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ID PMID Title PublicationDate abstract
31665501 Viral antigens elicit augmented immune responses in primary Sjögren's syndrome. 2020 Jul 1 OBJECTIVES: Infections have been suggested in the pathogenesis of primary SS (pSS). Systematic studies of immune responses to microbial antigens in vivo may be performed during vaccination. In the present study, we therefore longitudinally followed patients with pSS and controls during split-virion influenza vaccination to identify pSS-specific cellular, transcriptomic and serological responses. METHODS: Patients without treatment (pSSUntr, n = 17), on hydroxychloroquine-treatment (pSSHCQ, n = 8), and healthy controls (n = 16) were included. Antibody titres were determined by ELISA. Plasma proteins were measured by proximity extension assay. Monocyte gene expression was assessed by Nanostring. Routine laboratory tests were performed and clinical disease symptoms were registered by questionnaires. RESULTS: pSSUntr developed higher vaccine-specific IgG titres compared with controls. Notably, anti-Ro52 autoantibody titres increased in pSSUntr but remained unchanged in pSSHCQ. No changes in disease symptoms including EULAR Sjögren's Syndrome Patient Reported Index score were registered. Twenty-four hours after vaccination, the leucocyte count in pSSUntr decreased, with a concomitant increase of CCL7 in plasma. Transcriptomic analysis in monocytes revealed differential vaccination-related expression of the NEMO/IKBKG gene, and its higher induced expression in pSSUntr associated with higher serological vaccine responses. Moreover, titres of vaccine-specific antibodies were associated with higher vaccination-induced NF-κB signalling and higher steady-state IFN signatures in monocytes, and with the levels of several plasma proteins with soluble PD-1 displaying the strongest association. CONCLUSION: We observed augmented innate and adaptive immune responses in pSS following viral antigen exposure suggesting an underlying hyper-responsiveness to immune challenges, supporting a role for infections driving the immunopathology and acting as environmental risk factor for pSS.
32066939 Publisher Correction: Immunological adaptations in pregnancy that modulate rheumatoid arth 2020 Mar An amendment to this paper has been published and can be accessed via a link at the top of the paper.
32340695 Pathogenesis of Axial Spondyloarthritis - Sources and Current State of Knowledge. 2020 May Scientific breakthroughs have culminated in the development of the spondyloarthritis (SpA) concept as a family of rheumatic diseases, distinct from rheumatoid arthritis. The demonstration of inflammatory lesions in the sacroiliac joints and spine of patients with axial symptoms of SpA who lacked radiographic features of ankylosing spondylitis (AS) helped refine the SpA concept. Axial SpA includes patients with AS and patients with axial symptoms previously categorized as undifferentiated SpA. This review examines the sources of knowledge that inform axial SpA pathogenesis, highlighting current limitations, and a basic working model of axial SpA pathogenesis.
33334795 Vascular Endothelial Growth Factor-A Is Associated with Platelets and Complement 4 in Pati 2020 Nov OBJECTIVE: We aimed at investigating the expression level of vascular endothelial growth factor-A (VEGF-A) in patients with primary Sjögren's Syndrome (pSS) and evaluating the relationship between serum VEGF-A and the laboratory indicators that are associated with it in pSS. METHODS: The VEGF-A levels were measured by ELISA in a total of 88 participants, including 58 patients with pSS and 30 healthy people. The VEGF-A levels between two groups were analyzed. RESULTS: The serum levels of VEGF-A in pSS and control groups were 175.50 (112.00,296.50) pg/mL and 181.50 (155.25,288.50) pg/mL, without statistically significant difference. The associations were found between serum levels of VEGF-A with C reactive protein (CRP) (r=0.265, P<0.05), white blood cells (WBC) (r=0.302, P<0.05), neutrophils (NEUT) (r=0.349, P<0.05), platelets(PLT) (r=0.276, P<0.05), complement 3 (C3) (r=0.477, P<0.05), complement 4 (C4) (r=0.387, P<0.05) and CA19-9 (r=0.392, P<0.05). Among these laboratory indicators, VEGF-A was correlated with platelets and complement 4 in patients with pSS. CONCLUSIONS: In patients with pSS, the levels of VEGF-A were independently influenced by the levels of platelet and complement 4, which indicated the intermodulation between the growth factor and immune system in the autoimmune disease.
32649686 Importance of tear volume for positivity of tear matrix metalloproteinase-9 immunoassay. 2020 The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.
32250392 Circular RNA sequencing indicates circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers of 2020 Sep 1 OBJECTIVES: This study aims to characterize the expression profiles of circRNAs in primary Sjogren's Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS. METHODS: We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS. RESULTS: Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes. CONCLUSION: This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS.
33298650 [Primary diffuse large B-cell lymphoma of the breast in a male patient with Sjögren's syn 2020 When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.
32918388 Male patients with primary Sjögren's syndrome: A distinct clinical subgroup? 2020 Oct AIM: Because the clinical and immunologic phenotypes of male primary Sjögren's syndrome (pSS) patients have not been fully elucidated, we aimed to investigate the clinical characteristics of male patients with pSS in Korea. METHODS: We retrospectively evaluated the medical records of male patients with pSS, who visited Seoul St. Mary's Hospital, a tertiary referral center in Korea, between January, 2015 and December, 2019. Of a total of 1107 patients with pSS, 33 were male, which is a prevalence of 2.9%. These 33 were compared with 353 female patients as a control group, whose records were extracted from the database of the Korean Initiative of Primary Sjögren's Syndrome, our nationwide pSS database. Various clinical aspects were assessed, including secretory functions, extra-glandular manifestations (EGM), disease activity-measuring indices, and hematological and serological variables. RESULTS: Male patients were less likely to complain of xerophthalmia and xerostomia and presented with fewer patient-reported disease outcomes and glandular dysfunctions as compared with female patients. White blood cell and neutrophil counts and the seropositivity of anti-ribonucleoprotein antibody were higher in male patients than in their female counterparts, whereas anti-Ro/SSA antibody and rheumatoid factor were less concentrated in sera from male patients. Pulmonary involvement and lymphoma were seen more frequently in male patients. Among other EGMs, female patients had a higher prevalence of autoimmune thyroid diseases. CONCLUSIONS: Male patients with pSS present less severe glandular dysfunctions, better patient-reported disease outcomes, and a higher prevalence of pulmonary involvement and lymphoma compared to females, suggesting distinct clinical phenotypes of pSS.
31308202 Outcome Monitoring and Clinical Decision Support in Polyarticular Juvenile Idiopathic Arth 2020 Feb OBJECTIVE: Inconsistent assessment and treatment may impair juvenile idiopathic arthritis (JIA) outcomes. We aimed to improve polyarticular JIA (rheumatoid factor-positive and -negative) outcomes by standardizing point-of-care disease activity monitoring and implementing clinical decision support (CDS) to reduce treatment variation. METHODS: We performed a quality improvement initiative in an outpatient pediatric rheumatology practice. The interventions, implemented from April to November 2016, included standardized disease activity measurement, disease activity target review, and phased introduction of polyarticular JIA CDS to guide medication selection, dosing, treatment duration, and tapering. Process measures included visit-level target attestation (goal: 50%) and CDS use (goal: 15%). Our goal was to reduce the polyarticular JIA clinical Juvenile Arthritis Disease Activity Score (cJADAS-10) by at least 10%. Included patients had at least 2 visits from April 2016 through July 2017, and were classified as having early (≤ 6 mos) or established disease (> 6 mos). RESULTS: Patients with polyarticular JIA (n = 97; 81% established disease) were observed for 10.3 months (interquartile range: 6.4-12.3). Target attestation and CDS use occurred in a mean of 77% and 45% of polyarticular JIA visits, respectively. The median cJADAS-10 decreased significantly in both early (16.5 to 2.7, p < 0.001) and established polyarticular JIA (2.1 to 1.0, p = 0.01). A high proportion of patients with early disease received biologic therapy (73.7%). In established disease, although prescription of nonbiologic and biologic disease-modifying antirheumatic drugs remained similar overall, adalimumab prescribing increased (12.8% to 23.1%, p = 0.008). CONCLUSION: Implementation of structured disease activity monitoring and CDS in polyarticular JIA was associated with significant reductions in disease activity scores in both early and established disease.
31944344 Inflammasomes contributing to inflammation in arthritis. 2020 Mar Inflammasomes are intracellular multiprotein signaling platforms that initiate inflammatory responses in response to pathogens and cellular damage. Active inflammasomes induce the enzymatic activity of caspase-1, resulting in the induction of inflammatory cell death, pyroptosis, and the maturation and secretion of inflammatory cytokines IL-1β and IL-18. Inflammasomes are activated in many inflammatory diseases, including autoinflammatory disorders and arthritis, and inflammasome-specific therapies are under development for the treatment of inflammatory conditions. In this review, we outline the different inflammasome platforms and recent findings contributing to our knowledge about inflammasome biology in health and disease. In particular, we discuss the role of the inflammasome in the pathogenesis of arthritic diseases, including rheumatoid arthritis, gout, ankylosing spondylitis, and juvenile idiopathic arthritis, and the potential of newly developed therapies that specifically target the inflammasome or its products for the treatment of inflammatory diseases.
32455138 Higher Serum CCN3 Is Associated with Disease Activity and Inflammatory Markers in Rheumato 2020 Nephroblastoma overexpressed protein (NOV/CCN3), the early discovered member of the CCN family, has recently been suggested to be involved in a number of inflammatory processes, including wound healing, alveolar epithelial cell inflammation, cancer metastasis, and macrophage foam cell formation. However, the role of CCN3 in rheumatoid arthritis (RA), a classic autoimmune and inflammatory disease, remains elusive. RA is a chronic systemic autoimmune disease that eventually leads to cartilage and bone destruction and joint dysfunction. In this study, we investigated the potential of serum CCN3 as a biomarker for RA. The serum levels of CCN3 were measured by ELISA. The clinical and laboratory parameters were collected from a clinical record system, and disease activity was determined by joint disease activity score 28 (DAS28). Our results showed that the serum levels of CCN3 were significantly increased in RA patients compared to healthy controls. Furthermore, the CCN3 level was positively correlated with DAS28 (CRP), DAS28 (ESR), and the level of anti-CCP Ab, an autoantibody highly specific for RA. Furthermore, CCN3 showed a positive correlation with inflammatory cytokine IL-6, while no significant correlation with TNF-α was observed. These data suggest that CCN3 plays an important role in the development of RA and might be a potential disease activity biomarker for RA.
32840050 Patients' perceptions on shared decision making during prescription of subcutaneous biolog 2020 Dec OBJECTIVES: The aim of this study was to explore the preferences of patients with rheumatic diseases and their perceived experience regarding participation in shared decision making (SDM) when they were prescribed a subcutaneous (SC) biological drug. METHODS: A printed survey was handed to 1,000 patients with inflammatory rheumatic diseases treated with SC biological drug. The survey included closed questions about preferences regarding decision making and about patients' experience when they were prescribed an SC biological drug. Descriptive statistics were performed with stratification by patient profiles, using chi-square for comparisons between groups. RESULTS: A total of 592 surveys were received (response rate 59.2%, mean age 51.7 years, 57.6% women). Some 28.2% of patients reported preferring to take part in treatment selection, a percentage that was higher in younger patients, in those with higher academic degree and in those who search information in sources different to that of health care professionals. Over half of patients (56.3%) perceived that the rheumatologist considered their opinion when prescribing an SC biological drug, a percentage higher in younger people. Only in 40.8% of cases did the patients' preference match their perception of their participation in the process. No differences were observed by sex, disease or number of biologics. CONCLUSIONS: Patients with inflammatory rheumatic diseases want information about their treatments but mostly leave the prescription decision to the rheumatologist. Younger people, or those with higher academic degree, more often want to participate in the SDM. There are discrepancies between patient preferences and perceptions of this process.
33519474 Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in 2020 Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.
33204424 Proteomic analysis of extracellular vesicles reveals an immunogenic cargo in rheumatoid ar 2020 OBJECTIVES: Extracellular vesicles (EVs) from rheumatoid arthritis (RA) synovial fluid (SF) have been reported to stimulate the release of pro-inflammatory mediators from recipient cells. We recently developed a size exclusion chromatography (SEC)-based method for EV isolation capable of high-quality enrichments from human SF. Here, we employed this method to accurately characterise the SF EV proteome and investigate potential contributions to inflammatory pathways in RA. METHODS: Using our SEC-based approach, SF EVs were purified from the joints of RA patients classified as having high-level (n = 7) or low-level inflammation (n = 5), and from osteoarthritis (OA) patients (n = 5). Protein profiles were characterised by mass spectrometry. Potential contributions of EV proteins to pathological pathways and differences in protein expression between disease groups were investigated. RESULTS: Synovial fluid EVs were present at higher concentrations in RA joints with high-level inflammation (P-value = 0.004) but were smaller in diameter (P-value = 0.03) than in low-level inflammation. In total, 1058 SF EV proteins were identified by mass spectrometry analysis. Neutrophil and fibroblast markers were overrepresented in all disease groups. Numerous proteins with potential to modulate inflammatory and immunological processes were detected, including nine citrullinated peptides. Forty-five and 135 EV-associated proteins were significantly elevated in RA joints with high-level inflammation than in RA joints with low-level inflammation and OA joints, respectively. Gene ontology analysis revealed significant enrichment for proteins associated with 'neutrophil degranulation' within SF EVs from RA joints with high-level inflammation. CONCLUSION: Our results provide new information about SF EVs and insight into how EVs might contribute to the perpetuation of RA.
32968710 Long-term effectiveness and safety of infliximab, golimumab and golimumab-IV in rheumatoid 2020 BACKGROUND: Long-term clinical registries are essential tools to evaluate new therapies in a patient population that differs from those in randomized clinical trials. The objectives are to describe the profile of rheumatoid arthritis (RA) patients treated with anti-TNF agents in Canadian routine care. METHODS: RA patients eligible for treatment with Infliximab (IFX), golimumab (GLM) or intravenous golimumab (GLM-IV) as per their respective Canadian product monographs were enrolled into the BioTRAC registry between 2002 and 2017. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in disease activity. Safety was evaluated by the incidence of adverse events (AEs) and drug survival. RESULTS: Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females ranged from 77.0-86.6%, the mean ages from 55.8-57.7 and the mean disease duration from 6.5-8.6 years. A significant decrease in baseline disease duration and disease activity parameters (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) was observed over time. Treatment with IFX, GLM- and GLM-IV significantly improved all disease parameters over time. The incidence of AEs was 105, 113 and 82.6 /100 PYs and the incidence of SAEs was 11.7, 11.2 and 4.68 /100 PYs for IFX, GLM- and GLM-IV-treated patients, respectively. CONCLUSION: Differences in baseline characteristics between patients treated with an anti-TNFs over time shows the evolution of treatment modalities over time. All treatments significantly reduced disease activity and improved functionality in a similar fashion. The incidence of adverse events was consistent with the safety profiles of IFX and GLM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00741793 (Retrospectively registered on August 26, 2008).
32955447 Feasibility of Self-Monitoring Rheumatoid Arthritis With a Smartphone App: Results of Two 2020 Sep 21 BACKGROUND: Several mobile apps that monitor symptoms of rheumatoid arthritis (RA) exist, but a recent systematic review indicated that high-quality apps are lacking. When patients self-monitor their own disease with patient-reported outcomes (PROs) and self-initiate care at the right moment, it may be possible to reduce the frequency of their clinic visits, which would reduce health care burden and costs. We developed an app, that is, the MijnReuma Reade app, for this purpose and performed 2 pilot tests with weekly self-monitoring. OBJECTIVE: The primary objective of this study was to design, develop, and evaluate the usability, satisfaction, and usage of the MijnReuma Reade app-an app that allows patients with RA to monitor their own disease. The secondary objective was to review the patients' perspectives on app usage and its intended purpose. METHODS: This app was designed in collaboration with patients with RA, rheumatologists, and information technology experts. Two 1-month pilot studies were performed, after which satisfaction (0-10 scale), usability (system usability scale, 0-100), and usage (proportion of completed questionnaires) of this app were assessed. After the second pilot study, semistructured interviews were performed to determine patients' perspectives and the promoters and barriers of app usage. RESULTS: In the first and second pilot study, 42 and 27 patients were included, respectively. Overall, the patients were satisfied (medians, 8 and 7) and found the app usable (mean system usability scores, 76 and 71) in pilot studies 1 and 2, respectively. App usage declined over time in both the pilot studies; 61% (17/28) and 37% (10/27) of the patients who disclosed their usage statistics completed the final weekly questionnaire in pilot study 1 and pilot study 2, respectively. Approximately 81% (25/31) of the patients indicated they would like to skip hospital visits if the self-monitored disease activity is low. In the semistructured interviews, technical problems, internal resistance (respondent fatigue, the app reminded them of their disease), and a lack of symptoms were identified as barriers for usage. Patients reported that "experiencing more grip on their disease" and "improved communication with their physician" were promoters for usage. Patients reported that pain positively mediated usage, that is, more pain promoted and less pain discouraged app usage. CONCLUSIONS: This study illustrates the feasibility of the MijnReuma Reade app that enables self-monitoring of the disease activity in patients with RA with the overarching aim to allocate clinical consultations according to need. Satisfaction with the app and usability of the app were found to be high; however, app usage declined over time. Patients acknowledged the potential of the app to self-monitor their own disease and would like to be able to skip clinic visits if the monitored disease activity is low. To evaluate this strategy, a randomized controlled trial is underway.
32130182 A Smartphone App for Self-Monitoring of Rheumatoid Arthritis Disease Activity to Assist Pa 2020 Feb 19 BACKGROUND: Telemedicine based on self-measurement of disease activity could be one of the key components to create the health care system of the future. Previous publications in various medical fields have shown that it is possible to safely telemonitor patients while reducing the number of outpatient clinic visits. For this purpose, we developed a mobile phone app for patients with rheumatoid arthritis (RA), which allows them to self-monitor their disease. OBJECTIVE: The objective of this study is to assess the safety and efficacy of self-initiated care assisted by a smartphone app in patients with RA. METHODS: This is a randomized controlled trial that will be performed for 1 year. A total of 176 patients with RA will be randomized to either self-initiated care with only one scheduled follow-up consultation assisted by our app or usual care. The coprimary outcome measures are the number of outpatient clinic consultations with a rheumatologist taking place during the trial period and the mean disease activity score as measured by the disease activity score 28 (DAS28) at 12 months. The secondary outcomes are patient satisfaction, adherence, patient empowerment, and cost evaluation of health care assisted by the app. RESULTS: Recruitment started in May 2019, and up to 18 months will be required for completion of recruitment. Thus far, 78 patients have been randomized, and thus far, experiences with the app have been positive. The study results are expected to be published by the end of 2021. CONCLUSIONS: The completion of this study will provide important data regarding the following: (1) safety of self-initiated care supported by a smartphone app in terms of DAS28 and (2) efficacy of lowering health care usage with this new strategy of providing health care. TRIAL REGISTRATION: Netherlands Trial Register NL7715; https://www.trialregister.nl/trial/7715. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15105.
33010198 Higher Checkpoint Inhibitor Arthritis Disease Activity may be Associated With Cancer Progr 2020 Oct OBJECTIVE: To describe clinical features associated with cancer outcomes of patients with immune checkpoint inhibitor (ICI)-associated arthritis. METHODS: Observational study of patients with ICI-arthritis enrolled in a single-center registry. Arthritis phenotype and activity, medications, and cancer status were recorded at every visit. We used descriptive statistic, and Kaplan-Meier curves using two-sided log-rank test and Cox regression analysis were used to identify factors associated with cancer progression-free survival (PFS). RESULTS: Forty-two patients with ICI-arthritis were followed for a median (interquartile range [IQR]) of 7.4 (1.7, 14.7) months. Fifty-seven percent were female, 33% had melanoma, and 69% received anti-programmed death ligand 1 monotherapy. Median time from ICI initiation to arthritis onset was 2.8 (0.8, 11.2) months. Sixty-two percent had a rheumatoid arthritis (RA)-like small-joint presentation; 27% of all patients were rheumatoid factor and/or cyclic citrullinated peptide positive. Median (IQR) Clinical Disease Activity Index (CDAI) on presentation was 15 (8, 24); 62% required systemic glucocorticoids, 55% required disease-modifying antirheumatic drugs (DMARDs), and 69% had ongoing arthritis at 6 months. Arthritis led to ICI discontinuation in five patients. In univariate analysis, baseline CDAI, DMARD use, earlier arthritis onset, and longer duration of follow-up were associated with shorter PFS. In multivariable Cox regression analysis controlling for DMARD use and time to arthritis onset, CDAI was a significant predictor of cancer progression (hazard ratio 1.09, 95% confidence interval [CI] 1.00-1.19, P = 0.05) CONCLUSION: ICI-arthritis most commonly presents with an RA-like phenotype. High disease activity, as measured by CDAI, may portend cancer progression.
33396851 Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic 2020 Dec 30 BACKGROUND: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. RESULTS: The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. CONCLUSIONS: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.
31469249 Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability t 2020 Jan OBJECTIVE: To evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. METHODS: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively. RESULTS: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). CONCLUSION: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.