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ID PMID Title PublicationDate abstract
29434586 Bioactive Lipids and Chronic Inflammation: Managing the Fire Within. 2018 Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes. They are secreted by basically all cells involved in inflammatory processes and constitute the crucial infrastructure that triggers, coordinates and confines inflammatory mechanisms. However, these molecules are also deeply involved in the detrimental transition from acute to chronic inflammation, be it for persistent or excessive action of pro-inflammatory lipids or for the impairment of the functions carried out by resolving ones. As a matter of fact, bioactive lipids have been linked, to date, to several chronic diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis. This review summarizes current knowledge on the involvement of the main classes of endogenous bioactive lipids-namely classical eicosanoids, pro-resolving lipid mediators, lysoglycerophospholipids/sphingolipids, and endocannabinoids-in the cellular and molecular mechanisms that lead to the pathogenesis of chronic disorders.
30323820 Bone Remodeling and the Role of TRAF3 in Osteoclastic Bone Resorption. 2018 Skeletal health is maintained by bone remodeling, a process in which microscopic sites of effete or damaged bone are degraded on bone surfaces by osteoclasts and subsequently replaced by new bone, which is laid down by osteoblasts. This normal process can be disturbed in a variety of pathologic processes, including localized or generalized inflammation, metabolic and endocrine disorders, primary and metastatic cancers, and during aging as a result of low-grade chronic inflammation. Osteoclast formation and activity are promoted by factors, including cytokines, hormones, growth factors, and free radicals, and require expression of macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) by accessory cells in the bone marrow, including osteoblastic and immune cells. Expression of TNF receptor-associated factor 6 (TRAF6) is required in osteoclast precursors to mediate RANKL-induced activation of NF-κB, which is also necessary for osteoclast formation and activity. TRAF3, in contrast is not required for osteoclast formation, but it limits RANKL-induced osteoclast formation by promoting proteasomal degradation of NF-κB-inducing kinase in a complex with TRAF2 and cellular inhibitor of apoptosis proteins (cIAP). TRAF3 also limits osteoclast formation induced by TNF, which mediates inflammation and joint destruction in inflammatory diseases, including rheumatoid arthritis. Chloroquine and hydroxychloroquine, anti-inflammatory drugs used to treat rheumatoid arthritis, prevent TRAF3 degradation in osteoclast precursors and inhibit osteoclast formation in vitro. Chloroquine also inhibits bone destruction induced by ovariectomy and parathyroid hormone in mice in vivo. Mice genetically engineered to have TRAF3 deleted in osteoclast precursors and macrophages develop early onset osteoporosis, inflammation in multiple tissues, infections, and tumors, indicating that TRAF3 suppresses inflammation and tumors in myeloid cells. Mice with TRAF3 conditionally deleted in mesenchymal cells also develop early onset osteoporosis due to a combination of increased osteoclast formation and reduced osteoblast formation. TRAF3 protein levels decrease in bone and bone marrow during aging in mice and humans. Development of drugs to prevent TRAF3 degradation in immune and bone cells could be a novel therapeutic approach to prevent or reduce bone loss and the incidence of several common diseases associated with aging.
30285854 Racial differences in comorbidity profile among patients with chronic obstructive pulmonar 2018 Oct 4 BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by multiple comorbidities, which are associated with an increased risk of exacerbation, a poor health-related quality of life, and high mortality. However, differences in comorbidity profile by race and ethnicity in COPD patients have not been fully elucidated. METHODS: Participants aged 40 to 79 years with spirometry-defined COPD from the U.S. National Health and Nutrition Examination Survey (NHANES) (2007-2012) and from the Korea NHANES (2007-2015) were analyzed to compare the prevalence of comorbidities by race and ethnicity group. Comorbidities were defined using questionnaire data, physical exams, and laboratory tests. RESULTS: Non-Hispanic Whites had the highest prevalence of dyslipidemia (65.5%), myocardial infarction (6.2%), osteoarthritis (40.1%), and osteoporosis (13.6%), while non-Hispanic Blacks had the highest prevalence of asthma (24.0%), hypertension (70.2%), stroke (7.3%), diabetes mellitus (DM) (23.3%), anemia (16.4%), and rheumatoid arthritis (11.9%). Compared to non-Hispanic Whites, non-Hispanic Blacks had a significantly higher prevalence of hypertension, stroke, DM, anemia, and rheumatoid arthritis after adjusting for age, sex, body mass index, and smoking status, while Hispanics had a significantly higher prevalence of DM and anemia, and Koreans had significantly lower prevalences of all comorbidities except stroke, DM, and anemia. CONCLUSIONS: COPD-related comorbidities varied significantly by race and ethnicity, and different strategies may be required for the optimal management of COPD and its comorbidities in different race and ethnicity groups.
29496270 [Scleritis and systemic diseases: What should know the internist?]. 2018 Sep Scleritis is an inflammatory disease of the sclera; outer tunic of the eye on which the oculomotor muscles are inserted. It can be associated with a systemic disease up to one time out of 3. These associated diseases are mainly rheumatoid arthritis, vasculitis, including granulomatosis with polyangiitis in the first line and spondyloarthropathies. Before mentioning such an etiology, it is necessary to eliminate an infectious cause, mainly herpetic, which is regularly underestimated. The classification of scleritis is clinical. We distinguish between anterior scleritis and posterior scleritis. Anterior scleritis is diffuse or nodular, usually of good prognosis. Anterior necrotizing scleritis with inflammation is often associated with an autoimmune disease, necrotizing scleritis without inflammation usually reflects advanced rheumatoid arthritis. The treatment of these conditions requires close collaboration between internists and ophthalmologists to decide on the use of corticosteroid therapy with or without immunosuppressors or biotherapies.
30687070 Successful Certolizumab Pegol Treatment of Chronic Anterior Uveitis Associated with Psoria 2018 Sep This report presents details on a 45-year-old male Japanese patient with chronic and refractory anterior uveitis associated with psoriasis vulgaris who was administered certolizumab pegol (CZP), which is an anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody. Although CZP has only been formally approved for rheumatoid arthritis treatment in Japan, a clinical trial allowed us to assess CZP effectiveness in this patient. The grade 3+ anterior chamber inflammation (for both the cells and flare) observed at baseline improved to grade 0 at 3 months post-treatment. Dermatologically, the psoriasis area severity index (PASI) score was 25.4, while the body surface area (BSA) was 88% at baseline. At 3 months after treatment, the scores improved to 2.8 for PASI and less than 1% for BSA. After the treatment, remission has lasted for at least 9 months. No adverse events were seen during the CZP treatment. These findings suggest that CZP could be an effective therapeutic alternative in some refractory anterior uveitis patients with psoriasis vulgaris.
29503444 Genetic and epigenetic influences on the loss of tolerance in autoimmunity. 2018 Jun Immunological tolerance loss is fundamental to the development of autoimmunity; however, the underlying mechanisms remain elusive. Immune tolerance consists of central and peripheral tolerance. Central tolerance, which occurs in the thymus for T cells and bone marrow for B cells, is the primary way that the immune system discriminates self from non-self. Peripheral tolerance, which occurs in tissues and lymph nodes after lymphocyte maturation, controls self-reactive immune cells and prevents over-reactive immune responses to various environment factors. Loss of tolerance results in autoimmune disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and primary biliary cirrhosis (PBC). The etiology and pathogenesis of autoimmune diseases are highly complicated. Both genetic predisposition and epigenetic modifications are implicated in the loss of tolerance and autoimmunity. In this review, we will discuss the genetic and epigenetic influences on tolerance breakdown in autoimmunity. Genetic and epigenetic influences on autoimmune diseases, such as SLE, RA, T1D and PBC, will also be briefly discussed.
29197623 Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidog 2018 Mar 1 There are reports of sulfasalazine (Salazosulfapyridine; SASP)-induced reproductive toxicity, but there it is not known whether the SASP molecule or its intestinal metabolites are responsible for this effect. Rats received SASP (150, 300, and 600mg/kg) for 60 consecutive days (in vivo). Additionally, epididymal sperm was isolated and incubated with SASP (10μM-1600μM) (in vitro). Markers of oxidative stress, mitochondrial function, and sperm functionality, along with testis histopathology as well as several steroidogenic genes and proteins, including steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage enzyme (P450scc; Cyp11a), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) were measured. SASP toxicity was evident as shown by severe testicular histopathological alterations, along with poor sperm parameters and increased markers of oxidative stress. Plasma testosterone level and steroidogenesis-related gene and protein (StAR, 3-beta-HSD, 17-beta-HSD) expressions, as well as mitochondrial membrane potential, were significantly decreased at high doses of SASP (in vivo). Interestingly, in vitro treatment of sperm with SASP not only caused no significant detrimental effect on rat sperm but also increased parameters of sperm functionality and decreased markers of oxidative stress. SASP had paradoxical actions on the rat sperm in these experimental models. The findings might be useful in understanding the mechanism(s) of SASP-induced reproductive toxicity. The present findings have opened a new molecular window into the relationship between disrupted steroidogenesis and mammalian reproduction indices and also are vital regarding clinical administration of SASP and human reproductive health.
30419221 Exosomes in inflammation and role as biomarkers. 2019 Jan Exosomes are endosomal-derived nano-vesicles. They are considered vehicles through which donor cells transfer proteins, lipids and nucleic acids to target cells thus influencing their metabolism. Exosomes are involved in inflammatory processes that play a pivotal role in a large number of pathologic states including cancer, inflammatory bowel diseases, type 2 diabetes, obesity, rheumatoid arthritis and neurodegenerative diseases. The association between inflammation and change in nature or expression level of some exosomal cargos is the fundamental step for identifying possible novel biomarkers of inflammatory-based diseases. A novel interesting exosome cargo is the SLC22A5 transport protein whose level in exosomes is regulated by the pro-inflammatory cytokine INF-γ. The advantage of using exosomes as a biomarker vehicle consists of their ease of collection from body fluids such as urine and saliva as they may represent a non-invasive means for screening human pathology.
29930806 Synovial fluid uric acid level aids diagnosis of gout. 2018 Jul Examination of urate crystal in synovial fluid (SF) remains the gold standard for diagnosis of gout, but is not universally available. SF uric acid (UA) level may be measured by the uricase method with an automated analyzer. The present study aimed to evaluate the utility of SF to serum UA ratio (SSR) for diagnosis of gout. A cross-sectional study was conducted at the National Center for Rheumatic Diseases, Nepal. Patients presenting with acute (<1 day) joint pain and/or swelling were included. Aspiration was performed in all patients and fluid was subjected to testing for urate level, pH and cell counts and microscopy. Serum samples were also assessed for urate levels, and the SSR was calculated for each patient. A receiver operating characteristic curve was plotted to determine the cutoff value for indicating diagnosis of gout. The difference in SSR between gout and non-gout effusion was evaluated by one-way analysis of variance. A total of 181 patients were included of which 77 had gout. The remaining cases included osteoarthritis, pseudogout, rheumatoid arthritis and ankylosing spondylitis. SSR was significantly higher in gout patients than in any other group (P<0.05). An SSR of ≥1.01 had the highest sensitivity and specificity at 89.6 and 66.3%, respectively, for identifying gout effusion. The present results indicated that SSR may be used as an aid for gout diagnosis when polarizing microscopy is not available.
29888028 New technique for C1-C2 fixation. 2018 BACKGROUND: There are several techniques for treating atlantoaxial instability, including the Magerl transarticular screw fixation and the Harms/Goel C1-C2 screw rod techniques. Here, we present a novel technique utilizing a polyaxial screw rod system and a combination of C1 lateral mass and C1-C2 transarticular screws. METHODS: We retrospectively reviewed 14 patients (7 women, 7 men; mean age 62) who underwent surgery for type II odontoid fractures (n = 7), pseudarthrosis after anterior odontoid screw placement (n = 3), Os odontoideum (n = 2), atlantoaxial instability after C3-C5 fusion (n = 1), and craniovertebral rheumatoid arthritis (n = 1). Ten patients underwent posterior C1-C2 fixation, three patients with osteoporosis had C1-C4 fixation, and one patient had C1-Th1 fixation. The mean follow-up time was 22 months. RESULTS: Intraoperatively, there were no complications (e.g., vertebral artery, nerve root, or spinal cord injury). Postoperative imaging showed no screw malpositioning, and no screw loosening, fracture, or bone absorption around the screws. Furthermore, all patients exhibited postoperative improvement in neck pain. CONCLUSIONS: C1 lateral mass and C1-C2 transarticular polyaxial screw rod fixation techniques were effective in achieving immediate rigid immobilization of the C1-C2 motion segment.
29847817 Bamboo Nodes of Vocal Folds: A Description of 10 Cases and Review of the Literature. 2018 OBJECTIVE: Bamboo nodes are vocal fold lesions, mostly associated with autoimmune diseases. PATIENTS AND METHODS: This is a retrospective clinical study including 10 patients with bamboo nodes. Data were collected regarding associated autoimmune disorder and type of treatment. A systematic review of the literature was conducted. RESULTS: All patients were women, with hoarseness as the most frequent symptom. There was in most cases an associated autoimmune disease: 3 patients with systemic lupus erythematosus; 3 with rheumatoid arthritis; 1 with Sjögren syndrome; 1 with Hashimoto disease; and 1 with mixed connective tissue disease. Four patients were treated with speech therapy, 3 with oral steroids, 1 with speech therapy and oral steroids combined, 1 with oral steroids and laryngeal steroid injections, and 1 had oral steroids, surgery, and speech therapy. Speech therapy was the first-line treatment. CONCLUSION: Bamboo nodes should be looked for in every patient with a diagnosis of autoimmune disease complaining of dysphonia.
29451523 [Towards new therapeutic paradigms beyond symptom control in the management of inflammator 2018 Jan Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic relapsing conditions that may result in progressive bowel damage, high risk of complications, surgery and permanent disability. The conventional therapeutic approach for inflammatory bowel diseases is based mainly on symptom control. Unfortunately, a symptom-based therapeutic approach has little impact on major long-term disease outcomes. In other chronic disabling conditions such as diabetes, hypertension and rheumatoid arthritis, the development of new therapeutic approaches has led to better outcomes. In this context a "treat to target" strategy has been developed. This strategy is based on identification of high-risk patients, regular assessment of disease activity by means of objective measures, adjustment of treatment to reach the pre-defined target. A treat to target approach has recently been proposed for inflammatory bowel disease with the aim at modifying the natural history of the disease. In this review, the evidence and the limitations of the treat to target paradigm in inflammatory bowel disease are analyzed and discussed.
29439901 Development of a fluorescent probe for detection of citrulline based on photo-induced elec 2018 Mar 1 Peptidyl arginine deiminases (PADs) catalyze the post-translational deimination of peptidyl arginine residues to form citrulline residues. Aberrant citrullination of histones by one of the PAD isozymes, PAD4, is associated with various diseases, including rheumatoid arthritis, so high-throughput screening systems are needed to identify PAD4 inhibitors as chemical tools to investigate the role of PAD4, and as candidate therapeutic agents. Here, we utilized the addition-cyclization reaction between phenylglyoxal and citrulline under acidic conditions to design turn-on fluorescent probes for citrulline based on the donor-excited photoinduced electron transfer (d-PeT) mechanism. Among several derivatives of phenylglyoxal bearing a fluorescent moiety, we found that FGME enabled detection of citrulline without a neutralization process, and we used it to establish a simple methodology for turn-on fluorescence detection of citrulline.
28988197 Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansopraz 2018 Jun OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results.
30370485 Autoimmune disease-associated non-Hodgkin's lymphoma-a large retrospective study from Chin 2019 Feb The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n = 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P = 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis.
30168281 Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical 2019 Feb AIM: Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting. METHODS: The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated. RESULTS: One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively. CONCLUSION: Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.
29694270 Higher Incidence Rates of Comorbidities in Patients with Psoriatic Arthritis Compared with 2019 Jan BACKGROUND: Psoriatic arthritis (PsA) is associated with multiple comorbid conditions, including cardiovascular (CV) comorbidities that impose a considerable burden on patients. Effective management of PsA requires an understanding of comorbidity profiles. OBJECTIVE: To compare the frequency and incidence rates of comorbidities and hospitalizations among newly diagnosed PsA patients and a matched general population without PsA, using large national claims databases in the United States. METHODS: This retrospective observational study used MarketScan databases from January 1, 2008, to September 30, 2015, to identify adult patients with newly diagnosed PsA (i.e., no PsA diagnosis during the 1 year before the first observed PsA diagnosis). The earliest date of PsA diagnosis was defined as the index date. Patients with no PsA diagnosis any time during the study period (controls) were directly matched to PsA patients with demographic characteristics. All patients had ≥ 2 years of medical and pharmacy coverage before the index date and ≥ 1 year of follow-up. Incident rates per 100 person-years for comorbidities of interest were evaluated. The hazard ratios of having various comorbid conditions for PsA patients were estimated by Cox proportional hazards models. All-cause and CV-related hospitalizations during the follow-up period were evaluated. RESULTS: A total of 14,898 PsA patients and 35,037 matched controls met the study criteria. Compared with controls, PsA patients had a higher risk of CV disorders (incidence rate = 6.5 vs. 5.8; HR = 1.46; 95% CI = 1.37-1.56) and a higher risk of the majority of the specific CV disorders (hypertension, hyperlipidemia, coronary artery disease, cerebrovascular disease, peripheral vascular disease). PsA patients also had a higher risk for any autoimmune disease (incidence rate = 8.4 vs. 1.6; HR = 18.26; 95% CI = 17.18-19.40) and most autoimmune categories (psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis, and other autoimmune disorders). Rates of other PsA-related comorbidities (diabetes, anxiety, fatigue, smoking, alcohol use, obesity or overweight, depression, osteoporosis, uveitis, eczema, and gout) were also significantly higher for PsA patients. The all-cause hospitalization rate was higher among PsA patients than controls (24.9% vs. 16.2%; P < 0.001). The CV-related hospitalization rate varied depending on whether the CV condition was the primary discharge diagnosis only or was any diagnosis on the inpatient claims. The rates of coronary artery disease hospitalizations were significantly higher in PsA patients than in controls with both methods of analysis (primary diagnosis: 0.8% vs. 0.5%; P < 0.001; nonprimary diagnosis: 3.2% vs. 2.2%; P < 0.001). CONCLUSIONS: This retrospective U.S.-based claims study found that PsA patients had a high comorbidity burden. Compared with the non-PsA population, PsA patients were associated with a higher incidence of CV comorbidities, autoimmune diseases, and other PsA-related comorbidities and a higher rate of all-cause and CV-related hospitalizations. Understanding these comorbidity profiles may provide insight on the effect of comorbid conditions on disease management and health care utilization associated with PsA. DISCLOSURES: This study was funded by Novartis. Kaine is a paid consultant for Novatis. Hur and Palmer are Novartis employees and stockowners. Song and Kim work for Truven Health Analytics, which received funding from Novartis to conduct this study.
29873000 Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmun 2018 Aug INTRODUCTION: The molecular and pharmacological complexity of biologic disease-modifying antirheumatic drugs used for the management of rheumatoid arthritis (RA) favors the occurrence of adverse drug reactions (ADRs), which should be constantly monitored in post-marketing safety studies. OBJECTIVE: The aim of this study was to identify signals of disproportionate reporting (SDR) of clinical relevance related to the use of biologic drugs approved for RA and other autoimmune diseases. METHODS: All suspected ADRs registered in the FDA Adverse Event Reporting System between January 2003 and June 2016 were collected. The reporting odds ratio was used as a measure of disproportionality to identify possible SDRs related to biologics. Those involving important medical events and designated medical events (DME) were prioritized. RESULTS: In total, 2602 SDRs were prioritized. The most commonly reported were 'Infections and infestations' (32.2%) and 'Neoplasms benign, malignant, and unspecified' (20.4%), and were mainly related to use of infliximab (25.3%, p < 0.001, and 28.8%, p = 0.002, respectively). Sixty-three signals involving DMEs were identified, most of which were related to rituximab (n = 27), and were mainly due to 'blood disorders'. Amongst the DMEs detected for more than one biologic, 'intestinal perforation' and 'pulmonary fibrosis' were related to most of them. CONCLUSIONS: The results of this study highlight possible safety issues associated with biologics, whose relationship should be more thoroughly investigated. Our results contribute to future research on the identification of clinically relevant risks associated with these drugs, and may help contribute to their rational and safe use.
30282544 Motec Wrist Arthroplasty: 4 Years of Promising Results. 2018 Sep BACKGROUND: The Motec cementless modular metal-on-metal ball-and-socket wrist arthroplasty is an implant with promising intermediate results. An alternative to primary wrist fusion, total wrist arthroplasty is an option for active patients, who wish to retain their wrist function. It is indicated in cases of degenerative osteoarthritis, post-traumatic arthritis and rheumatoid (inflammatory) arthritis. METHODS: A prospective review of patient demographics, pre and post-operative Disabilities of the Arm Shoulder and Hand (DASH), MAYO scores, range of movements and grip strengths. All complications in follow up were recorded across the 4 year period. RESULTS: 25 implants on 23 patients over 5.5 years, mean age 61; 8 females and 15 male. 10 patients with SLAC, 3 SNAC, 5 inflammatory and 7 patients with generalized osteoarthritis. The patients showed significant improvements of MAYO and DASH scores post-operatively, as well as the flexion/extension arc and grip strengths. There was just one case of implant loosening- the radial screw after a wound infection, which was revised with a longer screw. Two implants were converted to Motec fusion due to pain. One implant was dislocated and relocated. The remaining patients have had good wrist function. Only 6 patients were unable to return to work. CONCLUSIONS: Similar to published studies, this series shows the Motec implant to be a good motion preserving alternative to total wrist fusion.
28973840 Patterns of Biologics Utilization and Discontinuation Before and During Pregnancy in Women 2018 Jul OBJECTIVE: To characterize patterns of biologics use and discontinuation before and during pregnancy in women with autoimmune diseases in British Columbia, Canada. METHODS: Women with ≥1 autoimmune diseases, as identified by International Classification of Diseases Ninth/Tenth Revision codes, who had pregnancies ending in deliveries between January 1, 2002, and December 31, 2012, and had ≥1 prescription for a biologic drug 1 year before pregnancy or during pregnancy, were included. Secular trends, patterns of biologics use, and risk of biologics discontinuation before and during pregnancy were examined. Associations between drug discontinuations and various factors were investigated using multilevel logistic regression models, fitted with binomial generalized estimating equations. RESULTS: Of 6,218 women (8,431 pregnancies) with autoimmune diseases, 131 women (144 pregnancies) were exposed to a biologic before or during pregnancy. The use of biologics in this cohort increased from 0% in 2002 to 5.7% by 2012 (P < 0.001). Within the first trimester of pregnancy, 31% of women (34/110) discontinued their biologic treatment, and 38% (30/79) discontinued use in the second trimester, while 98% of those receiving treatment in the second trimester (50/51) continued treatment in the third trimester. Women with rheumatoid arthritis had three times higher odds (odds ratio 3.40 [95% confidence interval 1.33-8.71]) of discontinuing biologics during pregnancy, compared to those with inflammatory bowel disease. CONCLUSION: Given the increased use of biologics and high odds of discontinuation during pregnancy in certain populations, more research is needed to improve our understanding of the risks and benefits of biologics for fetal and maternal health.