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ID PMID Title PublicationDate abstract
34101570 Long-term safety and efficacy of olokizumab in patients with rheumatoid arthritis and inad 2021 Jul OBJECTIVE: This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an anti-interleukin (IL)-6 monoclonal antibody, in patients with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor-alpha inhibitors. METHODS: Eligible patients completed study RA0056, which tested several doses of OKZ, placebo (PBO), and tocilizumab (TCZ) plus methotrexate (MTX) in Western countries, and RA0083 included several doses of OKZ and PBO plus MTX in Asian countries. Both studies were followed by open-label extension (OLE) studies with OKZ 120 mg every 2 weeks, RA0057 and RA0089, respectively. Safety assessments were reported up to 124 weeks in RA0057 and 92 weeks in RA0089. Efficacy assessments were reported up to week 60 in RA0057 and week 52 in RA0089. No formal statistical hypothesis testing was performed, and missing data were not imputed. RESULTS: A total of 190 patients in RA0057 and 103 patients in RA0089 received OKZ with median treatment duration of 14.1 and 10.1 months, respectively. Serious adverse events (SAEs) were reported in 44 patients (23.2%, 32.7 events per 100 patient-years [PY]) in RA0057 and in 13 patients (12.6%, 23.6 events per 100 PY) in RA0089. Among treatment-emergent adverse events (TEAEs), including SAEs, infections were the most common events. TEAEs leading to withdrawal were reported in 33 (17.4%) patients in RA0057 and in 7 (6.8%) patients in RA0089. Disease activity score 28-joint count on the basis of C-reactive protein level, clinical disease activity index, and simplified disease activity index, as well as the American College of Rheumatology 20%, 50%, and 70% response rates were maintained during the OLE studies, including in those who switched from PBO or TCZ. Improvements in patient-reported outcomes were maintained in OLEs as well. CONCLUSION: In the 2 long-term studies, OKZ treatment demonstrated a safety profile expected for IL-6 blocking agents without new safety signals and led to sustained improvements in RA symptoms, physical function, and quality of life.
34055402 Interleukin-18 in Brazilian Rheumatoid Arthritis Patients: Can Leflunomide Reduce It? 2021 OBJECTIVES: Rheumatoid arthritis affects about 1% of the world's population. This is a chronic autoimmune disease. It is predominant in females with progressive joint damage. Immune cells are involved, especially Th1/Th17 lymphocytes and their inflammatory cytokines. These proteins have different functions in the immune system, such as IL-16 is a chemotactic factor; IL-18 can activate NFκB transcription producing inflammatory proteins; IL-31 can activate the JAK/STAT pathway which leads to the production of inflammatory factors in chronic diseases; IL-33 promotes IL-16 secretion which causes lymphocyte recruitment, and IL-32 and IL-34 appear to increase TNF secretion by macrophages activation in AR. The aim of this study was to evaluate serum levels of IL-16, IL-18, IL-31, IL-32, IL-33, and IL-34 and compare them with the severity and treatment of RA patients if there are any correlations. METHODS: A total of 140 RA patients and 40 healthy donors were recruited from the Department of Rheumatology at Hospital das Clínicas from the Federal University of Pernambuco. 60 AR patients were naïve for any treatment. Serum cytokine levels were determined using an ELISA kit. RESULTS: Serum IL-16 (p = 0.0491), IL-18 (p < 0.0001), IL-31 (p = 0.0004), and IL-32 (p = 0.0040) levels were significantly increased in RA patients compared with healthy donors. It was observed that patients using leflunomide had the lowest IL-18 levels, close to controls levels (p = 0.0064). CONCLUSION: IL-16, IL-18, IL-31, and IL-32 are increased in the serum of RA patients. IL-18 is at lower levels in those AR who are taking leflunomide as treatment.
33896676 Assessment of Atypical Cardiovascular Risk Factors Using Single Photon Emission Computed T 2021 Aug BACKGROUND: Ischemic heart disease (IHD) is a health care problem in women that increases morbimortality, particularly in developing countries. There is limited information regarding atypical risk factors associated with IHD in Mexican women. AIM: To explore risk factors in women that could contribute to IHD and myocardial dysfunction using the single photon emission computed tomography (SPECT) myocardial perfusion study (MPS). METHODS: We designed a cross-sectional study in which we evaluated atypical and typical risk factors using a clinical questionnaire. We performed a SPECT-MPS to evaluate the presence of ischemia/infarction, decreased left ventricular ejection fraction, systolic dyssynchrony and diastolic function by peak filling rate and time to peak filling rate. RESULTS: 172 women were included, 64 with IHD. Adverse events during pregnancy (premature birth and miscarriage), rheumatoid arthritis, gynecological conditions (menopause and age of first menstruation) and low educational level, together with previously known typical risk factors were associated with infarction or ischemia and ventricular dysfunction. Potential associated factors for systolic dyssynchrony were rheumatoid arthritis (OR: 2.90, 95% CI: 0.95-8.66, p = 0.054) and history of premature birth (OR: 0.13, 95% CI: 0.01-0.66, p <0.01). Although those women with arterial hypertension and smoking shown an increased risk for dyssynchrony, these factors were not statistically significant. Low-educational level (OR 2.16, 95% CI 1.1-4.18, p = 0.019) was associated with decreased peak filling rate. CONCLUSION: The presence of atypical risk factors in women could lead to decreased myocardial function, particularly in women at risk of developing IHD.
33856739 Gout, Rheumatoid Arthritis, and the Risk of Death Related to Coronavirus Disease 2019: An 2021 May OBJECTIVES: The objectives for this study were to assess whether gout and/or rheumatoid arthritis (RA) are risk factors for coronavirus disease 2019 (COVID-19) diagnosis and to assess whether gout and/or RA are risk factors for death from COVID-19. METHODS: We used data from the UK Biobank. Multivariable-adjusted logistic regression was employed in the following analyses: analysis A, to test for association between gout and/or RA and COVID-19 diagnosis (n = 473,139); analysis B, to test for association between gout and/or RA and death from COVID-19 in a case-control cohort of people who died of or survived COVID-19 (n = 2059); analysis C, to test for association between gout and/or RA and death from COVID-19 in the entire UK Biobank cohort (n = 473,139). RESULTS: RA, but not gout, was associated with COVID-19 diagnosis in analysis A. Neither RA nor gout was associated with risk of death in the group diagnosed with COVID-19 in analysis B. However, RA was associated with risk of death related to COVID-19 by using the UK Biobank cohort in analysis C, independent of comorbidities and other measured risk factors (odds ratio [OR] 1.9; 95% confidence interval CI 1.2-3.0). Gout was not associated with death related to COVID-19 in the same UK Biobank analysis (OR 1.2; 95% CI 0.8-1.7). CONCLUSION: RA is a risk factor for death from COVID-19 by using the UK Biobank cohort. These findings require replication in larger data sets that also allow for inclusion of a wider range of factors.
32645129 Multiple extremity necrosis in fatal calciphylaxis: Case report. 2021 Apr INTRODUCTION: The clinical impact of vascular calcification is well established in the context of cardiovascular morbidity and mortality, but other clinical syndromes, such as calciphylaxis, although less frequent, have a significant impact on chronic kidney disease. METHODS: Case report of a 27-year-old woman, who had complained of bilateral pain in her toes for 3 days, with the presence of small necrotic areas in the referred sites. She had a history of type 1 diabetes (25 years ago), with chronic kidney disease, on peritoneal dialysis, in addition to rheumatoid arthritis. She was admitted to the hospital, which preceded the current condition, due to exacerbation of rheumatoid arthritis, evolving with intracardiac thrombus due to venous catheter complications, when she started using warfarin. Ischemia progressed to her feet, causing the need for bilateral amputations. Her chirodactyls were also affected. Thrombophilia, vasculitis, endocarditis or other embolic sources were investigated and discarded. Her pathology report evidenced skin necrosis and superficial soft parts with recent arterial thrombosis, and Monckeberg's medial calcification. We started treatment with bisphosphonate and sodium thiosulfate, conversion to hemodialysis and replacement of warfarin with unfractionated heparin. Despite all the therapy, the patient died after four months of evolution. DISCUSSION: Calciphylaxis is a rare microvasculature calcification syndrome that results in severe ischemic injuries. It has pathogenesis related to the mineral and bone disorder of chronic kidney disease combined with the imbalance between promoters and inhibitors of vascular calcification, with particular importance to vitamin K antagonism. CONCLUSION: The preventive strategy is fundamental, since the therapy is complex with poorly validated effectiveness.
33452004 Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monother 2021 Jan 15 OBJECTIVES: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. METHODS: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. RESULTS: The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments. CONCLUSIONS: FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.
34962093 Evaluation of an Intervention to Support Patient-Rheumatologist Conversations About Escala 2022 Apr OBJECTIVE: This study's objective was to test whether an online video intervention discussing appropriate treatment escalation improves willingness to change treatment in people living with rheumatoid arthritis (RA). METHODS: We conducted a controlled, randomized trial among patients with RA enrolled in ArthritisPower, a United States patient registry. We recruited participants by email and surveyed their assessment of disease activity (patient global), satisfaction with disease control (patient acceptable symptom state), attitudes about RA medications, decisional conflict (decisional conflict scale), and willingness to modify RA treatment (choice predisposition scale, higher scores are better) if or when recommended by their rheumatologist. Intervention groups watched educational videos relevant to a treat-to-target (T2T) strategy, whereas control groups viewed vaccination-related videos as an "attention control." We compared the between-group difference in patients' willingness to modify RA treatment (primary outcome) and difference in decisional conflict about changing RA treatment (secondary outcome) after watching the videos using t tests. RESULTS: Participants with self-reported RA (n = 208) were 90% White and 90% women, with a mean (standard deviation) age of 50 (11) years, and 52% reported familiarity with the RA T2T strategy. We found a significant improvement in between-group difference in willingness to change RA treatment among intervention versus control participants (0.49 [95% confidence interval 0.09-0.88], P = 0.02). The effect size (Glass's delta) for the intervention was 0.48. Decisional conflict about treatment change decreased, but the between-group difference was not significant. CONCLUSION: This novel educational patient-directed intervention discussing appropriate treatment escalation was associated with improved willingness to change RA treatment if or when recommended by a rheumatologist. Further studies should evaluate whether this change in patients' predisposition translates into actual treatment escalation.
34511031 Favorable clinical response and drug retention of anti-IL-6 receptor inhibitor in rheumato 2021 Sep 13 OBJECTIVE: Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level. METHOD: RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation. RESULTS: A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP(1), 0-0.3; CRP(2), 0.3-1.8; CRP(3), 1.8-18.4 mg/dL). In CRP(3), the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP(1)-CRP(3). CONCLUSION: IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.
34159494 Use of ultrasound to diagnose and monitor interstitial lung disease in rheumatic diseases. 2021 Sep Interstitial lung disease (ILD) is one of the most relevant extra-articular manifestations of rheumatic diseases resulting in a substantial increase in morbidity and mortality. Early diagnosis and close monitoring to identify patients at high risk of progression are crucial to establish the need for targeted treatment with immunomodulatory and antifibrotic drugs, with potential ability to change the course of the disease. However, there are unmet needs in this field as pulmonary auscultation, chest radiography, or pulmonary function studies do not allow identification of the most incipient stages of the disease. High-resolution computed tomography (HRCT), which is the current gold standard for diagnosis and evolutionary control, is problematic owing to ionizing radiation, cost, and accessibility. In this context, lung ultrasound (LUS) is an attractive tool in a growing research and validation process. The identification of vertical artifacts, such as B lines, and alterations of the pleural line present a good correlation with the presence of ILD by HRCT and have a good concordance with the extent and severity of the disease, with sensitivity and negative predictive values of up to 100%. Regarding the monitoring of the evolution, the validation process of LUS is in a more preliminary phase but data is encouraging. All this, together with its safety, accessibility, low cost, and good patient acceptance, postulate LUS as a useful tool for the screening of ILD and for the optimization of the indications of HRCT. Key Points • The good sensitivity and negative predictive values of LUS postulate this technique as a useful tool for the screening of ILD and for the optimization of the indications of HRCT in rheumatic diseases.
34159450 Hearing impairment and diverse health outcomes : An umbrella review of meta-analyses of ob 2021 Oct BACKGROUND: Globally, it is estimated that approximately 1.3 billion people live with some form of hearing impairment. Major causes of hearing loss include infection/disease, age-related factors, and occupational factors. Numerous systematic reviews and meta-analyses have attempted to synthesise literature on these topics. To date there has not been a systematic evaluation of the relationships between hearing impairment and diverse physical, mental, and social outcomes. OBJECTIVE: We performed an umbrella review of systematic reviews of observational studies with meta-analyses for any physical disease, biomarkers of disease, mental health or cognitive outcomes, and/or modifiable risk factors associated with hearing impairment. METHODS: For each meta-analytic association, random effects summary effect size, 95% confidence intervals, heterogeneity, evidence for small-study effect, excess significance bias and 95% prediction intervals were calculated, and risk of bias was assessed via the AMSTAR2 tool. These were used to grade significant evidence (p < 0.05) from I to IV, using the recommendations from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From 3747 studies, 21 were included covering 54 outcomes. Overall, 44/54 outcomes (82%) yielded significant results. Of the highest quality evidence, age-related hearing loss and non-specific hearing impairment were negatively associated with several types of cognitive impairments; pediatric bilateral hearing loss was negatively associated with quality of life, sensorineural hearing loss was positively associated with rheumatoid arthritis and tinnitus was positively associated with temporomandibular disorders. CONCLUSION AND RELEVANCE: Results show moderate quality evidence for associations between several types of hearing impairments and cognitive difficulties, quality of life and systemic diseases such as rheumatoid arthritis. Practitioners and public health policies should note these findings when developing relevant healthcare policies.
34047099 [Chemical constituents from Morinda citrifolia and their inhibitory activities on prolifer 2021 May The chemical constituents from the stems and leaves of Morinda citrifolia were isolated and purified by column chromatography methods with silica gel, ODS, Sephadex LH-20 and preparative high performance liquid chromatography(HPLC). The structures of the isolated compounds were identified by physicochemical properties and spectroscopic analysis, as well as comparisons with the data reported in literature. 17 compounds were isolated from the 90% ethanol extract of the stems and leaves of M. citrifolia, and were identified as 9,10-dihydroxy-4, 7-megastigmadien-3-one(1), 5,12-epoxy-6,9-hydroxy-7-megastigmen-3-one(2), fukinone(3), β-eudesmol(4), sarmentol F(5), 4, 5-dihydroblumenol A(6), 3-hydroxy-β-ionone(7), aristol-8-en-1-one(8), ergosta-7-en-3β-ol(9), ergosta-7-ene-3β,5α,6β-triol(10),(22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol(11), olivil(12), 4-epi-larreatricin(13), chushizisin Ⅰ(14), rabdosia acid A(15), glycerol monolinoleate(16) and(9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-trienoate(17). All compounds were isolated from M. citrifolia for the first time. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their inhibitory activities on the proliferation of synoviocytes in vitro using MTS met-hod. Compounds 1-11 showed significant anti-rheumatoid arthritis activities, displaying the inhibitory effects on the proliferation of MH7 A synovial fibroblast cell with the IC_(50) values ranging from(38.69±0.86) to(203.45±1.03) μmol·L~(-1).
33570260 Postapproval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Anti 2021 Mar OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. METHODS: IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. RESULTS: For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. CONCLUSION: In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.
34949700 Fine particles matter components and interstitial lung disease in rheumatoid arthritis. 2021 Dec 23 Exposure to ambient fine particulate matter (PM(2.5)) is a risk factor for pulmonary and systemic autoimmune diseases, however evidence on which PM(2.5) chemical components are more harmful is still scant. Our goal is to investigate potential associations between PM(2.5) components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA).New-onset RA subjects identified from a United States health care insurance database (MarketScan) were followed for new onset of RA associated ILD (RA-ILD) from 2011 to 2018. Annual ambient PM(2.5) concentrations of its chemical components (i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust, and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to one year before ILD onset or end of study were assigned to subjects based on their metropolitan division or core-based statistical area codes. A novel time-to-event quantile-based g(generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM(2.5) chemical components adjusting for age, sex, and prior chronic obstructive pulmonary disease (as a proxy for smoking).We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% confidence interval 1.47-1.63) per every decile increase in all seven exposures. Ammonium, mineral dust, and black carbon contributed more to ILD risk than the other PM(2.5) components.In conclusion, exposure to elements of PM(2.5), particularly ammonium, increases ILD risk in RA.
34724982 Epidemiology of musculoskeletal symptoms, rheumatologic disorders, and disability in the Z 2021 Nov 2 BACKGROUND: The purpose of this study was to determine the prevalence of musculoskeletal complaints, rheumatologic diseases, and disability among the Zoroastrian population in Iran. METHODS: The city of Yazd, in central Iran was selected for this study, with the highest population of Zoroastrians in Iran. Subjects were selected by cluster sampling of 9 neighborhoods populated with Zoroastrians. Subjects ≥15 years old were interviewed by trained interviewers in their houses. The validated Farsi translation of Community Oriented Program for the Control of Rheumatic Disease (COPCORD) Core Questionnaire (CCQ) was used for this study. Subjects with musculoskeletal complaints (pain, stiffness and/or swelling) were examined by a rheumatologist. Laboratory tests and radiographic exams were performed when deemed necessary. RESULTS: Two-thousand subjects were interviewed during a 12-month period, of which 956 were male, and 1044 were female. The mean age was 41.1 ± 18.3 years (95%CI: 40.3-41.9). 36.9% of the subjects had university-level education. In the 7 days prior to the interview, 27.6% of the subjects had musculoskeletal complaints, with the knee, dorsolumbar spine, and shoulder being the most common sites of complaints. The most common rheumatologic diagnoses were osteoarthritis (21.5%) and low back pain (10.3%). Rheumatoid arthritis was diagnosed in 1.2% of the subjects. CONCLUSIONS: The epidemiology of musculoskeletal complaints and rheumatologic disorders was inconsistent with previous COPCORD studies in Iran, with a lower prevalence of musculoskeletal complaints in general, lower rates of Behçet and lupus, and a higher prevalence of rheumatoid arthritis. The findings of this study can be for development of better prevention, screening, and treatment programs for the vulnerable population of Zoroastrians in Iran.
34273260 Impaired Antibody Response to the BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine 2021 Sep OBJECTIVE: With a vaccine effectiveness of 95% for preventing coronavirus disease 2019 (COVID-19), Pfizer-BioNTech BNT162b2 (BNT162b2) was the first vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to be approved. However, immunosuppressive therapy was an exclusion criterion in the phase 3 trial that led to approval. Thus, extrapolation of the trial results to patients with rheumatic diseases treated with immunosuppressive drugs warrants caution. METHODS: Patients with systemic lupus erythematosus (SLE; n = 61) and rheumatoid arthritis (RA; n = 73) were included from the COPANARD (Corona Pandemic Autoimmune Rheumatic Disease) cohort, followed since the beginning of the COVID-19 pandemic. Patients received the BNT162b2 vaccine between December 2020 and April 2021. All patients had total antibodies against SARS-CoV-2 measured before vaccination and 1 week after the second vaccination (VITROS Immunodiagnostic Products). RESULTS: Of 134 patients (median age, 70 years), 77% were able to mount a detectable serological response to the vaccine. Among patients treated with rituximab, only 24% had detectable anti-SARS-CoV-2 antibodies in their serum after vaccination. The time since the last rituximab treatment did not seem to influence the vaccine response. No significant difference was observed between patients with RA or SLE when adjusting for treatment, and no correlation between antibody levels and age was detected (r = -0.12; P = 0.18). CONCLUSION: Antibody measurements against SARS-CoV-2 in patients with RA and SLE after two doses of the BNT162b2 vaccine demonstrated that 23% of patients could not mount a detectable serological response to the vaccine. B cell-depleting therapy (BCDT) is of specific concern, and our findings call for particular attention to the patients receiving BCDT.
34085777 Inorganic Dust Exposure During Military Service as a Predictor of Rheumatoid Arthritis and 2021 Jul OBJECTIVE: Rheumatoid arthritis (RA) and other autoimmune (AI) conditions are associated with inorganic dust exposure. Many military activities are likely to entail inorganic dust exposures. We wished to identify associations between prior military dust exposure and RA and other AI conditions. METHODS: We studied persons from a roster of Army, Navy, Air Force, or Marine Corps personnel who had served in Operation Enduring Freedom and Operations Iraqi Freedom and New Dawn. We linked military occupational codes to a job exposure matrix assigning dust exposure likelihood. We used the Veterans Affairs Health Care System (VAHCS) electronic health care records to identify cases of RA, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), vasculitis, and inflammatory myositis. Generalized estimating equations modeled risk of RA and other AI conditions associated with dust exposure, taking into account military service branch, age at first VAHCS encounter, sex, race/ethnicity, smoking status, and years of military service. RESULTS: Of 438 086 veterans (68% ever-smokers), 44% were classified with likely or somewhat likely dust exposure. Cases included 1139 cases with RA, 467 cases with SLE, and 180 cases with other AI diseases (SSc, vasculitis, or inflammatory myositis). Military dust exposure was associated with increased odds of RA (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.003-1.20) and increased odds of SSc, vasculitis, or inflammatory myositis (OR = 1.23; 95% CI = 1.14-1.34) but was protective for SLE (OR = 0.81; 95% CI = 0.76-0.88). CONCLUSION: Dust exposure during past military service comprises an occupational and environmental risk factor for RA and other AI diseases. This is potentially relevant for prevention activities.
33943043 Foot and Ankle Problems in Patients With Rheumatoid Arthritis in 2019: Still an Important 2021 Jun OBJECTIVE: To study the prevalence of foot pain in patients with rheumatoid arthritis (RA) and whether including a 12-joint foot count in addition to the 28-joint count (from the Disease Activity Score 28 [DAS28]) improved detection of foot or ankle pain. In addition, the association between the self-reported foot and ankle score (SEFAS), patient-reported function, and disease-specific factors was studied. METHODS: Physician-reported data (swollen/tender 12-joint foot count, DAS28, and medication) and patient-reported data (foot/ankle pain, physical function, global health, and SEFAS) were assessed during a clinical visit. Data were analyzed with t test, χ(2) tests, and regression analysis. RESULTS: A total of 320 patients with RA were included (mean age 63 years, SD 13 years; 73% women), of whom 69% reported foot or ankle pain. Patients who reported foot or ankle pain had a lower mean age and worse disease activity, general pain, function, and global health (P ≤ 0.016), and fewer were in remission (50% versus 75%; P < 0.001) compared with patients without foot pain. The 12-joint foot count identified 3.2% and 9.5% additional patients with swollen and tender joints, respectively, compared with the 28-joint count. The SEFAS was associated with walking problems (β = -2.733; 95% confidence interval [CI] = -3.963 to -1.503) and worse function (β = -3.634; 95% CI = -5.681 to -1.587) but not with joint inflammation severity. CONCLUSION: The prevalence of foot or ankle pain in patients with RA is high. The 12-joint foot count had minor effects on detecting patients with foot pain. However, the SEFAS contributed additional information on foot problems that was not identified by joint examinations alone.
33389312 Mobile health technologies for the management of rheumatic diseases: a systematic review o 2021 Jul Rheumatic diseases are serious conditions with a low uptake of conservative treatments. Mobile health (mHealth) applications (apps) offer potential to assist the self-management of rheumatic diseases. Our goal was to perform a systematic review of available mHealth apps for rheumatic diseases in Brazil. We focused on the most prevalent rheumatic diseases: osteoarthritis, rheumatoid arthritis, fibromyalgia, systemic lupus erythematosus, osteoporosis, and axial spondylarthritis. Google Play Store and AppStore in Brazil were queried by two independent reviewers on September 2020, and the quality of eligible mHealth apps was assessed using the Mobile App Rating Scale (MARS). Of the 3173 mHealth apps found, five were eligible for inclusion. Two for fibromyalgia and two for axial spondylarthritis offered exercise, educational content, and tools to track patient-reported symptoms; and one for osteoporosis offered educational content and tracking tools only. The included apps scored moderately on the MARS quality scale, with a mean score (SD) of 3.1 (0.7) on a 0-5 scale. Most apps scored poorly based on credibility, user interface and experience, and engagement. There is growing interest in the development of mHealth technologies to support rheumatic diseases patients. Although the majority of the included apps came from non-profit organizations, they are still of poor quality and limited functionality. This study is a call for to the development of new user-centered mHealth apps that can empower rheumatic diseases patients in Brazil, especially in the area of osteoarthritis, rheumatoid arthritis, and lupus, since no apps were found.
32459610 Effect of the Intramolecular Hydrogen Bond on the Active Metabolite Analogs of Leflunomide 2021 BACKGROUND: Leflunomide (LFM) and its active metabolite, teriflunomide (TFM), have drawn a lot of attention for their anticancer activities, treatment of rheumatoid arthritis and malaria due to their capability to inhibit dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. In this investigation, the strength of intramolecular hydrogen bond (IHB) in five analogs of TFM (ATFM) was analyzed employing density functional theory (DFT) using B3LYP/6-311++G (d, p) level and molecular orbital analysis in the gas phase and water solution. A detailed electronic structure study was performed using the quantum theory of atoms in molecules (QTAIM) and the hydrogen bond energies (EHB) of stable conformer obtained in the range of 76-97 kJ/mol, as a medium hydrogen bond. The effect of substitution on the IHB nature was studied by natural bond orbital analysis (NBO). (1)H NMR calculations showed an upward trend in the proton chemical shift of the enolic proton in the chelated ring (14.5 to 15.7ppm) by increasing the IHB strength. All the calculations confirmed the strongest IHB in 5-F-ATFM and the weakest IHB in 2-FATFM. Molecular orbital analysis, including the HOMO-LUMO gap and chemical hardness, was performed to compare the reactivity of inhibitors. Finally, molecular docking analysis was carried out to identify the potency of inhibition of these compounds against PfDHODH enzyme. TFM acts as an inhibitor of dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. Leflunomide and its active metabolite teriflunomide have been identified as drugs for treatment of some diseases, such as multiple sclerosis (MS), rheumatoid arthritis (RA), malaria, and cancer. Hydrogen bonds play a key role in the interaction between drugs and enzymes. OBJECTIVES: The aim of the present work is to investigate the effect of the strength of intramolecular hydrogen bonds (IHBs) in the active metabolite analogs of leflunomide or analogs of teriflunomide (ATFMs) and study the interaction of these inhibitors against the PfDHODH enzyme using quantum mechanical methods. METHODS: At first, intramolecular hydrogen bonds in five ATFMs were evaluated by the DFT method, quantum theory of atoms in molecules (QTAIM), nuclear magnetic resonance (NMR), natural bond orbital (NBO), and molecular orbital (MO) analyses. Then, the interaction of these inhibitors against the PfDHODH enzyme were compared using molecular docking study. RESULTS: All the computed results confirm the following trend in the intramolecular hydrogen bond strength in five mono-halo-substituted 2-cyano-3-hydroxy-N-phenylbut-2-enamide (ATFM): 5-FATFM> 4-Br-ATFM ≈ 3-Br-ATFM>3-Cl-ATFM>TFM-Z>2-F-ATFM which is in agreement with QTAIM, NMR, and NBO results. Docking results show that 5-F-ATFM (E(HB)=97kJ/mol) has the minimum MolDock score due to its considerable IHB strength. CONCLUSION: For strong IHBs (E(HB)>100kJ/mol), C=O and O-H group are involved in the intramolecular interactions and do not contribute to the external interactions. Also, the docking study revealed maximum binding energy between TFM-Z and PfDHODH enzyme.
34370060 Intra-articular use of radium dichloride ([(223)Ra] RaCl(2)) showed relevant anti-inflamma 2021 Dec Rheumatoid arthritis (RA) is an inflammatory chronic autoimmune disease. The treatment of RA is difficult and, in many cases, ineffective, and the arsenal of drugs is limited. Due the longevity of the disease, RA may cause extreme musculoskeletal disorders with a high impact on quality of life. Also, RA is related with severe comorbidities decreasing the life expectancy. Finally, RA has been reported to impact in economy and healthy public. In this direction, the necessity to discover new strategies to efficiently treat RA is immediate. In this direction, we have reported the use of low doses of [(223)Ra] RaCl(2) (radium dichloride) as intra-articular injection to treat RA. Mice were post-treated with [(223)Ra] RaCl(2) (1.48 µCi; i.a.) 24 h after zymosan stimulus. Zymosan-induced arthrithis is responsible for leucocyte recruitment (total leukocytes, neutrophils, and mononuclear cells), which were inhibited by intra-articular injection of [223Ra] RaCl2 (69%, 77%, and 66%, respectively).