritis (RA) patients who failed a previous tumor necrosis factor inhibitor (TNFi). METHODS: Data on RA patients treated with a second-line subcutaneous TNFi were extracted from a multicentric Italian cohort (the LORHEN registry). The analysis was limited to etanercept, adalimumab and golimumab in the period when all were available in Italy (since October 2010). The 2-year retention rate was calculated by Kaplan-Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log-rank test. RESULTS: One hundred and ninety-five RA patients treated with etanercept (n = 76), adalimumab (n = 68) or golimumab (n = 51) were included in the analysis. The 2-year retention rate (40% with a median time-on-drug of 12.9 months in the whole population) was significantly lower for adalimumab (31.2%, P = 0.018) and numerically lower for etanercept (39.8%, P = 0.068) compared with golimumab (53.4%) because of a higher discontinuation rate due to adverse events (P = 0.042 and P = 0.038 versus golimumab, respectively). Drug survival was greater in concomitant synthetic disease modifying anti-rheumatic drug (sDMARD) users (44.2%) compared with TNFi monotherapy (22.5%, P = 0.036). No difference was found in survival analysis according to first-line TNFi reason for discontinuation and pattern of TNFi switch (antibody-receptor, antibody-antibody or receptor-antibody). CONCLUSIONS: Our real-life data confirmed switching to a second TNFi as a good option for treating first-line TNFi failures in RA, especially in combination with sDMARDs. Second-line golimumab showed an overall better 2-year drug survival compared with adalimumab and etanercept.
28880684 Reduction of methotrexate and glucocorticoids use after the introduction of biological dis 2018 May OBJECTIVES: To evaluate usage patterns for methotrexate (MTX) and/or glucocorticoids in rheumatoid arthritis (RA) patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) in daily practice. METHODS: Data from RA patients who commenced treatment with bDMARDs (infliximab [IFX], etanercept [ETN], tocilizumab [TCZ], or adalimumab [ADA]) from 2008 to 2010 were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The proportions of patients taking concomitant MTX and glucocorticoids and doses of these medications were evaluated before and 2 years after initiation of each bDMARD. RESULTS: A total of 470 RA patients who had initiated a bDMARD (IFX: n = 98, ETN: n = 181, TCZ: n = 90, and ADA: n = 101) were evaluated. The proportion of patients taking MTX decreased over time among ETN and TCZ users, while it increased among ADA users. The MTX dose decreased over time among IFX, ETN, and TCZ users, but not among ADA users. Although the rate of glucocorticoid use and dose decreased after bDMARD initiation in all four bDMARD groups, approximately 50% of patients continued to receive glucocorticoids 2 years after bDMARD initiation. CONCLUSION: MTX and glucocorticoid use and doses in daily practice were commonly reduced after the initiation of bDMARDs, with the dose adjustment varied depending on the bDMARD.
29661770 Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis. 2018 May 7 BACKGROUND AND OBJECTIVES: Hydroxychloroquine is widely used in patients with rheumatoid arthritis. However, large-scale studies examining the long-term effects of hydroxychloroquine on the development of kidney disease in patients with rheumatoid arthritis are lacking. We aimed to assess the long-term association of hydroxychloroquine use with the risk of developing CKD in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an observational cohort study for patients with newly diagnosed rheumatoid arthritis who were enrolled prospectively in Taiwan's National Health Insurance Research Database between January 1, 2000 and December 31, 2013. We used multivariable Cox proportional hazard regression to analyze the association of hydroxychloroquine use with incident CKD. RESULTS: A total of 2619 patients, including 1212 hydroxychloroquine users and 1407 hydroxychloroquine nonusers, were analyzed. Incident CKD was reported in 48 of 1212 hydroxychloroquine users and 121 of 1407 hydroxychloroquine nonusers. The incidence rate of CKD was lower in hydroxychloroquine users than in hydroxychloroquine nonusers (10.3 versus 13.8 per 1000 person-years). After multivariable adjustment, hydroxychloroquine users still had a lower risk of incident CKD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.90; P=0.01) than hydroxychloroquine nonusers. The lower risk of subsequent CKD development was dose dependent and consistent across subgroup analyses. CONCLUSIONS: Hydroxychloroquine use in patients with newly diagnosed rheumatoid arthritis is associated with a significantly lower risk of incident CKD compared with in nonusers.
29287749 Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix 2018 Jan PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers. METHODS: In this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics. FINDINGS: A total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t(1/2) was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab. IMPLICATIONS: Andecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.
27904997 Pleiotrophin, the angiogenic and mitogenic growth factor: levels in serum and synovial flu 2018 May BACKGROUND: Few studies have reported a possible involvement of pleiotrophin (PTN) in the pathophysiology of osteoarthritis (OA) and very little is known about its role in rheumatoid arthritis (RA). This study is to measure PTN in the sera and synovial fluids in RA and OA and to assess its relation to activity, functional class and radiological staging. SUBJECTS AND METHODS: Serum and synovial fluid samples were collected from 35 RA patients and 40 knee OA patients and serum samples were withdrawn from 20 healthy controls. Demographic, clinical and serological data were prospectively assessed. Functional and radiographic grades were also assessed. Serum and synovial fluid PTN levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no statistical significant differences (p > 0.05) on comparing the mean PTN level in sera of RA, OA patients and healthy controls. However the mean synovial fluid level of PTN in both patient groups was significantly higher than mean serum level (p < 0.001). Significant correlations between the serum PTN level and both morning stiffness duration (p = 0.008) and mHAQ score (p = 0.039) were only observed in RA patients. CONCLUSION: Our results point to a possible important role of PTN in RA and OA. We firstly report a serological pattern of PTN in the sera and synovial fluids of RA patients. However its implementation as a disease marker or a potential target therapy in both diseases awaits larger studies and further investigations.
30630793 A clinical study on the combined therapy of methotrexate and immuno adsorption in the trea 2018 Nov Objective of the present work was to study the effect and significance of the combined therapy of methotrexate and immune adsorption in the treatment of rheumatoid arthritis disease. 56 patients with rheumatoid arthritis disease who have received treatment in "The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China" during the period from May, 2016 to May, 2017 were selected as study objects and were randomized into control group and experimental group according to different therapies. Control group was given conventional therapy while experimental group was treated with the combined therapy of methotrexate and immune adsorption with 28 patients in each group. After a period of time, clinical symptoms, the experimental index, treatment effectiveness and the occurrence rate of adverse reactions were all compared between the two groups. Results revealed that the clinical symptoms and the experimental index of experimental group were less than those of control group and the occurrence rate of adverse reactions in experimental group was lower than that in control group. Additionally, the effective rate of experimental group was higher than that of control group and statistically significant difference was observed and revealed that the combined therapy of methotrexate and immune adsorption in the treatment of rheumatoid arthritis disease had vital significance in alleviating related symptoms, lowering adverse reactions occurrence rate and improving treatment effectiveness, being worthy of clinical application and promotion.
29720221 Deleterious role of hepatitis B virus infection in therapeutic response among patients wit 2018 May 2 BACKGROUND: Previous studies have revealed that hepatitis B virus (HBV) infection may be associated with rheumatoid arthritis (RA), while there are no further clinical studies regarding the role of HBV infection in RA progression during disease-modifying anti-rheumatic drug (DMARD) therapy. Here, we aimed to explore the influence of HBV infection on radiographic and clinical outcomes among patients with RA in a clinical practice setting. METHODS: Thirty-two consecutive patients with RA (Disease Activity Score 28-joint assessment based on C-reactive protein (DAS28-CRP) ≥2.6) with chronic HBV infection (CHB) were retrospectively recruited as the CHB group and 128 age-matched, sex-matched, and disease activity-matched contemporary patients with RA without CHB were included in the non-CHB group. Clinical data were collected at baseline and visits at month 1, 3, 6, and 12. The therapeutic target was defined as DAS28-CRP <2.6 in all patients or <3.2 in patients with long disease duration (>24 months). The primary outcome was the percentage of patients with one-year radiographic progression (a change in modified total Sharp score ≥0.5). RESULTS: Compared with the non-CHB group, a significantly higher percentage of patients with one-year radiographic progression was observed in the CHB group (53% vs. 17%, p < 0.001), with smaller proportions of patients achieving therapeutic target at month 6 and month 12 (53% vs. 82% and 53% vs. 75%, both p < 0.05), remission at month 6 (DAS28-CRP <2.6, 50% vs. 72%, p = 0.039), and American College of Rheumatology (ACR)20/50 responses and good or moderate European League Against Rheumatism (EULAR) responses mainly at month 6 and 12 (all p < 0.05). Multivariate logistic regression analysis revealed that CHB status was significantly associated with one-year radiographic progression and failure to achieve therapeutic target within 6 months. HBV reactivation occurred in 34% of patients with CHB during one-year follow up, with two patients suffering hepatitis flare. CONCLUSIONS: HBV infection may play a deleterious role in radiographic and clinical outcomes in patients with RA, and HBV reactivation should be paid close attention during immunosuppressive therapy.
28941147 Timing and Impact of Decisions to Adjust Disease-Modifying Antirheumatic Drug Therapy for 2018 Jun OBJECTIVE: Guidelines recommend that rheumatoid arthritis (RA) patients with moderate-to-high disease activity (MHDAS) adjust disease-modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner. METHODS: We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS. RESULTS: We identified 538 eligible subjects with 943.5 patient-years of followup. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 (interquartile range [IQR] 1-706) days and 301 (IQR 140-706) days, respectively. Being elderly (subdistribution hazard ratio [SHR] 0.61, P = 0.02), lower baseline disease activity (SHR 0.72, P < 0.01), longer duration of RA (SHR 0.98, P < 0.01), and biologic use (SHR 0.71, P < 0.01) were significantly associated with longer times to therapy adjustment. African American race (hazard ratio [HR] 0.63, P = 0.01), higher baseline disease activity (HR 0.75, P < 0.01), and not adjusting DMARD therapy within 90 days (HR 0.76, P = 0.01) were associated with longer times to LDAS. CONCLUSION: Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited >90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS.
29069507 Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities 2018 Jan 1 OBJECTIVES: Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate mechanisms of action and identify peripheral biomarkers associated with therapeutic responses of GM-CSF antagonism in RA. METHODS: A 24-week placebo (PBO)-controlled trial was conducted in 305 RA patients who received mavrilimumab (30, 100 or 150 mg) or PBO once every 2 weeks. Serum biomarkers and whole blood gene expression profiles were measured by protein immunoassay and whole genome microarray. RESULTS: Mavrilimumab treatment induced significant down-regulation of type IV collagen formation marker (P4NP 7S), macrophage-derived chemokine (CCL22), IL-2 receptor α and IL-6 compared with PBO. Both early and sustained reduction of P4NP 7S was associated with clinical response to 150 mg mavrilimumab treatment. Gene expression analyses demonstrated reduced expression of transcripts enriched in macrophage and IL-22/IL-17 signalling pathways after GM-CSF blockade therapy. Myeloid and T cell-associated transcripts were suppressed in mavrilimumab-treated ACR20 responders but not non-responders. While CCL22 and IL-6 down-regulation may reflect a direct effect of GM-CSFR blockade on the production of pro-inflammatory mediators by myeloid cells, the suppression of IL-2 receptor α and IL-17/IL-22 associated transcripts suggests an indirect suppressive effect of mavrilimumab on T cell activation. CONCLUSION: Our results demonstrated association of peripheral biomarker changes with therapeutic response to mavrilimumab in RA patients. The sustained efficacy of mavrilimumab in RA may result from both direct effects on myeloid cells and indirect effects on T cell activation after GM-CSFR blockade.