Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28794515 The complement system as a potential therapeutic target in rheumatic disease. 2017 Sep Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated.
29168210 Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung di 2018 Feb We report a case of a 30-year-old Chinese woman with rheumatoid arthritis and interstitial lung disease who abruptly developed generalized pustules and a high fever for 10 days. She had been taking oral prednisone, iguratimod and total glucosides of peony regularly for 5 months prior. In addition, she had taken metronidazole for 3 days 20 days prior which she had used before with no adverse reaction. She had no history of similar lesions and psoriasis. A biopsy of a pustule on the back showed spongiform pustule of Kogoj. She was suspected of having generalized pustular psoriasis or acute generalized exanthematous pustulosis. Finally, she was diagnosed with generalized pustular psoriasis (von Zumbusch type) considering the characteristics and clinical course of the rash. In addition to the above three drugs, systemic cyclosporin (5 mg/kg per day) was applied, and the lesions and fever resolved within the proceeding 2 months.
28374332 Prevalence and risk factors associated with glucocorticoid-induced osteoporosis in Chinese 2017 Dec Usage of glucocorticoid (GC) is a strong risk factor of osteoporosis (OP) and osteoporotic fracture (OPF) in Chinese patients with rheumatoid arthritis (RA). Controlling GC daily dosage and shortening GC course are helpful in preventing glucocorticoid-induced osteoporosis (GIOP) and OPF for Chinese patients with RA. INTRODUCTION: This study aims to investigate the prevalence and risk factors of GIOP, and also identify influences of GC daily dosage and GC treatment course for GIOP in Chinese patients with RA. METHODS: Seven hundred and ninety patients with RA and 158 normal subjects were enrolled in the study. Clinical and laboratory features and medications of GC were recorded in detail. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in all subjects. RESULTS: BMD at all measured sites in RA was significantly lower than that in control group. Prevalence of OP was obviously higher in RA with GC group (41.6%), compared with RA without GC group (29.4%). Prevalence of OPF in group of RA with GC (21.0%) was higher than that in group of RA without GC (13.3%). Usage of GC, female, and age were risk factors for the occurrence of OP and OPF in RA, while body mass index (BMI) was the protective factor of OP. Prevalence of GIOP and OPF had statistical significance among groups of different treatment courses with GC, whereas no statistical difference was found among groups with different daily dosages of GC. CONCLUSIONS: GIOP exists generally in Chinese patients with RA, which relates to treatment course not daily dosage of GC. Usage of GC is also the risk factor for the happening of OPF in Chinese patients with RA.
28324194 Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus a 2017 Jun The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.
29070531 Affinity maturation shapes the function of agonistic antibodies to peptidylarginine deimin 2018 Jan OBJECTIVES: The citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is the target of a polyclonal group of autoantibodies in patients with rheumatoid arthritis (RA). A subgroup of such antibodies, initially identified by cross-reactivity with peptidylarginine deiminase type 3 (PAD3), is strongly associated with progression of radiographic joint damage and interstitial lung disease and has the unique ability to activate PAD4. The features of these antibodies in terms of their T cell-dependent origin, genetic characteristics and effect of individual antibody specificities on PAD4 function remain to be defined. METHODS: We used PAD4 tagged with the monomeric fluorescent protein mWasabi to isolate PAD4-specific memory B cells from anti-PAD4 positive patients with RA and applied single cell cloning technologies to obtain monoclonal antibodies. RESULTS: Among 44 single B cells, we cloned five antibodies with PAD4-activating properties. Sequence analysis, germline reversion experiments and antigen specificity assays suggested that autoantibodies to PAD4 are not polyreactive and arise from PAD4-reactive precursors. Somatic mutations increase the agonistic activity of these antibodies at low calcium concentrations by facilitating their interaction with structural epitopes that modulate calcium-binding site 5 in PAD4. CONCLUSIONS: PAD4-activating antibodies directly amplify a key process in disease pathogenesis, making them unique among other autoantibodies in RA. Understanding the molecular basis for their functionality may inform the design of future PAD4 inhibitors.
28535891 Impact of rheumatoid arthritis in the public health system in Santa Catarina, Brazil: a de 2017 May INTRODUCTION: There are few studies that carried out a descriptive and trend analysis based on available data from the Unified Health System (SUS) between pre- and post-free dispensing of pharmacological treatment of rheumatoid arthritis (RA) from the perspective of the public health system, in terms of the direct cost of the disease among adults and elderly residents of the State of Santa Catarina, Brazil. This study aims to characterize the direct cost of medical and surgical procedures before and after the dispensing of drugs in this state. METHODS: This is a time series-type study with a cross-sectional survey of data from the Hospital (SIH) and Outpatient (SIA) Information System of SUS during the period from 1996 to 2009. RESULTS: Between 1996 and 2009, the total expenditure for hospital- and outpatient pharmacological treatment of rheumatoid arthritis was R$ 26,659,127.20. After the dispensing of drug treatment by SUS a decrease of 36% in the number of hospital admissions was observed; however, an increase of 19% in clinical procedures was noted. CONCLUSION: During the observed period, a reduction in the number of hospital admissions for both clinical and orthopedic surgical procedures related to this disease was observed. Nevertheless, there was an increase in the cost of medical admissions.
28439057 [Calcium and bone metabolism across women's life stages. Osteoporosis in female patients w 2017 Female patients with rheumatoid arthritis(RA)are at high risk for osteoporosis and fractures. In Japanese female patients with RA, age, disability, daily prednisolone dose, history of total knee replacement, and low bone mineral density are known to be risk factors for fractures, and more than 70% are reported to be vitamin D deficiency.
29071482 [Nontuberculous mycobacterial infections]. 2017 Nov Nontuberculous mycobacterial (NTM) are found ubiquitously in the environment and are usually of low pathogenicity. Infection occurs via inhalation of aerosols, and some species may cause severe infections. The incidence of NTM infections is rising worldwide. The risk of developing NTM disease depends on the susceptibility of the host as well as the frequency and duration of exposure. In addition to congenital immune deficiencies and immunosuppressive therapy, structural lung and systemic diseases, including rheumatoid arthritis (RA), are associated with an increased risk for NTM infections. The immune response to NTM is complex and relies on the interplay between professional phagocytes and lymphoid cells. This interplay is concerted by three key cytokines: interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Targeted immunotherapies, e. g., treatment with TNF inhibitors, interfere with these essential pathways and increase the risk of NTM infection significantly. This review focuses on the relationship between the immune response to NTM and intrinsic and iatrogenic dispositions for NTM infection, with an emphasis on RA.
27269649 The changing face of septic arthritis complicating rheumatoid arthritis in the era of biot 2017 Jan OBJECTIVES: To see whether the frequency and features of septic arthritis (SA) complicating rheumatoid arthritis (RA) have changed over the last 35years. METHODS: This retrospective single-center study included all patients hospitalized at the rheumatology department for SA bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979-2002 (before biotherapies) and 2003-2013 (the era of biotherapies) were compared. RESULTS: Between 1979 and 2013, 64/514 (12.5%) SA presented with a RA - 21/157 (13.4%) in the 2003-2013 period and 43/357 (12.0%) in the 1979-2002 period. Over the past decade, median age of RA SA patients increased (61 vs. 68 years; P<0.02) and predominant gender became males (52% vs. 40%). The features of the RA remained unchanged: history (18 vs. 16years), rheumatoid factor (95% vs. 87%), and corticosteroids (91% vs. 81%). Over the last decade 24% (vs. 0; P<0.003) of the patients received a biologic DMARD: etanercept (n=2), adalimumab (n=1), rituximab (n=1), tocilizumab (n=1). Proportion of polyarticular infection had decreased strongly (9.5% vs. 37%; P<0.02). Proportion of Staphyloccus aureus infections remained stable, but there was a higher incidence of MRSA infections (31 vs. 6%; P<0.05). Blood cultures less often tested positive (29% vs. 47%; NS). Case fatality rate had fallen slightly in RA SA (5% vs. 9%; NS), but not in non-RA SA cases (7% vs. 6%; NS). CONCLUSION: This study brings reassuring findings - in the era of biotherapies, the rate of septic arthritis amongst patients with RA has not increased, and the most severe septic polyarticular forms are on the decline.
27856937 Allylpyrocatechol Attenuates Collagen-Induced Arthritis via Attenuation of Oxidative Stres 2017 Feb Rheumatoid arthritis (RA), an inflammatory autoimmune disorder, is characterized by synovial hyperplasia and bony destruction. The pathogenesis of RA includes redox dysregulation, concomitant with increased levels of proinflammatory mediators. As the ability of allylpyrocatechol (APC), a phytoconstituent of Piper betle leaves, to alleviate oxidative stress has been demonstrated in patients with RA, its antiarthritic activity was evaluated in an animal model of arthritis, and the underlying mechanism(s) of action clarified. The animal model was established by immunizing rats with bovine collagen type II (CII) followed by lipopolysaccharide, along with a booster dose of CII on day 15. Rats were treated with APC or methotrexate (MTX) from days 11 to 27, when paw edema, radiography, histopathology, and markers of inflammation were evaluated. The pro/antiinflammatory signaling pathways were studied in a RAW264.7 macrophage cell line. Allylpyrocatechol (APC) prevented the progression of arthritis as was evident from the reduction in paw edema, and attenuation of damage to bones and cartilage shown by radiography and histopathology. Additionally, there was reduction in the levels of proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] and restoration of the redox balance. Importantly, MTX ameliorated the features of arthritis but not the associated oxidative stress. In RAW264.7, APC inhibited generation of nitric oxide and proinflammatory cytokines (TNF-α, IL-6, and IL-12p40), and modulated the phosphorylation of proinflammatory (extracellular signal-regulated kinase 1/2, stress-activated protein kinase/c-Jun N-terminal protein kinase, and Janus kinase/signal transducers and activators of transcription) and cytoprotective (nuclear factor erythroid 2-related factor 2, heme oxygenase-1) signaling pathways. Taken together, APC controlled the development of arthritis, possibly via modulation of signaling pathways, and deserves further consideration as a therapy for RA.
28167861 Self-Reported Childhood Maltreatment and Traumatic Events among Israeli Patients Suffering 2017 Objective. The association between Fibromyalgia Syndrome (FMS) and childhood maltreatment and adversity has frequently been proposed but limited data exists regarding the transcultural nature of this association. Methods. 75 Israeli FMS patients and 23 Rheumatoid Arthritis (RA) patients were compared. Childhood maltreatment was assessed by the Childhood Trauma Questionnaire (CTQ) and potential depressive and anxiety disorders were assessed by the Patient Health Questionnaire-4. FMS severity was assessed by the Widespread Pain Index (WPI), the Symptom Severity Score (SSS), and the FIQ. PTSD was diagnosed according to the DSM IV. RA severity was assessed by the RA Disease Activity Index. Health status was assessed by the SF-36. Results. Similar to reports in other countries, high levels of self-reported childhood adversity were reported by Israeli FMS patients. PTSD was significantly more common among FMS patients compared with RA patients, as well as childhood emotional abuse and physical and emotional neglect. Levels of depression and anxiety were significantly higher among FMS patients. Conclusion. The study demonstrated the cross cultural association between FMS and childhood maltreatment, including neglect, emotional abuse, and PTSD. Significant differences were demonstrated between FMS patients and patients suffering from RA, a model of an inflammatory chronic rheumatic disease.
28161110 [Discontinuation or tapering strategies of biologics in rheumatoid arthritis in remission] 2017 Apr The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable.
28944919 Proprotein convertase subtilisin/kexin type 6 promotes in vitro proliferation, migration 2017 Dec Our previous studies demonstrated that expression of proprotein convertase subtilisin/kexin type 6 (PCSK6) is greatly enhanced in rheumatoid arthritis fibroblast‑like synoviocytes (RASFs), and that PCSK6 inhibition decreases cell proliferation, migration and invasion. The present study aimed to investigate the functional role of PCSK6 in the hyperplasia of RASFs. Cultured RASFs from RA patients were stimulated with recombinant human (rh)PCSK6. Subsequent changes in proliferation, invasion, migration and the secretion of inflammatory cytokines were measured in vitro using MTT, wound healing and Transwell assays, and ELISA. Cell cycle and apoptosis were analyzed by flow cytometry. Influence on downstream gene expression levels were analyzed using reverse transcription‑quantitative polymerase chain reaction. Specific signaling pathways responsible for these effects were analyzed using western blotting and confirmed with pathway‑specific inhibitors. It was demonstrated that rhPCSK6 significantly increased RASF cell invasion, migration and proliferation, which was influenced through both reduced cell cycle arrest and reduced apoptosis. Furthermore, rhPCSK6 stimulated RASFs to secrete the inflammatory cytokines interleukin (IL)‑1α, IL‑1β and IL‑6, and exhibit altered expression of genes involved in angiogenesis, hypoxia, proliferation and inflammation. These cellular effects were mediated via the nuclear factor (NF)‑κB, signal transducer and activator of transcription 3 (STAT3) and extracellular signal regulated (ERK)1/2 signaling pathways. The results demonstrated that signaling via NF‑κB and STAT3 mediated cell cycle arrest, and signaling through NF‑κB mediated apoptosis in RASF cells stimulated with PCSK6. PCSK6 can activate NF‑κB, STAT3 and ERK1/2 signaling pathways in vitro to enhance cell proliferation, migration, invasion and inflammation in RASF cells. These findings suggest that PCSK6 may be an important therapeutic target in RA.
28882568 Identification of pathogenic genes related to rheumatoid arthritis through integrated anal 2017 Nov 15 The purpose of our study was to identify new pathogenic genes used for exploring the pathogenesis of rheumatoid arthritis (RA). To screen pathogenic genes of RA, an integrated analysis was performed by using the microarray datasets in RA derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Afterwards, the integrated analysis of DNA methylation and gene expression profiling was used to screen crucial genes. In addition, we used RT-PCR and MSP to verify the expression levels and methylation status of these crucial genes in 20 synovial biopsy samples obtained from 10 RA model mice and 10 normal mice. BCL11B, CCDC88C, FCRLA and APOL6 were both up-regulated and hypomethylated in RA according to integrated analysis, RT-PCR and MSP verification. Four crucial genes (BCL11B, CCDC88C, FCRLA and APOL6) identified and analyzed in this study might be closely connected with the pathogenesis of RA.
28741989 Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression i 2018 May OBJECTIVES: Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs). METHODS: Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography. RESULTS: GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression. CONCLUSIONS: Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.
27995382 Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. 2017 Mar The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10° increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 ± 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p < 0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p < 0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p < 0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.
28320050 Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross-National 2018 Jan OBJECTIVE: The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease-modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan. METHODS: We conducted a retrospective cohort study, including RA patients starting a first DMARD in the US or Taiwan. The first date patients newly received any DMARD was defined as the index date, and the 1-year period before the index date was the baseline period. HBV testing was defined as any of the following tests 1 year before or after the index date: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, or HBV DNA. We calculated the HBV testing rate by year and used Poisson regression to calculate the testing rate ratio. RESULTS: We identified 14,568 RA patients in the US and 46,265 in Taiwan. The overall testing rate was 20.3% in the US and 24.5% in Taiwan, and gradually increased over the study period from 13.1-23.0% in the US and 16.8-30.0% in Taiwan. More than one type of HBV test was used in 43.4% of patients in the US and 16.3% of patients in Taiwan receiving tests. Results of Poisson regression found Taiwan had a 17% higher testing rate over the US during the followup period (crude rate ratio 1.17 [95% confidence interval 1.12-1.22]). CONCLUSION: We found small differences in the HBV testing rates across the US and Taiwan. Although the rate gradually increased in the past decade, it remained low in both countries.
28618762 Antiinflammatory and antioxidant effects of gemcitabine in collagen-induced arthritis mode 2017 Jun 12 BACKGROUND/AIM: Gemcitabine (GEM) has antiproliferative effects on lymphocytes, which are potent pathogenic actors of rheumatoid arthritis (RA). The aim of the study was to investigate the therapeutic potential of GEM on collagen-induced arthritis (CIA). MATERIALS AND METHODS: Arthritis was induced by the intradermal injection of chicken type II collagen with incomplete Freund's adjuvant into albino Wistar rats. Doses of 5 and 20 mg/kg GEM were administered twice a week after the 14th day, which marked the onset the arthritis. Serum IL-17, TNF-α, malondialdehyde, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels and tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels were analyzed. RESULTS: Histopathologically prevalent inflammation and cartilage/bone destruction were observed in the arthritis group. Moreover, in the arthritis group serum IL-17, TNF-α, and malondialdehyde levels were significantly increased while catalase, SOD, GPx, HO-1, and Nrf2 levels were significantly decreased. However, in the GEM-treated groups, decreased TNF-α, IL-17, and malondialdehyde levels; increased SOD, catalase, GPx, Nrf2, and HO-1 levels; and ameliorated perisynovial inflammation and cartilage/bone destruction were observed. CONCLUSION: GEM suppresses cytokine levels and enhances antioxidant activity. It also prevents cartilage/bone destruction in the CIA model. GEM may be a viable candidate for research into the treatment of RA.
28529116 Italian consensus Guidelines for the management of hepatitis B virus infections in patient 2017 Oct OBJECTIVES: Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations. METHODS: The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. RESULTS: A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed. CONCLUSIONS: HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment.
28159704 Effects of targeted therapies on the bone in arthritides. 2017 Mar Inflammatory arthritides, such as rheumatoid arthritis (RA) and spondyloarthritides (SpA) have been associated with both localized bone resorption and/or formation, and generalized osteoporosis. Systemic inflammation may be the major driver for bone loss in arthritis. In RA and peripheral SpA the RANK-RANKL-OPG network is involved in bone resorption, while in axial SpA the Wnt-β-catenin axis and its inhibitors (DKK-1, sclerostin) are the most relevant. Targeted therapies including biologics and small molecule tyrosine kinase inhibitors may interfere with inflammatory bone metabolism. Most of these compounds are able to slow down radiographic progression and osteoporosis in arthritides. In very early cases of non-radiological SpA, there may be a window of opportunity allowing to prevent syndesmophyte formation. The inability of targeted therapies to increase the production of DKK-1 and sclerostin may explain the lack of efficacy of TNF inhibitors to halt syndesmophyte formation in SpA. Further clinical trials are needed to better understand the bone effects of targeted therapies.