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31211114 Morbidity and mortality in patients with rheumatoid arthritis compared with an age- and se 2019 Jan OBJECTIVE: The aim of this study was to examine the prevalence of morbidity and mortality in patients with seropositive rheumatoid arthritis (RA). METHODS: Data were obtained from national population-based registries in the period 1998-2009. Prior to the seropositive RA diagnosis (International Classification of Disorders 10th revision M05), we identified a total of 21,558 patients and 87,384 age- and sex-matched control subjects. Odds for morbidity were calculated before and after the RA diagnosis. We estimated the overall survival based on the Kaplan-Meier method. RESULTS: Patients with RA had statistically significantly higher odds for a number of co-morbidities prior to the onset of RA including diseases of the musculoskeletal system (odds ratio (OR) 3.10, 95% confidence interval (CI) 3.00-3.21), diseases involving the immune system (OR 1.45, 95% CI 1.29-1.64), endocrine diseases (OR 1.09, 95% CI 1.01-1.17), diseases of the circulatory system (OR 1.08, 95% CI 1.03-1.14) and diseases of the respiratory system (OR 1.30, 95% CI 1.22-1.38), compared with age- and sex-matched control subjects. After the RA diagnosis, the same trend was seen with higher odds for the same co-morbidities. We found a 5-year survival of 80% (95% CI 78-81%) for patients with RA, while for control subjects it was 88% (95% CI 88-89%). CONCLUSION: Compared with age- and sex-matched controls, patients with seropositive RA have higher odds for several co-morbidities prior to and, particularly, after the diagnosis of RA. Furthermore, patients with RA have a lower overall survival compared with age- and sex-matched controls.
31902746 Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by De 2020 Mar 6 Accumulating evidence suggests long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Here, we aimed to define the role of HOXA transcript at the distal tip (HOTTIP) in RA pathogenesis in relation to SFRP1 methylation and Wnt signaling pathway. HOTTIP was found highly expressed, and SFRP1 was hypermethylated in RA synovial fibroblasts (RASFs). Next, gain- or loss-of-function experiments were conducted in RASFs to explore the effects of HOTTIP on the biological behaviors of RASFs. Silencing of HOTTIP or overexpression of SFRP1 inhibited RASF proliferation, invasion, and migration, while enhancing apoptosis. The relationship among HOTTIP, SFRP1, and Dnmt3b was determined using methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), RNA pull-down, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays. The regulatory mechanisms of HOTTIP/Dnmt3b/SFRP1 were explored by altering their expression in RASFs. It was noted that HOTTIP could induce SFRP1 promoter methylation through recruitment of Dnmt3b and activate the Wnt signaling pathway. Finally, a rat RA model was established in order to evaluate the in vivo effects of HOTTIP and SFRP1, which suggested that HOTTIP silencing or SFRP1 elevation inhibited the progression of RA in vivo. Our key findings demonstrate the anti-inflammatory ability of HOTTIP silencing in RA through SFRP1 promoter demethylation. These findings support HOTTIP as a candidate anti-arthritis target.
31832330 Self-Efficacy and the Role of Non-Pharmacologic Treatment Strategies to Improve Pain and A 2019 Jun 15 PURPOSE OF REVIEW: There is increasing evidence that adjunctive, non-pharmacologic treatment programs are beneficial in the management of arthritis when added to traditional disease-modifying medications. This review focuses on non-pharmacologic management strategies that impact pain and affect, with a focus on self-efficacy, for those with osteoarthritis (OA) and rheumatoid arthritis (RA). RECENT FINDINGS: We reviewed both office-based and internet-based self-management strategies, mindfulness based interventions (MBIs), and cognitive behavioral therapies (CBTs) for patients with arthritis. These behavioral strategies have shown to improve pain, mood disturbance, and physical function in those with both osteoarthritis and rheumatoid arthritis. Improvements in self-efficacy and coping capacity are associated with improvements in patient-reported outcomes (PROs) related to pain and functioning. SUMMARY: Self-management programs, MBIs, and CBTs are more effective at improving pain and mood disturbance compared to usual care for patients with arthritis although high quality randomized controlled trials are lacking. Non-pharmacologic management programs are increasingly available via the internet and mobile applications.
31404889 Cholinergic system is involved in the therapeutic effect of madecassoside on collagen-indu 2019 Oct Our previous studies demonstrated that oral administration of madecassoside could markedly attenuate collagen-induced arthritis in rats, a rodent model of rheumatoid arthritis. As the autonomic nervous system is critically involved in the modulation of peripheral inflammation and immune response, the present study aims to explore the possible involvement of adrenergic and cholinergic nerves in the effect of madecassoside on rheumatoid arthritis. Arthritis was induced by chicken collagen in rats, and madecassoside was orally administered daily for two weeks from day 14 after the primary immunization. The antagonists of adrenoceptor and cholinergic receptors were co-administered with madecassoside, respectively. Unilateral cervical vagotomy was performed four days before the arthritis induction. The results showed that madecassoside (30 mg/kg) treatment markedly ameliorated arthritis symptoms in rats, mainly evidenced by the reduction of paw swelling and arthritis index scores. Co-administration of madecassoside with atropine (an antagonist of the muscarinic acetylcholine receptor) or hexamethonium (an antagonist of the nicotinic acetylcholine receptor) markedly diminished the therapeutic effects of madecassoside in arthritis. However, co-administration with phentolamine (an antagonist of the α-adrenoceptor) or propranolol (an antagonist of the β-adrenoceptor) did not alter the effect of madecassoside on arthritis. Furthermore, unilateral cervical vagotomy significantly reduced the anti-arthritis efficacy of madecassoside, including the amelioration of clinical symptoms, as well as the inhibition of the production of pro-inflammatory cytokines except T lymphocytes-related cytokines. These findings suggest that madecassoside exerts inhibitory effects on collagen-induced arthritis through, at least partially, the peripheral cholinergic system.
30954617 Protective effects of Wang-Bi tablet on bone destruction in collagen-induced arthritis by 2019 Jun 28 ETHNOPHARMACOLOGICAL RELEVANCE: Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear. AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism. MATERIALS AND METHODS: DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37  g/kg/d) or WB at a lower (1.11  g/kg/d, WBL) or higher dose of (3.33  g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined. RESULTS: Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice. CONCLUSION: Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.
30609724 Hyaluronic Acid Coated Acid-Sensitive Nanoparticles for Targeted Therapy of Adjuvant-Induc 2019 Jan 2 Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of -2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.
30707391 Adverse Events in Giant Cell Arteritis and Rheumatoid Arthritis Patient Populations: Analy 2019 Mar INTRODUCTION: The safety profile of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) is well established. TCZ was approved to treat giant cell arteritis (GCA) in 2017 in the USA and Europe, and its safety profile in patients with GCA continues to be defined. The objective of this analysis was to examine incidence rates (IRs) of adverse events of special interest (AESI) occurring during the TCZ clinical development program and in healthcare claims data in patients with GCA or RA. METHODS: TCZ-naïve patients with GCA or RA were identified in the MarketScan administrative healthcare claims database. TCZ-treated patients with GCA from the GiACTA trial and TCZ-treated patients with RA from pooled clinical trial data were analyzed. The IRs of AESI (AESI IRs) were calculated for all cohorts. In the claims cohorts, risks of AESI were estimated using Poisson regression. RESULTS: TCZ-naïve claims cohorts comprised 4804 patients with GCA [mean (standard deviation) age 73.4 (9.8) years; follow-up 3.9 (3.1) years] and 15,164 patients with RA [age 60.3 (8.2) years; follow-up, 4.5 (2.8) years]. TCZ-treated clinical trial cohorts comprised 149 patients with GCA [age 69.5 (8.4) years; exposure approx. 138 patient-years (PY)] and 7647 with RA [age 52 (12.6) years; exposure approx. 22,394 PY]. The IRs of infections, stroke, malignancies, myocardial infarction, and gastrointestinal perforations in the GCA claims cohort exceeded those in the RA claims cohort; the risk of AESI (adjusted for age and glucocorticoid use) was higher in patients with GCA than in those with RA. Similar patterns to the claims cohorts in terms of the AESI IRs were observed in clinical trial cohorts, although the number of events was limited in the GCA trial cohort. CONCLUSION: Higher IRs of AESI were observed in patients with GCA versus those with RA in both TCZ-naïve and -treated cohorts. Differences in underlying disease, age, and glucocorticoid use may influence AESI incidence, irrespective of intervention. FUNDING: This study was funded by F. Hoffmann-La Roche Ltd and Genentech, Inc. Article processing charges were funded by F. Hoffmann-La Roche Ltd. Plain language summary is available for this article.
30424593 Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with 2019 Apr STUDY DESIGN: Retrospective case-control study, level 4. PURPOSE: To clarify the risk factors for late subaxial lesion after occipitocervical (O-C) reconstruction. We examined cases requiring fusion-segment-extended (FE) reconstruction in addition to/after O-C reconstruction. OVERVIEW OF LITERATURE: Patients with rheumatoid arthritis (RA) frequently require O-C reconstruction surgery for cranio-cervical lesions. Acceptable outcomes are achieved via indirect decompression using cervical pedicle screws and occipital plate-rod systems. However, late subaxial lesions may develop occasionally following O-C reconstruction. METHODS: O-C reconstruction using cervical pedicle screws and occipital plate-rod systems was performed between 1994 and 2007 in 113 patients with RA. Occipito-atlanto-axial (O-C2) reconstruction was performed for 89 patients, and occipito-subaxial cervical (O-under C2) reconstruction was performed for 24 patients. We reviewed the cases of patients requiring FE reconstruction (fusion extended group, FEG) and 26 consecutive patients who did not require FE reconstruction after a follow-up of >5 years (non-fusion extended group, NEG) as controls. RESULTS: FE reconstructions were performed for nine patients at an average of 45 months (range, 24-180 months) after O-C reconstruction. Of the 89 patients, three (3%) underwent FE reconstruction in cases of O-C2 reconstruction. Of the 24 patients, five (21%) underwent FE reconstruction in cases of O-under C2 reconstruction (p=0.003, Fisher exact test). Age, sex, RA type, and neurological impairment stage were not significantly different between FEG and NEG. O-under C2 reconstruction, larger correction angle (4° per number of unfixed segment), and O-C7 angle change after O-C reconstruction were the risk factors for late subaxial lesions on radiographic assessment. CONCLUSIONS: Overcorrection of angle at fusion segments requiring O-C7 angle change was a risk factor for late subaxial lesion in patients with RA with fragile bones and joints. Correction should be limited, considering the residual mobility of the cervical unfixed segments.
32743499 Paradoxical role of Breg-inducing cytokines in autoimmune diseases. 2019 Dec Regulatory B cells (Breg) are crucial immunoregulators that maintain peripheral tolerance and suppress inflammatory autoimmune responses. In recent years, our understanding on the nature and mechanism of action of Bregs has revealed the important role of cytokines in promoting the regulatory properties of this unique B cell subset, both in animal and human models. In this review, we compiled the cytokines that have been reported by multiple studies to induce the expansion of Breg. The Breg-inducing cytokines which are currently known include IL-21, IL-6, IL1β, IFNα, IL-33, IL-35, BAFF and APRIL. As cytokines are also known to play a pivotal role in the pathogenesis of autoimmune diseases, in parallel we reviewed the pattern of expression of the Breg-inducing cytokines in Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Inflammatory Bowel Diseases (IBD) and Multiple Sclerosis (MS). We show here that Breg-inducing cytokines are commonly implicated in these inflammatory diseases where they typically have a higher expression than in healthy individuals, suggesting their paradoxical nature. Interestingly, despite the general overexpression of Breg-inducing cytokines, it is known that Breg cells are often numerically or functionally impaired in various autoimmune conditions. Considering these alterations, we explored the possible parameters that may influence the function of Breg-inducing cytokines in exhibiting either their regulatory or pro-inflammatory properties in the context of autoimmune conditions.
30911211 Surgical Treatment of Tenosynovitis of Extensor Tendons of Fourth Compartment of Wrist in 2019 Apr Purpose Proliferative tenosynovitis of the extensor tendons is a very common painful wrist condition that can occur both in presence and absence of rheumatoid arthritis (RA). This study aims to evaluate a series of patients without RA, having extensor tendon tenosynovitis, its pathology, and results of surgical treatment. Materials and Methods A consecutive series of 10 patients without RA, having tenosynovitis of fourth extensor compartment were treated surgically and evaluated in the study. All patients were operated upon by a single surgeon, and intraoperative specimens were sent for histopathologic evaluation by a single pathologist. The functional outcome of the patients was evaluated by comparing the post- and preoperative wrist extension. Results All patients presented with painful mass over dorsum of the wrist, overlying the fourth extensor compartment. On clinical examination, there was severe limitation of active wrist extension with extended fingers and improvement in wrist extension on flexing the fingers. All patients had significant improvement in wrist extension after surgery. The histopathologic examination of the intraoperative samples revealed similar findings of tenosynovitis in all cases, which was different than that seen in RA. Conclusion This study reveals a distinct tenosynovitis in a group of patients without RA resembling traumatic tenosynovitis on histopathologic examination. Radiologic and intraoperative findings reveal presence of nodular mass in the affected tendon due to proliferative tenosynovitis, which blocks effective proximal excursion of the tendon, leading to decreased wrist extension. This study shows that surgical treatment in the form of tenosynovectomy gives excellent relief to these patients. Type of Study This is a Level IV, therapeutic study.
31548745 Tofacitinib in the treatment of active rheumatoid arthritis - single-centre experience. 2019 OBJECTIVES: To assess the efficacy and safety profile of tofacitinib taken orally at a dose of 10 mg/day in patients with severe active rheumatoid arthritis (RA). MATERIAL AND METHODS: The retrospective observational study included 10 patients (6 women and 4 men) with RA treated with tofacitinib. All the patients had high disease activity (DAS28 [ESR] > 5.1), despite therapy with two synthetic disease-modifying antirheumatic drugs (DMARDs). Before the initiation of treatment, routine laboratory tests were performed, and disease activity was assessed in all the subjects. RESULTS: The mean age of the patients in the study group was 58.18 years (43-67). The average duration of RA was 9.9 years (2-24). The mean baseline value of DAS28 (ESR) was 6.37. Tofacitinib was used in combination with a conventional DMARD in all study subjects: with methotrexate in the majority of patients, and with leflunomide and an antimalarial drug in three patients. The mean duration of therapy with tofacitinib was 7.57 months (3.9-10.8). A significant decrease in the disease activity was observed (p < 0.05). A reduction in DAS28 (ESR) score was seen already after the first month of therapy, and the trend was maintained during subsequent months of follow-up. The mean value of DAS28 (ESR) after 6 months was 2.78. A slight increase in the serum concentration of HDL cholesterol was observed during treatment. In one patient symptoms of chronic upper respiratory tract infection led to discontinuation of the drug. The observed adverse events were of mild/moderate degree. CONCLUSIONS: The results of our retrospective observational study conducted in the setting of daily clinical practice confirm a good clinical response to tofacitinib. Despite the observed adverse effects, in the light of the available data tofacitinib demonstrates a favourable safety profile. JAK kinase inhibitors - a new class of drugs - will enable a wider population of patients to achieve remission or low disease activity.
31298001 [Effectiveness of total elbow arthroplasty with preservation of triceps brachii insertion 2019 Jul 15 OBJECTIVE: To investigate the effectiveness of total elbow arthroplasty (TEA) with preservation of triceps brachii insertion approach. METHODS: Between January 2012 and September 2017, 17 patients with elbow disease were treated with TEA with preservation of triceps brachii insertion approach. There were 3 males and 14 females, with an average age of 65.2 years (range, 48-85 years). The injuries located on left elbow in 5 cases and on right elbow in 12 cases. There were 11 cases of distal humerus fracture (AO type C1 in 2 cases and type C3 in 9 cases); the interval between fracture and operation was 3-10 days (mean, 4.1 days). There were 3 cases of osteoarthritis and 3 cases of rheumatoid arthritis, with the disease duration of 2-26 years (mean, 8.7 years). The postoperative elbow function and pain was assessed by Mayo elbow performance score (MEPS) and visual analogue scale (VAS) score, respectively. The prosthesis position, heterotopic ossification, and periprosthetic fracture were observed by X-ray films. RESULTS: All incisions healed by first intention. Sixteen patients were followed up 18-69 months (mean, 40.6 months). Intraoperative ulnar nerve injury occurred in 2 cases, and healed after symptomatic treatment. At last follow-up, the MEPS score was 55-100 (mean, 90.3). The results were excellent in 11 cases, good in 2 cases, fair in 2 cases, and poor in 1 case, with an excellent and good rate of 81.3%. The VAS score was 0-2 (mean, 0.4). X-ray reexamination showed that no polyethylene wear, prosthesis loosening and fracture, abnormal prosthesis position, periprosthetic fracture occurred during the follow-up period, and the prosthesis survival rate was 100%. Heterotopic ossification occurred in 2 and 3 months after operation in 2 cases, respectively. CONCLUSION: The triceps on approach for TEA are satisfactory for distal humerus fracture, osteoarthritis, and rheumatoid arthritis.
31878151 Surgical Treatment for the Ankle and Foot in Patients with Rheumatoid Arthritis: A Systema 2019 Dec 24 The aim was to identify effective surgical treatments for patients with rheumatoid arthritis in the foot and/or ankle. A systematic review of the literature was conducted via a data search of the PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PROSPERO databases, from their inception until June 2019. Only non-randomized controlled trials and cohort studies were included in this review. Two of the present authors independently assessed the quality of each study and extracted the relevant data. A quality assessment of all articles was performed using the methodological index for non-randomized studies criteria. In addition, the Newcastle Ottawa scale was used for cohort studies. Thirteen studies met the inclusion criteria (five cohort studies and eight NRCTs). The total population considered was 923 patients (570 patients had RA), with a mean age of 58.8 years. Regarding the risk of bias, both the NRCTs and the cohort studies had a moderate level of quality. Despite the relatively low quality of these studies, surgical treatment for the foot and/or ankle is shown to reduce pain and improve functionality in patients with RA, in the short term (6-12 months).
31673680 The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis. 2019 BACKGROUND: The prevalence of mood disturbances such as anxiety and depression is greater in rheumatoid arthritis (RA) patients than in the general population. Given this association, the primary aim of this study was to assess the incremental impact of anxiety or depression on patients with RA from the United States of America (USA) and Europe, independent of the impact of the underlying RA disease. METHODS: Rheumatologists (n = 408) from the USA and 5 European countries completed patient record forms for a predetermined number of RA patients who consulted consecutively during the study period; these patients completed patient-reported questionnaires. Descriptive statistics and multivariate regression were used to investigate the relationship between anxiety and depression with treatment and economic outcomes in RA patients. RESULTS: Of 1015 physician and patient pairs who completed all relevant questionnaire sections, 390 (38.4%) patients self-reported anxiety or depression, while 180 (17.7%) patients were reported to have anxiety or depression by their physicians. Controlling for age, gender, body mass index and clinical factors (flaring and severity), multiple regression analyses suggested that patients with anxiety or depression more often experienced treatment dissatisfaction (odds ratio [OR] 2.28; P < .001), had greater impairment in work (coefficient [β] = 11.82; P = .001) and usual activity (β = 14.73; P < .001), greater disability (β = .35; P < .001), and more often reported unemployment (OR 1.74; P = .001). Multinomial logistic regression revealed discordance between physician and patient satisfaction with treatment. For patients reporting anxiety or depression, physicians were more often satisfied with achievement of current disease control than patients (relative risk ratio 2.19; P = .002). CONCLUSION: Concomitant anxiety or depression was associated with a significant incremental impact on the health-related quality of life and economic aspects of life of patients with RA. In light of observed differences between physician recognition of patient anxiety and/or depression versus patient reporting of anxiety and/or depression symptoms, further research is warranted to develop optimal screening and management of depression and anxiety in patients with RA.
30632015 Tocilizumab Effectiveness After Switching from Intravenous to Subcutaneous Route in Patien 2019 Mar INTRODUCTION: The main objective of this work was to assess the maintenance of effectiveness of subcutaneous tocilizumab 6 months after switching from intravenous to subcutaneous formulation in patients with rheumatoid arthritis (RA) in a real-world setting. Secondary objectives aimed to describe the characteristics of patients and disease, the effectiveness at 12 months after switching, the therapeutic maintenance, and to search for predictive factors of switching. METHODS: We analyzed all the RA patients of the shared medical file "RIC Nord de France", treated with tocilizumab, switching or not from intravenous to subcutaneous tocilizumab, between April 2015 and January 2016. The primary effectiveness endpoint was the proportion of patients remaining in their DAS28-ESR category remission/low disease activity (LDA) or moving to an inferior DAS28-ESR category at 6 months. Since RoSwitch was an observational study, without randomization, a propensity score was built in a sensitivity analysis to balance on RA and patients' characteristics at inclusion between switching and no-switching groups. RESULTS: An improvement of initial DAS28-ESR category or maintenance in DAS28-ESR remission/LDA at 6 months was shown in 203 of the 285 patients with an evaluation for the primary criterion (71.2%, 95% CI [65.6-76.4%]) without differences between groups (73.3%, 95% CI [63.0-82.1%] vs. 70.3%, 95% CI [63.3-76.6%]). The RoSwitch study showed the maintenance of effectiveness at 6 and 12 months. Similar therapeutic maintenance rates were observed for switch and no-switch patients. No clinical factor was associated with the switch in patients in remission/LDA at inclusion. CONCLUSIONS: The RoSwitch study showed the maintenance of effectiveness at 6 months in RA patients switching from intravenous (IV) to subcutaneous (SC) tocilizumab. FUNDING: Roche SAS and Chugai Pharma France.
30997066 A case of palisaded neutrophilic granulomatous dermatitis with subsequent development of c 2019 Apr Palisaded neutrophilic granulomatous dermatitis is a cutaneous marker of a systemic disease. Clinicians' goal should be directed toward determining an underlying condition. Even if the initial investigation is inconclusive, it may be necessary that some tests are repeated, since a serious underlying disease could be revealed in the course of time.
31380381 Mercury Is Taken Up Selectively by Cells Involved in Joint, Bone, and Connective Tissue Di 2019 Background: The causes of most arthropathies, osteoarthritis, and connective tissue disorders remain unknown, but exposure to toxic metals could play a part in their pathogenesis. Human exposure to mercury is common, so to determine whether mercury could be affecting joints, bones, and connective tissues we used a histochemical method to determine the cellular uptake of mercury in mice. Whole neonatal mice were examined since this allowed histological assessment of mercury in joint, bone, and connective tissue cells. Materials and Methods: Pregnant mice were exposed to a non-toxic dose of 0.5 mg/m(3) of mercury vapor for 4 h a day on gestational days 14-18. Neonates were sacrificed at postnatal day 1, fixed in formalin, and transverse blocks of the body were processed for paraffin embedding. Seven micrometer sections were stained for inorganic mercury using silver nitrate autometallography, either alone or combined with CD44 immunostaining to detect progenitor cells. Control neonates were not exposed to mercury during gestation. Results: Uptake of mercury was marked in synovial cells, articular chondrocytes, and periosteal and tracheal cartilage cells. Mercury was seen in fibroblasts in the dermis, aorta, esophagus and striated muscle, some of which were CD44-positive progenitor cells, and in the endothelial cells of small blood vessels. Mercury was also present in renal tubules and liver periportal cells. Conclusions: Mercury is taken up selectively by cells that are predominantly affected in rheumatoid arthritis and osteoarthritis. In addition, fibroblasts in several organs often involved in multisystem connective tissue disorders take up mercury. Mercury provokes the autoimmune, inflammatory, genetic, and epigenetic changes that have been described in a range of arthropathies and bone and connective tissue disorders. These findings support the hypothesis that mercury exposure could trigger some of these disorders, particularly in people with a genetic susceptibility to autoimmunity.
30304717 Pregnancy Outcomes of Patients Exposed to Adalimumab in Japan. 2019 BACKGROUND: This is the first retrospective report of pregnancy outcomes after exposure to adalimumab treatment in Japan. METHODS: Using the AbbVie safety database, we analyzed pregnancy outcome data from patients who received adalimumab treatment from April 16, 2008, to May 15, 2017. RESULTS: Data were extracted retrospectively for 74 pregnancies in 73 patients. More than half of the patients included in the study received adalimumab for the treatment of Crohn's disease (37.8%) or ulcerative colitis (20.3%), while 9.5% received adalimumab for rheumatoid arthritis. Of the 53 pregnancies with available outcome data, 45 newborns (45/53 [84.9%]) were delivered. Of these births, 30 were full-term, 2 were preterm, and 13 were unknown. Apgar scores were available for 11 of the 16 newborns whose mothers were exposed to adalimumab in the third trimester; all scores were within the normal range. Low birth weight was observed in 5 infants out of the 30 full-term deliveries. There were also 5 miscarriages (5/53 [9.4%]), 2 induced abortions (2/53 [3.8%]), and 1 stillbirth (1/53 [1.9%]). Eight maternal adverse events were observed in 5 pregnancies; no serious adverse events occurred. CONCLUSION: Although safety concerns were inconclusive, these data do not report additional risk to pregnancy outcomes with adalimumab exposure.
30084704 Quantification of Ocular Biomechanics In Ocular Manifestations of Systemic Autoimmune Dise 2019 Purpose: To quantify biomechanical change associated with autoimmune diseases using Corvis ST deformation data. Methods: Cross-sectional, observational, case control study of 76 patients with systemic autoimmune disease and 21 control subjects. All patients underwent detailed ophthalmic examination with Corvis-ST (Oculus Optikgerate Gmbh, Germany) measurements for biomechanical properties of the eye. Corneal deformation and also deformation caused by the extracorneal tissue were recorded. Using a mathematical formula, the three parameters, namely, corneal stiffness (kc), extracorneal tissue stiffness (kg), and extracorneal tissue viscosity (μg), were defined. Results: The biomechanical analysis showed that kc and μg were significantly lower in patients with systemic autoimmune disease with eye manifestations than control group. However statistically, it was significant in rheumatoid arthritis (RA) patients only. Conclusion: The new parameters, namely, kc, kg, and μg, can provide a sensitive marker of the ocular activity of the collagen vascular diseases.
33458667 Joint Surgery in Tunisian Rheumatoid Arthritis Patients: Prevalence and Risk Factors. 2020 Sep OBJECTIVES: This study aims to assess the prevalence of joint surgery in Tunisian patients with rheumatoid arthritis (RA) and to determine the risk factors of surgical treatment. PATIENTS AND METHODS: This retrospective cross-sectional study was performed over a period of 15 years between January 2000 and December 2014 and included 500 Tunisian patients with RA (78 males, 422 females; mean age 53.4 years; range, 21 to 83 years). The prevalence of joint surgery indication was evaluated. Clinical, paraclinical and therapeutic characteristics of RA were compared according to the need of surgery. RESULTS: Female to male ratio was 5. The indication of joint surgery was noted in 59 patients (12%). Knee joint surgery was the most performed surgical procedure (56% of surgical treatment). A decrease in surgery prevalence from 30% in 2004 to 4% in 2013 was noted. Statistical study showed that factors associated with joint surgery were: delayed diagnosis (p=0.037), long RA duration (p=0.017), young onset of RA (p<0.001), presence of joint deformities (p=0.034), presence of osteoporosis (p=0.029), presence of antinuclear antibodies (p<0.001), combination therapy of methotrexate with other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (p=0.001), short period of first medical treatment (p=0.012) and high erythrocyte sedimentation rate (ESR) (p=0.027). In multivariate analysis, three factors were independently related to the use of joint surgery: age at disease onset [odds ratio (OR): 2.799 95% confidence interval (CI): 1.49-5.22; p=0.01], high ESR level (OR: 2.807 95% CI: 1.5-5.24; p=0.01) and association of methotrexate with other csDMARDs (OR: 3.500 95% CI: 1.61-7.56; p=0.01). CONCLUSION: Twelve percent of RA patients needed joint surgical treatment. Predictive factors of surgery were age at disease onset, high ESR level and association of methotrexate with other csDMARDs.