Effects Of Rheumatoid Arthritis Research Articles

Revealing the impact of autophagy-related genes in rheumatoid arthritis: Insights from bioinformatics

BackgroundRheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. MethodsIn this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. ResultsThe results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. ConclusionThis study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

Concomitant Sjögren’s disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort

ObjectiveTo investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren’s disease (SjD).MethodsIn this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders.ResultsWe identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07–1.6]; OMA HR 1.12 [0.91–1.37]; JAKi HR 0.97 [0.62–1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46–0.84]) and JAKi (HR 0.52 [0.28–0.96]).ConclusionRA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.

The effect of Rheumatoid Arthritis on Eye Health

The effect of Rheumatoid Arthritis on Eye Health

Forsythiaside A exhibits anti-migration and anti-inflammation effects in rheumatoid arthritis invitro model.

Rheumatoid arthritis (RA) is a kind of systemic autoimmune disease, and the joint inflammation and cartilage destruction are the major features. Some traditional Chinese medicine have been discovered to exhibit regulatory roles in the treatment of RA. Forsythiaside A (FA) as an active ingredient isolated from forsythia suspensa has been discovered to participate into the regulation of some diseases through improving inflammation. However, the regulatory effects of FA on the progression of RA keep indistinct. IL-1β treatment (10 ng/mL) in MH7A cells was built to mimic RA invitro (cell) model. The cell viability was examined through CCK-8 assay. The cell proliferation was detected through Edu assay. The levels of TNF-α, IL-6, and IL-8 were evaluated through ELISA. The protein expressions were measured through western blot. The cell apoptosis was assessed through flow cytometry. The cell migration and invasion abilities were tested through Transwell assay. In this study, it was revealed that the cell proliferation was strengthened after IL-1β treatment (p < .001), but this effect was reversed after FA treatment in a dose-increasing manner (p < .05). Furthermore, FA suppressed inflammation in IL-1β-triggered MH7A cells through attenuating the levels of TNF-α, IL-6, and IL-8 (p < .05). The cell apoptosis was lessened after IL-1β treatment (p < .001), but this effect was rescued after FA treatment (p < .05). Besides, the cell migration and invasion abilities were both increased after IL-1β treatment (p < .001), but these changes were offset after FA treatment (p < .05). Eventually, FA retarded the JAK/STAT pathway through reducing p-JAK/JAK and p-STAT/STAT levels (p < .01). Our study manifested that FA exhibited anti-migration and anti-inflammation effects in RA invitro model (IL-1β-triggered MH7A cells) through regulating the JAK/STAT pathway. This work hinted that FA can be an effective drug for RA treatment.

The association of milk products with rheumatoid arthritis: A cross-sectional study from NHANES

ObjectiveMilk products are a major part of the western diet, but the role of their effect in rheumatoid arthritis (RA) is controversial. The objective of this study was to explore the relationship between milk products and RA in the United States (US) population. MethodsIn the cross-sectional study, a total of 12,813 participants aged 20years or older were selected from the National Health and Nutrition Examination Survey (NHANES). Consumption of milk products was collected by personal interview, and RA status was obtained by self-reported questionnaires. The association between milk products and RA was estimated by using the weighted logistic regression model. ResultsWe found a negative association of once a day or more milk products intake with self-reported RA prevalence (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.53 to 0.86; P<0.001). A linear trend between consumption of milk products and the prevalence of RA (P<0.01) was also observed. In subgroup analysis, protective effects of milk products on RA were more pronounced in several groups (i.e., Mexican Americans, highly educated and drinking individuals, etc.). However, no interaction effect of stratification variables and the frequency of milk products intake with RA was detected. After imputing missing data, the sensitivity analysis showed the same association. ConclusionThis study suggested a negative association between consumption of milk products and RA among US population. Further investigations are warranted to validate the causal association and the underlying mechanism.

Dysregulation of B lymphocyte development in the SKG mouse model of rheumatoid arthritis.

Rheumatoid arthritis is a chronic and systemic inflammatory disease that affects approximately 1% of the world's population and is characterised by joint inflammation, the destruction of articular cartilage and bone, and many potentially life-threatening extraarticular manifestations. B lymphocytes play a central role in the pathology of rheumatoid arthritis as the precursors of autoantibody secreting plasma cells, as highly potent antigen-presenting cells, and as a source of various inflammatory cytokines, however, the effects of rheumatoid arthritis on B lymphocyte development remain poorly understood. Here, we analyse B lymphocyte development in murine models of rheumatoid arthritis, quantifying all the subsets of B cell precursors in the bone marrow and splenic B cells using flow cytometry. We demonstrate a severe reduction in pre-B cells and immature B cells in the bone marrow of mice with active disease, despite no major effects on the mature naïve B cell numbers. The loss of B cell precursors in the bone marrow of the affected mice was associated with a highly significant reduction in the proportion of Ki67+ cells, indicating impaired cell proliferation, while the viability of the B cell precursors was not significantly affected. We also observed some mobilisation of the B cell precursor cells into the mouse spleen, demonstrated with flow cytometry and pre-B colony forming units assays. In summary, the current work demonstrates a severe dysregulation in B lymphocyte development in murine rheumatoid arthritis, with possible implications for B cell repertoire formation, tolerance induction, and disease mechanisms.

Effects of Rheumatoid Arthritis on the Progression of Pulpitis and Apical Periodontitis in SKG Mice

IntroductionRheumatoid arthritis (RA) is an autoimmune disease that involves joint inflammation. Although periodontal disease reportedly contributes to RA onset, the associations of RA with pulpitis and apical periodontitis have not been described. The purpose of this study was to examine the effects of immune response disruption of RA for pulpitis and apical periodontitis with SKG mice. MethodsSKG and BALB/c (control) mice were used to establish models of pulp infection. Histologic studies of pulp and apical periodontal tissue were performed at 3, 5, 7, 14, and 28 days; odontoblast dynamics were analyzed by antinestin staining, and apoptotic cells were examined by TdT-mediated digoxygenin (biotin)-dUTP nick end labeling staining. ResultsInflammatory cell infiltration into the exposed pulp was observed at 3 days in the SKG and control group groups; the infiltration extended to the apical pulp area at 14 days after surgery. Inflammatory cell infiltration and bone resorption in the apical pulp area were observed from 14–28 days in the SKG and control groups; there were significant increases in inflammatory cell infiltration and bone resorption in the control group at 28 days. The numbers of apoptotic cells in pulp and apical periodontal tissue were higher in the SKG group than in the control group at 14 and 28 days. The number of odontoblasts decreased in the SKG and control groups until 14 days and then disappeared in the SKG and control groups at 28 days. ConclusionsThis study suggested that immune response disruption in RA is involved in prolonging the inflammatory state of pulpitis and apical periodontitis.

Beyond Seasoning-The Role of Herbs and Spices in Rheumatic Diseases.

Although we have witnessed remarkable progress in understanding the biological mechanisms that lead to the development of rheumatic diseases (RDs), remission is still not achieved in a substantial proportion of patients with the available pharmacological treatment. As a consequence, patients are increasingly looking for complementary adjuvant therapies, including dietary interventions. Herbs and spices have a long historical use, across various cultures worldwide, for both culinary and medicinal purposes. The interest in herbs and spices, beyond their seasoning properties, has dramatically grown in many immune-mediated diseases, including in RDs. Increasing evidence highlights their richness in bioactive molecules, such as sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, as well as their antioxidant, anti-inflammatory, antitumorigenic, and anticarcinogenic properties. Cinnamon, garlic, ginger, turmeric, and saffron are the most popular spices used in RDs and will be explored throughout this manuscript. With this paper, we intend to provide an updated review of the mechanisms whereby herbs and spices may be of interest in RDs, including through gut microbiota modulation, as well as summarize human studies investigating their effects in Rheumatoid Arthritis, Osteoarthritis, and Fibromyalgia.

Moringa Oleifera Extract Decreases Interleukin 6 Levels and Disease Activity in Rheumatoid Arthritis Patients

Moringa oleifera (MO) has anti-inflammatory, anti-arthritis, and immunosuppressant effects in Rheumatoid Arthritis (RA). This study aims to determine the effect of moringa oleifera extract on interleukin 6 levels and disease activity in RA. This research, with 30 patients, was divided into two groups: the intervention and the placebo. The intervention group received 40.50 mg/kg BW/day of Moringa oleifera extract for one month. IL-6 levels and SDAI scores were measured before and after the treatment. Paired t-test showed that IL-6 levels (p=0.070) and SDAI Scores (p=0.142) before and after MO administration for the control group were not significantly different (p&gt; 0.05). Paired t-test IL-6 (p=0.001) and SDAI Scores (p=0.001) before and after giving MO to the treatment group decreased significantly (p &lt;0.05). Independent t-test shows that the two changes, Delta-IL6 (p=0,008) and Delta-SDAI (p=0,017), are significantly different (p&lt;0.05). Moringa Oleifera Extract decreases IL-6 Levels and SDAI Scores in RA Patients. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 416-421

Effect of rheumatoid arthritis on primary total knee arthroplasty and revision arthroplasty

The demand for total knee arthroplasty (TKA) is rapidly increasing worldwide. The most common indication for TKA is osteoarthritis (OA); however, some patients with rheumatoid arthritis (RA) also undergo TKA. This study aimed to investigate the effects of RA on TKA. Our findings revealed that patients with RA underwent TKA at a younger age than did patients with OA. However, contrary to the findings of pre-21st century studies, the average age of TKA among patients with RA was not significantly different from that of patients with OA. Additionally, patients with RA had a 1.5-fold higher risk of undergoing TKA. Although not statistically significant, patients with RA had a higher revision TKA rate, a shorter time until revision TKA, and underwent more revision TKAs due to infections than did patients with OA. An analysis of factors that affect revision TKA revealed that the risk of revision increased if the erythrocyte sedimentation rate and C-reactive protein levels were increased at the time of TKA. This study showed that patients with RA have a slightly higher risk of undergoing TKA than did patients with OA. Furthermore, the presence of inflammation at the time of TKA increases the risk of revision; therefore, inflammation should be adequately controlled before performing TKA.

Moringa Oleifera Extract Decreases Interleukin 6 Levels and Disease Activity in Rheumatoid Arthritis Patients

Moringa oleifera (MO) has anti-inflammatory, anti-arthritis, and immunosuppressant effects in Rheumatoid Arthritis (RA). This study aims to determine the effect of moringa oleifera extract on interleukin 6 levels and disease activity in RA. This research, with 30 patients, was divided into two groups: the intervention and the placebo. The intervention group received 40.50 mg/kg BW/day of Moringa oleifera extract for one month. IL-6 levels and SDAI scores were measured before and after the treatment. Paired t-test showed that IL-6 levels (p=0.070) and SDAI Scores (p=0.142) before and after MO administration for the control group were not significantly different (p&gt; 0.05). Paired t-test IL-6 (p=0.001) and SDAI Scores (p=0.001) before and after giving MO to the treatment group decreased significantly (p &lt;0.05). Independent t-test shows that the two changes, Delta-IL6 (p=0,008) and Delta-SDAI (p=0,017), are significantly different (p&lt;0.05). Moringa Oleifera Extract decreases IL-6 Levels and SDAI Scores in RA PatientsInternational Journal of Human and Health Sciences Vol. 07 No. 02 April’23 Page: 122-127

Rheumatoid Arthritis Effects on Kidney and Liver and their Correlations with CDAI

Rheumatoid arthritis (RA) is a disease characterized by chronic autoimmune inflammation of body joints, causing movement disability, loss of functions, joint damage, and many complications. Persistent usage of anti-rheumatic drugs has several side effects, which may cause heart, kidney, or liver diseases. This study aims to assess the influence of RA duration on kidney and liver enzymes and study the correlation between these enzyme levels and RA disease activity (CDAI). This study collected a total of 150 blood samples. 100 samples for RA patients (61 were seropositive, 39 were seronegative), and 50 for healthy Control. throughout the period from November 2021 to February 2022. The blood samples were collected from Baghdad Teaching Hospital / Rheumatology Consulting Clinic. General information had been collected from each subject according to a questionnaire that had been applied for this purpose.  The age groups of patients and control were between 22-72 years, and 26-62 years old, respectively. The female participants were more than the male counterparts. The blood samples were taken from patients and control groups to screen liver and kidney functions by an automated biochemical system using the SELECTRA PRO X2 device, in addition to the ESR test. The study showed that the levels of urea, creatinine, GPT, and GOT were either normal or slightly elevated and they are non-significantly associated with RA disease activity, the little effect of RA on kidney and liver may be related to the low doses of methotrexate and corticosteroid therapy which used mostly for these patients and didn’t reach to toxicity.

The effect of rheumatoid arthritis on upper extremity functions: A kinematic perspective.

To examine the global upper extremity kinematics in 3D while performing "jar opening motion" in Rheumatoid Arthritis (RA) and to compare these with healthy individuals. Twenty-four women (12 healthy, 12 RA) were included. Evaluations were made with a JAMAR dynamometer, Health Assessment Questionnaire, and 3D kinematic analysis of global upper extremity during "jar opening motion." The time taken during "jar opening motion" was analyzed in 2 parts (Part 1, Part 2), with total time: part 1 + part 2. In addition, shoulder-to-table distance; elbow flexion angle; wrist extension angle; the area scanned and angular rotation by arm, forearm and hand were used in the analysis. Between groups, there was a statistical difference in: bilateral hand grip strength; part 1, part 2, total time; shoulder-to-table distance; elbow flexion angle; the area scanned by hand; angular rotation of arm and hand in favor of the healthy group (P < .05). In stepwise multiple regression analysis, the most predictive variable for disability was elbow flexion, explaining 53.9% of disability. Compared to healthy individuals, individuals with RA have slower motion, more elbow flexion, less hand grip strength, circular pattern in hand, rotation in arm and hand. Increased disability may result in greater load on elbow flexion.

Recent Insights Into the Role of Macrophages in Acute Gout.

Gout is a common type of inflammatory arthritis characterized by the presence of monosodium urate crystals (MSU) in the joints. Macrophages are believed to be involved in gout flares. It has long been recognized that resident macrophage and monocyte derived macrophages are distinct subsets and there have been attempts to investigate their roles in acute gout, respectively. Previous studies revealed that resident macrophages initiate and drive the inflammation, while monocyte derived macrophages differentiated into M1-like macrophages in response to MSU crystals. With the advancement of technologies, subpopulations of synovial resident macrophages have been defined with the characteristics more accurately described. Resident macrophages in the synovial lining layer showed an anti-inflammatory effect in rheumatoid arthritis, but specific Trpv4 depletion of them reduced MSU crystals induced murine arthritis. CD14+ monocytes in the synovial fluid from patients with gout exhibit phenotypes of anti-inflammatory as well as pro-inflammatory characteristics. Here, we review the main aspects of macrophages in the initiation and resolution of acute gout and try to clarify the specific role of each subpopulation. Building a reliable diagram of the effect of monocytes and macrophages during MSU crystals induced arthritis will bring us closer to targeting macrophages for improving the management of gout.

Dexamethasone-Loaded Radially Mesoporous Silica Nanoparticles for Sustained Anti-Inflammatory Effects in Rheumatoid Arthritis.

Radially mesoporous silica nanoparticles (RMSNs) with protonated amine functionality are proposed to be a dexamethasone (Dex) carrier that could achieve a sustained anti-inflammatory effect in rheumatoid arthritis (RA). High-capacity loading and a sustained release of target drugs were achieved by radially oriented mesopores and surface functionality. The maximum loading efficiency was confirmed to be about 76 wt%, which is about two times greater than that of representative mesopores silica, SBA-15. In addition, Dex-loaded RMSNs allow a sustained-release profile with about 92% of the loaded Dex for 100 h in vitro, resulting in 2.3-fold better delivery efficiency of Dex than that of the SBA-15 over the same period. In vivo evaluation of the inhibitory effects on inflammation in a RA disease rat model showed that, compared with the control groups, the group treated with Dex-loaded RMSNs sustained significant anti-inflammatory effects and recovery of cartilage over a period of 8 weeks. The in vivo effects were confirmed via micro-computed tomography, bone mineral density measurements, and modified Mankin scoring. The proposed Dex-loaded RMSNs prolonged the life of the in vivo concentrations of therapeutic agents and maximized their effect, which should encourage its application.

Biomarkers to Predict DMARDs Efficacy and Adverse Effect in Rheumatoid Arthritis.

Rheumatoid arthritis (RA), one of the most common immune system diseases, mainly affects middle-aged and elderly individuals and has a serious impact on the quality of life of patients. Pain and disability caused by RA are significant symptoms negatively affecting patients, and they are especially seen when inappropriate treatment is administered. Effective therapeutic strategies have evolved over the past few decades, with many new disease-modifying antirheumatic drugs (DMARDs) being used in the clinic. Owing to the breakthrough in the treatment of RA, the symptoms of patients who could not be treated effectively in the past few years have been relieved. However, some patients complain about symptoms that have not been reported, implying that there are still some limitations in the RA treatment and evaluation system. In recent years, biomarkers, an effective means of diagnosing and evaluating the condition of patients with RA, have gradually been used in clinical practice to evaluate the therapeutic effect of RA, which is constantly being improved for accurate application of treatment in patients with RA. In this article, we summarize a series of biomarkers that may be helpful in evaluating the therapeutic effect and improving the efficiency of clinical treatment for RA. These efforts may also encourage researchers to devote more time and resources to the study and application of biomarkers, resulting in a new evaluation system that will reduce the inappropriate use of DMARDs, as well as patients’ physical pain and financial burden.

Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry

BackgroundTo further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient’s satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients.MethodsThis is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient’s satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment.ResultsThis study included 2235 RA outpatients (406 males, 1829 females). In RA patients, “very satisfied” and “satisfied” were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50–64 years; OR 0.91; 65–74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas.ConclusionsIn this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

Women with Rheumatoid Arthritis have similar rates of postpartum maternal outcomes compared to women without autoimmune disease

ObjectiveLimited data exist on the effect of rheumatoid arthritis (RA) on maternal postpartum outcomes. Using a real-world, electronic health record (EHR) cohort, we assessed maternal postpartum outcomes in RA. MethodsIn a large, de-identified EHR, we identified possible RA deliveries using ≥1 delivery ICD-9 or ICD-10-CM codes and a validated RA algorithm. RA cases were required to be diagnosed by a rheumatologist on chart review. Maternal postpartum outcomes included rates of blood transfusion, rates of infection up to 6 weeks postpartum defined by a clinician, and length of hospital stay. We also identified deliveries to women without autoimmune diseases. ResultsWe identified 202 deliveries occurring after RA diagnosis and 596 deliveries to controls without autoimmune diseases. Postpartum infection rates were similar among RA patients and controls (8% vs. 4%, p = 0.10), as were red blood cell transfusion rates (2% vs. 2%, p = 1.00). RA case status was not significantly associated with postpartum infection (OR = 2.10, 95% CI 0.88 – 4.98, p = 0.09) but was significantly associated with preterm birth (OR = 2.11, 95% CI 1.38 – 3.23, p = 0.001). Corticosteroid use during pregnancy was common at 41%, while tumor necrosis factor inhibitor use was 13%. After adjusting for age at delivery and race, corticosteroid use at delivery was not associated with postpartum maternal infections but was associated with a significantly lower birthweight in RA cases. ConclusionWomen with RA have an increased risk of adverse pregnancy outcomes, particularly preterm birth. Our study highlights, however, that maternal postpartum outcomes such as postpartum infection and blood transfusion are not significantly increased in RA patients.

Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlled Study in the ArthritisPower® Registry.

IntroductionThe magnitude and frequency of temporally related methotrexate (MTX)-associated side effects in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients are difficult to quantify using traditional research methods. As proof of concept designed in part to implement digital data collection for remote patient monitoring, we conducted a study implementing self-controlled case series analytic methods to understand MTX-related symptoms in RA or PsA.MethodsIn study phase 1, adults with RA or PsA from the ArthritisPower® Registry (past or current oral MTX users) participated in a cross-sectional survey. In phase 2, current MTX users participated in a longitudinal study and completed the Patient-Reported Outcomes Measurement Information System (PROMIS®) 1-day nausea/vomiting and fatigue measure. Within-person change in PROMIS scores between risk (6–36 h post-dose) and control (96–144 h post-dose) windows were compared using mixed models.ResultsThe baseline survey was completed by 671 participants (mean age: 54 years, 88% female, 92% white, 79% with RA). Among current MTX users (353/671 [53%]), most reported MTX-associated side effects (216/353 [61%]), most frequently fatigue (161/353 [46%]). Among phase 2 participants with (n = 39) and without (n = 84) baseline nausea, mean increase in PROMIS nausea was 5.1 units (P < 0.0001) and 0.7 units (P = 0.135), respectively; among those with (n = 51) and without (n = 72) baseline fatigue, mean increase in PROMIS fatigue was 3.9 units (P = 0.0003) and 0.4 units (P = 0.554), respectively.ConclusionsDigital remote patient monitoring presents an opportunity to detect and address medication tolerability in real time. Using a novel study design to control for between-person confounding, the magnitude of nausea and fatigue experienced by participants with RA and PsA temporally related to weekly MTX use was substantial.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00398-6.

Combination of denosumab and biologic DMARDs in inflammatory muscle-skeletal diseases and connective tissue diseases.

Osteoporosis (OP) can complicate the course of rheumatic musculoskeletal diseases (RMDs) and connective tissue diseases (CTDs). Denosumab, a monoclonal antibody against RANK-L, showed beneficial effect in rheumatoid arthritis in inhibiting radiographic progression and erosive burden. We tested the efficacy, safety, and persistence on the treatment of the combination of biologic disease-modifying antirheumatic drugs (bDMARDs)/denosumab versus bDMARD in patients with RMD and CTD. This is a retrospective evaluation of a single center, including patients with RMD/CTD (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, and overlap syndromes) treatment with bDMARD/denosumab, compared to age, gender, disease, bDMARD, and conventional synthetic disease-modifying antirheumatic drugs-matched controls. Twenty-eight bDMARD/denosumab patients and 49 bDMARD patients were eligible. Despite a statistically significant difference during the first-year efficacy (due to the different baseline timepoint), there was no difference in the efficacy profile in the second year of treatment and in the safety profile (including local, systemic, and serious adverse events). Moreover, no statistically significant difference in the persistence of bDMARD treatment over 2 years of evaluation was found. The combination of bDMARD and denosumab was not an independent predictor of disease flare or bDMARD treatment withdrawal. The combination of bDMARD and denosumab does not alter the efficacy and the safety profile of the bDMARD in patients with RMD/CTD. Future studies verifying the radiological disease inhibition could support denosumab use in RMD/CTD other than rheumatoid arthritis, when complicated by OP.