Browse

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

ID PMID Title PublicationDate abstract
31565005 Quality of life in Ecuadorian patients with established rheumatoid arthritis. 2019 PURPOSE: To evaluate quality of life in patients with established rheumatoid arthritis (RA) and identify the factors that negatively affect it. METHODS: This was a cross-sectional study with patients with established RA from a rheumatology center in Ecuador. The RA Quality of Life (RAQoL) questionnaire was used to assess QoL and the Health Assessment Questionnaire - disability index (HAQ-DI) questionnaire for functional capacity. In addition, demographics, clinical characteristics, and markers of disease activity were included. Data were analyzed using SPSS 22. RESULTS: Of 186 patients, 89.8% were women, with a mean age of 51 years, 86.6% had symmetrical polyarticular involvement, 40.3% erosions, 46.8% morning stiffness, 46.8% xerophthalmia, and 39.2% fatigue. Depression was the most frequent comorbidity - 42.5%. The mean HAQ-DI score was 0.8, and 26.9% had functional disability. The mean RAQoL score was 7.2. Xerophthalmia, xerostomia, fatigue, morning stiffness, and depression were related to higher scores in the RAQoL (p<0.05). The mean RAQoL was higher in patients with more disease activity and comorbidities (p<0.05). Likewise, patients with functional disability had a mean RAQoL score of 15.6 versus 4.1 in patients without disability (p<0.05). There were positive correlations between RAQoL and ESR, CRP, painful-joint count, swollen-joint count, VAS of pain, and physician assessment (p<0.05). CONCLUSION: QoL is severely affected in patients with RA. Depression, fatigue, morning stiffness, pain, high disease activity, and disability have a negative effect on QoL in RA. Likewise, patients with more comorbidities and extraarticular manifestations show worse QoL.
31392874 Upper Cervical Subluxation and Cervicomedullary Junction Compression in Patients with Rheu 2019 Nov OBJECTIVE: Rheumatoid arthritis (RA) is known to involve the cervical spine up to 86%. It often causes cervical instability like atlantoaxial subluxation (AAS), subaxial subluxation, and vertical subluxation (VS). In order to find the relation between RA and cord compression, we will evaluate the characteristics and risk factors of basilar invagination (BI) and cervicomedullary junction (CMJ) compression. METHODS: From January 2007 to May 2015, 12667 patients administrated to Hanyang University Medical Center. Four thousand three hundred eighty-six patients took cervical X-ray and 250 patients took cervical computed tomography or magnetic resonance imaging. Radiologic parameters, medication records were obtained from 242 patients. Multivariate logistic regression analysis was performed with correlation of CMJ compression, basin-dental interval (BDI), basin-posterior axial line interval (BAI), pannus formation, BI, and AAS. RESULTS: In the point of CMJ compression, atlantodental interval (ADI), posterior-atlantodental interval, BAI, AAS, and BI are relatively highly correlated. Patients with BI have 82 times strong possibility of radiologic confirmed CMJ compression, while AAS has 6-fold and pannus formation has the 3-fold possibility. Compared to the low incidence of BI, AAS and pannus formation have more proportion in CMJ compression. Furthermore, wrist joint erosion was correlated with VS and AAS. CONCLUSION: BI has a very strong possibility of CMJ compression, while AAS and pannus formation have a high proportion in CMJ compression. Hence bilateral wrist joint erosion can be used as an indicator for the timing of screening test for cervical involvement. We suggest the early recommendation of cervical spine examination for the diagnosis of cervical involvement in order to prevent morbidity and mortality.
30825220 MicroRNA and exosome: Key players in rheumatoid arthritis. 2019 Mar 1 Rheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis.
31360633 Marked deterioration in rheumatoid arthritis associated bronchiectasis following treatment 2019 We report a 67 year old lady with Rheumatoid Arthritis (RA) and mild bronchiectasis (BE) whose treatment was escalated to Rituximab. Nine months after commencing Rituximab her lung sepsis worsened dramatically with repeated hospitalization, new sputum isolation of Stenotrophomonas maltophilia and Pseudomonas aeruginosa and marked radiological deterioration in BE. She was found to have a low serum IgG and IgM levels almost certainly as a complication of Rituximab. Immunoglobulin replacement therapy was instituted and her clinical status has slowly improved.
32010886 Is Radial Deviation of Wrist Related With Median Nerve Swelling in Patients With Rheumatoi 2019 Dec OBJECTIVES: This study aims to investigate whether or not radial deviation developing after wrist involvement of rheumatoid arthritis (RA) is a cause of median nerve swelling. PATIENTS AND METHODS: The study included 51 RA patients (12 males, 39 females; mean age 50.9±8.9 years; range, 18 to 65 years) without carpal tunnel syndrome (CTS) detected by electroneuromyography. Duruöz hand index, visual analog scale, and painDETECT questionnaire were performed in clinical assessment. Radiographic measurements including radial inclination (RI) angle were performed. Using ultrasonography, the median nerve cross-sectional areas (CSAs) were measured from the four levels of the distal one third of the forearm, radioulnar joint, pisiform bone, and hook of hamate, while the ulnar nerve CSAs were measured from the pisiform bone. RESULTS: The study was completed with 102 hands of 51 patients. A negative correlation was found between the RI and the median CSAs measured from the radioulnar joint (R=-0.49; p=0.00), the pisiform bone (R= -0.45; p=0.00), and hook of hamate (R= -0.60, p=0.00). When the hands were divided into three groups according to the ranges of RI specified in the literature, the median nerve CSA was found to be significantly higher in the group with low RI at these levels (p<0.001). CONCLUSION: In patients with RA without CTS, the increase in the median nerve CSAs may be associated with radiographic measures such as radial deviation.
31938731 Effects of monthly minodronate with or without eldecalcitol addition in osteoporosis patie 2019 Dec OBJECTIVES: Increasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. METHODS: The cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. RESULTS: Baseline values were comparable between the groups apart from a tendency for higher TRACP-5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. CONCLUSIONS: The above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.
30686971 A Comparison of Co-methylation Relationships Between Rheumatoid Arthritis and Parkinson's 2018 Rheumatoid arthritis (RA) is a complex autoimmune disease. Recent studies have identified the DNA methylation loci associated with RA and found that DNA methylation was a potential mediator of genetic risk. Parkinson's disease (PD) is a common neurodegenerative disease. Several studies have indicated that DNA methylation levels are linked to PD, and genes related to the immune system are significantly enriched in PD-related methylation modules. Although recent studies have provided profound insights into the DNA methylation of both RA and PD, no shared co-methylation relationships have been identified to date. Therefore, we sought to identify shared co-methylation relationships linked to RA and PD. Here, we calculated the Pearson's correlation coefficient (PCC) of 225,239,700 gene pairs and determined the differences and similarities between the two diseases. The global co-methylation change between in PD cases and controls was larger than that between RA cases and controls. We found 337 gene pairs with large changes that were shared between RA and PD. This co-methylation relationship study represents a new area of study for both RA and PD and provides new ideas for further study of the shared biological mechanisms of RA and PD.
32104275 Anti-CCL22 increases regulatory T cells in CD4(+) T cells of rheumatoid arthritis patients 2020 Mar Abnormality in the number and function of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) in peripheral blood has been linked to the initiation and progression of rheumatoid arthritis (RA). Effect of chemokine CCL22 on the number of Tregs in CD4(+) T cells and the underlying mechanism were investigated. Downregulation of peripheral Tregs were observed while upregulation of serum chemokine CCL22 in RA patients. Tregs count and the expression of FOXP3 (Tregs function-related maker) and phosphorylated-signal transducer and activator of transcription 5 (p-STAT5) in CD4(+) T cells from RA patients were increased while C-C chemokine receptor 4 (CCR4) was decreased by anti-CCL22 antibody, however, recombinant CCL22 resulted in the opposite effects in CD4(+) T cells from the healthy control. STAT5 inhibitor significantly reversed the effects of anti-CCL22 antibody. Similarly, sinomenine, an anti-arthritis drug, which decreased CCL22 and CCR4, showed the same trends as the above events, and was reversed by recombinant CCL22 or STAT5 inhibitor. Collectively, anti-CCL22 induced the number of Tregs via STAT5 pathway, leading to expansion of Tregs and subsequently to control of the autoimmune reaction in RA patients. Our study provides s novel strategy for RA treatment.
32743509 Autoantibodies against citrullinated serum albumin in patients with rheumatoid arthritis. 2019 Dec Rheumatoid arthritis (RA) is a chronic, potentially debilitating, inflammatory disease that primarily affects synovial joints. While the etiology of RA remains incompletely understood, it is clear that the disease is autoimmune in nature. A hallmark of RA is that the specific epitopes on self-antigens that are targeted by the immune system are often modified by arginine deimination, also referred to as citrullination. In fact, anti-citrullinated protein autoantibodies (ACPA) at high enough titers are diagnostic of RA and appear to have many different targets. Here, we report that RA patients have IgG autoantibodies that react with human serum albumin (HSA) when it had been citrullinated by protein arginine deiminase (PAD) 4, but not by PAD2. Unmodified albumin was not recognized by autoantibodies. In a cohort of 79 RA patients, 38% had anti-citrullinated HSA (anti-cit-HSA) reactivity above the cut-off of the average plus two standard deviations in a healthy subject cohort (n = 16). The titers of these autoantibodies correlated with ACPA status and seropositivity. There was also a trend toward correlation with the presence of radiographic joint erosions, but this did not reach statistical significance. Finally, patients with anti-cit-HSA were more frequently treated with biologics and combination regimens than patients without these autoantibodies. We conclude that ACPA directed against citrullinated albumin exist in a subset of RA patients. Because of the abundance of albumin, its modification by citrullination, as well as autoantibodies binding to it, may have deleterious consequences for the health of affected RA patients.
32010301 miR-155 promotes fibroblast-like synoviocyte proliferation and inflammatory cytokine secre 2020 Feb The present study aimed to explore the expression and effects of microRNA (miR)-155 in synovial fibroblasts of patients with rheumatoid arthritis (RA). A total of 89 synovial tissues from RA patients and 49 control synovial tissues were collected, and the levels of miR-155 were measured by reverse transcription quantitative-PCR and western blotting. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues from the control group and were used to evaluate the roles of miR-155 and forkhead box protein O3a (FOXO3a). MTT assay was used to measure the proliferation of FLS. The expression of miR-155 in RA synovial tissues was significantly higher than that in the control group, but the expression of FOXO3a was significantly lower. In RA synovial tissues, miR-155 expression was negatively correlated with FOXO3a expression, but was positively correlated with the release of inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). A dual-luciferase reporter system showed that miR-155 inhibited the expression of FOXO3a in FLS cells. miR-155 also promoted secretion of the inflammatory cytokines IL-1β, IL-6 and TNF-α by FLS and proliferation of these cells by targeting FOXO3a.
31448362 Acute corneal perforation 1 week following uncomplicated cataract surgery: the implication 2019 Jan Dry eye disease is a common ocular surface disease in patients who are undergoing cataract surgery. The significance of dry eye disease is often underestimated or overlooked during preoperative assessment of cataract. We report an 80-year-old patient, with a background of seropositive rheumatoid arthritis and diabetes, who presented with an acute corneal melt and perforation associated with undiagnosed dry eye disease and use of topical ketorolac 1 week following an uncomplicated cataract surgery. The patient underwent repeated corneal gluing for corneal perforation and was subsequently diagnosed and treated for bilateral moderate-severe dry eye disease. This case highlights the importance of meticulous preoperative assessment and management of the ocular surface, especially in patients with systemic diseases such as rheumatoid arthritis and diabetes prior to cataract surgery. The implication of the use of topical nonsteroidal anti-inflammatory drugs following cataract surgery - which might have contributed to the process of corneal melt in our case - is also discussed.
31185701 The Potential Role of Genomic Medicine in the Therapeutic Management of Rheumatoid Arthrit 2019 Jun 10 During the last decade, important advances have occurred regarding understanding of the pathogenesis and treatment of rheumatoid arthritis (RA). Nevertheless, response to treatment is not universal, and choosing among different therapies is currently based on a trial and error approach. The specific patient's genetic background influences the response to therapy for many drugs: In this sense, genomic studies on RA have produced promising insights that could help us find an effective therapy for each patient. On the other hand, despite the great knowledge generated regarding the genetics of RA, most of the investigations performed to date have focused on identifying common variants associated with RA, which cannot explain the complete heritability of the disease. In this regard, rare variants could also contribute to this missing heritability as well as act as biomarkers that help in choosing the right therapy. In the present article, different aspects of genetics in the pathogenesis and treatment of RA are reviewed, from large-scale genomic studies to specific rare variant analyses. We also discuss the shared genetic architecture existing among autoimmune diseases and its implications for RA therapy, such as drug repositioning.
30899276 Computational Molecular Phenotypic Analysis of PTPN22 (W620R), IL6R (D358A), and TYK2 (P11 2019 Rheumatoid arthritis (RA) is a chronic autoimmune disorder of bone joints caused by the complex interplay between several factors like body physiology, the environment with genetic background. The recent meta-analysis of GWAS has expanded the total number of RA-associated loci to more than 100, out of which approximately ∼97% (98 variants) loci are located in non-coding regions, and the other ∼3% (3 variants) are in three different non-HLA genes, i.e., TYK2 (Prp1104Ala), IL6R (Asp358Ala), and PTPN22 (Trp620Arg). However, whether these variants prompt changes in the protein phenotype with regards to its stability, structure, and interaction with other molecules, remains unknown. Thus, we selected the three clinically pathogenic variants described above, as positive controls and applied diverse computational methods to scrutinize if those mutations cause changes in the protein phenotype. Both wild type and mutant protein structures of PTPN22 (W620R), IL6R (D358A), and TYK2 (P1104A) were modeled and studied for structural deviations. Furthermore, we have also studied the secondary structure characteristics, solvent accessibility and stability, and the molecular interaction deformities caused by the amino acid substitutions. We observed that simple nucleotide predictions of SIFT, PolyPhen, CADD and FATHMM yields mixed findings in screening the RA-missense variants which showed a ≥P-value threshold of 5 × 10(-8) in genome wide association studies. However, structure-based analysis confirms that mutant structures shows subtle but significant changes at their core regions, but their functional domains seems to lose wild type like functional interaction. Our findings suggest that the multidirectional computational analysis of clinically potential RA-mutations could act as a primary screening step before undertaking functional biology assays.
30641795 Hypertriglyceridaemic waist is associated with hyperuricaemia and metabolic syndrome in rh 2019 Jan BACKGROUND: /Aim: The hypertriglyceridaemic waist (HTGW) phenotype has been described and suggested in general population as a cardiovascular risk marker. The aim of the present study was to evaluate the HTGW phenotype as a marker related to HUC and MetS in rheumatoid arthritis (RA). MATERIALS AND METHODS: This was a cross-sectional study was designed in 250 RA Mexicans patients. The HTGW phenotype was defined as elevated waist circumference and elevated triglyceride concentration. Logistic regression analysis was used to evaluate the association between the HTGW phenotype, HUC and MetS in its traditional NCEP/ATPIII versions and modified (HTGWm and MetSm). RESULTS: The prevalence of HTGW and HTGWm it was 20.4% and 32%, respectively. All patients with HTGW presented MetS (P < 0.001), and in a multivariate model, the HTGW phenotype was the marker most closely related to HUC in comparison to components of MetS. CONCLUSION: The HTGW may represent a marker for screening of cardiometabolic risk in RA patients, so in clinical practice can be implemented as a low-cost marker in the evaluation of the patient regardless of clinical characteristics of disease.
32185348 Vitamin D Deficiency and Rheumatoid Arthritis: Epidemiological, Immunological, Clinical an 2019 Jun BACKGROUND/AIM: Vitamin D displays an immunologic effect which can modulate function of Th17-related cytokines and thereby prevent perpetuation of inflammation in chronic disorders like rheumatoid arthritis (RA). This review aims to conduct a literature review to provide a summary of recent studies addressing the relationship between vitamin D deficiency and RA based on epidemiological, immunological and therapeutic aspects. METHODS: PubMed, Scopus and Google scholar were searched for relevant papers published between 2000-2018. RESULTS: Low intake of vitamin D increases the risk of incident RA, and vitamin D deficiency has been shown to be inversely associated with RA activity in most of these studies. However, characteristics of RA and serum vitamin D status differ across the studies. The results of studies on the effect of supplemental vitamin D in RA vary, from no efficacy to significant improvement in disease activity, as well as quality of life. This should be attributed to variations in dosage of vitamin D, duration of treatment, baseline serum vitamin D in RA patients and characteristics of RA across diverse studies. CONCLUSION: Current data indicate a therapeutic potential for vitamin D in RA. However, further studies are needed to identify an optimal and effective dosage, duration of treatment and patients who will get the best benefit from the treatment.
32051709 Is pentraxin 3 level an effective biomarker in disease activity in patients with rheumatoi 2020 INTRODUCTION: The aim of the current study was to identify whether serum pentraxin 3 (PTX3) level could be a marker of increased inflammation in rheumatoid arthritis (RA) patients. MATERIAL AND METHODS: The study included 41 patients diagnosed with RA according to the American College of Rheumatology (ACR) 1990 diagnostic criteria. We compared the serum PTX3 levels between RA patients and a healthy control group, the relationship between PTX3 level and disease activity was also examined. RESULTS: A statistically significant difference was determined between the RA patients and controls as regards PTX3, platelets, C-reactive protein, and mean platelet volume results (p = 0.042, p = 0.007, p = 0.017, p < 0.001, respectively). There was no statistically significant difference in terms of PTX3 level between anti-CCP-positive and -negative patients (p = 0.368). No statistically significant difference was determined in respect of PTX3 levels between RA patients with different disease activity scores (p = 0.346). CONCLUSIONS: No relationship was determined between PTX3 and disease activity in RA patients, nor with traditional clinical and biochemical measurements of disease activity. However, the PTX3 levels of the RA patients were found to be high in comparison with the control group. Because, from these results, the role of PTX3 in the pathogenesis of RA cannot be ignored, there is a need for further studies to determine the potential role of PTX3 in RA pathogenesis.
31993436 Use of Animal and Animal Products for Rheumatoid Arthritis Treatment: An Explorative Study 2019 Severe fatigue, pain, deformity, and disability, are the major concerns for rheumatoid arthritis (RA). The extreme pain experienced by the patients often force them to experiment with various indigenous substances including animals and animal products. However, there is little evidence on the use of animals or animal products as traditional medicine in RA. Hence, this study was aimed to explore the experience and perception of patients toward the use of animals and animal products for the treatment of RA. A qualitative, explorative study was conducted at the out-patient-department of Rheumatology of a tertiary care medical college and hospital at Cuttack, Odisha, India. Out of 113 patients with RA, 18 patients gave history of use of animal and/or animal products and were selected for in-depth interviews. The content analysis methods were used for data analysis. Four major categories emerged: (1) prevailing patterns of traditional treatment of RA using animals, (2) beliefs and values behind the traditional treatment of RA, (3) sources and traditional learning pathway of indigenous practices on RA, and (4) ethical aspects of the indigenous practice of using animals and/or animal products in the treatment of RA. This study revealed the practice of eating dead animals to get relief from RA. However, there was hardly any perceived positive outcome of the practice; which indicates the lack of awareness of rational, scientific, treatment, and prevalence of irrational and unethical practices for the treatment of RA. Hence, community awareness, social mobilization, and newer screening tools are necessary to improve the timely detection and prevention of irrational treatment practices among RA patients.
31934007 Inhibition of the TGF-β/Smads signaling pathway attenuates pulmonary fibrosis and induces 2019 We explored whether transforming growth factor (TGF-β)/Smads signaling pathway influences rheumatoid arthritis (RA)-associated pulmonary fibrosis (PF) and proliferation of RA synovial fibroblast (RA-SF). Expression levels of TGF-β1 in RA + PF patients, RA patients and healthy controls were determined. Rat models of RA were successfully induced and assigned into groups. The mRNA, phosphorylation and protein expressions of TGF-β1, Smad2 and Smad3 were detected. The serum expressions of inflammatory factors were measured by ELISA. Tissue sections were observed using hematoxylin-eosin (HE) and Masson staining. The SF cells were separated and grouped. Cell viability and migration were determined. The highest expressions of TGF-β1 were found in RA + PF patients, followed by RA patients and then healthy controls. RA + PF rats were characterized by less activity, worse appetite, messy and less shining hair, thin sloppy stool and increased joint swelling. Compared with the normal group, the expressions of TGF-β1, Smad2, Smad3, IL-6 and TNF-α were elevated in the RA + PF group. Meanwhile, the swelling and pulmonary fibrosis of lung tissues was worse, the lung capacity and serum level of IL-10 were decreased. However, SB431542 can reverse the above results. The cell activity and cell migration ability of cells in the RA + PF + SB431542 group were inhibited compared to those in the blank group. Based on above findings, the inhibition of the TGF-β/Smads signaling pathway alleviates the pulmonary fibrosis in rats with RA and suppresses cell viability and migration of synovial fibroblasts.
31118961 A Network Pharmacology Study on the Active Ingredients and Potential Targets of Tripterygi 2019 Traditional Chinese medicine has specific effect on some chronic diseases in clinic, especially in rheumatic diseases. Tripterygium wilfordii Hook (TWH) is a traditional Chinese medicine commonly used in the treatment of rheumatoid arthritis (RA); the unique therapeutic effect has been confirmed by a large number of research papers. TWH has many compounds that lead to its active compounds. However, the potential targets and pharmacological and molecular mechanism of its action treatment of rheumatic diseases are not entirely clear. Therefore, the network pharmacology approach is needed to further study and explore its treatment mechanism. We have successfully set up 10 networks, including four major networks and other networks. Four major networks include rheumatoid arthritis disease network, compound-compound target network of TWH, TWH compound target-rheumatoid arthritis disease network, and TWH-rheumatoid arthritis disease-mechanism network. Other networks consist of RA disease and TWH related targets clusters, biological processes, and pathways network. Our study successfully predicted, explained, and confirmed the TWH of RA disease molecular synergy and found the potential of RA related targets, cluster, biological process, and pathways. This study not only provides prompts to the researcher who explores pharmacological and biological molecular mechanism of TWH applying to RA disease, but also proves a feasible method for discovering potential activated compounds from Chinese herbs.
31090044 Immunogenicity of Sarilumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Ina 2019 Sep INTRODUCTION: This open-label study evaluated the immunogenicity, safety, and efficacy of sarilumab monotherapy in patients with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response or intolerance to prior conventional synthetic disease-modifying antirheumatic drugs. METHODS: Adults with RA (n = 132) were randomized to receive subcutaneous sarilumab (150 [n = 65] or 200 mg [n = 67]) every 2 weeks (q2w) for 24 weeks. Endpoints included incidence of antidrug antibodies (ADAs) at week 24, safety, and efficacy. RESULTS: Persistent ADAs occurred in eight patients (12.3%) receiving sarilumab 150 mg q2w, seven of whom (10.8%) had neutralizing antibodies (NAbs), and in four patients (6.1%) receiving sarilumab 200 mg q2w, two of whom (3.0%) had NAbs; all exhibited low antibody titers. Infections and neutropenia were the most common adverse events (AEs). There were three serious AEs, no reports of anaphylaxis, and few hypersensitivity reactions (e.g., rash) with no notable differences in hypersensitivity reactions in ADA-positive patients relative to ADA-negative patients. Changes in absolute neutrophil count, alanine aminotransferase level, and platelet count were consistent with interleukin-6 signaling blockade and in agreement with previous observations. At week 24, overall American College of Rheumatology 20%/50%/70% improvement criteria responses were 73.8%/53.8%/29.2%, respectively, with sarilumab 150 mg q2w and 71.6%/50.7%/29.9% with sarilumab 200 mg q2w. No patients with an ADA-positive response showed loss of efficacy. CONCLUSIONS: ADA titers were low and persistent ADAs and NAbs occurred relatively infrequently in both sarilumab dose groups. ADA did not meaningfully impact the safety or efficacy of either dose of sarilumab over 24 weeks. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02121210. FUNDING: Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Plain language summary available for this article.