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33152484 COVID-19 in French patients with chronic inflammatory rheumatic diseases: Clinical feature 2021 Jan OBJECTIVE: To explore how patients with chronic inflammatory rheumatic diseases (CIRDs) coped with their disease during the COVID-19 pandemic and to identify possible predictive factors of SARS-CoV-2 infection in this population. METHODS: Patients followed in a single rheumatology department in France or registered on the Spondy+ platform, a secure e-health platform for spondyloarthritis patients, were invited to complete a questionnaire focused on their experiences around COVID19 symptoms, testing and medications access during the lockdown period. Descriptive statistics were used to report questionnaire's results. Factors associated with COVID-19 or with treatment discontinuation were assessed by logistic regression. RESULTS: We obtained 655 answers from the 2,081 contacted patients: 474 with spondyloarthritis, 129 with rheumatoid arthritis and 52 with psoriatic arthritis. The population was predominantly female (61.8%) with a mean age of 51.0±13.4 years. Incidence of COVID-19 was 6.9% (95%CI: 5.1-9.2%), including 12 confirmed and 33 highly suspicious cases. No death was observed and five patients needed to be hospitalized. Factors independently associated with an increased risk of infection were SARS-CoV-2 exposure, younger age and non-smoking. More than 30% of the patients suspended or decreased the dosage of one of their drugs during the lockdown period. This was followed in 63.4% of them by increased disease activity. Modifications were mostly motivated by fear of contagion (79.3%). CONCLUSION: We did not observe any increase of incidence or severity of COVID-19 in patients suffering of the 3 most common CIRDs. This survey also adds evidence of the safety of anti-rheumatic drugs use regarding COVID-19.
34567896 Legionella Coinfection in a Patient With COVID-19 Pneumonia. 2021 Aug Bacterial superinfection is a well-reported complication of viral pneumonia leading to significantly increased morbidity and mortality. Such superinfections have been reported in patients with pathogenic coronaviruses including severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), but there are scant reports pertaining to superinfection in the context of coronavirus disease 2019 (COVID-19). We report a case of a middle-aged man who presented with worsening shortness of breath in the context of COVID-19 complicated by superimposed Legionella pneumophilia pneumonia. This case serves to highlight the possibility of bacterial superinfections and to be aware of such possibilities when patients are not responding to standard courses of treatment for COVID-19 as quick clinical deterioration is likely to develop.
33418032 Therapeutic potential of russelioside B as anti-arthritic agent in Freund's adjuvant-induc 2021 Apr 24 ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma species are traditional edible herbs used in folkloric medicine as antidiabetic, antioxidant, antipyretic, antirheumatic, anti-inflammatory and anthelmintic agents. C. quadrangula was selected in this study to document the traditional use of the genus as anti-rheumatic treatment and the possible mechanisms of action. AIM OF THE STUDY: The higher mortality rates and shorter survival among the patients suffering from rheumatoid arthritis (RA) led to the increased interest on searching for new treatments for RA. Russelioside B (RB), a major pregnane glycoside found in C. quadrangula, was evaluated as a new anti-rheumatic agent. MATERIALS AND METHODS: The n-butanol fraction of C. quadrangula was chromatographed on a silica gel column to isolate RB. The adjuvant-induced arthritis (AIA) model was established in rats by intradermal injection of complete Freund's adjuvant (CFA) to evaluate its anti-arthritic effect. Ibuprofen was used as a reference drug. Forty rats were randomly divided into 5 groups (n = 8): normal (NOR); CFA model (CFA); ibuprofen, 5 mg/kg; RB, 25 mg/kg and RB, 50 mg/kg. The treatments were initiated from day 16 when AIA model was established and continued up to day 40. Serum diagnostic rheumatoid markers, inflammatory cytokines, oxidative stress biomarkers, cartilage and bone degeneration enzymes were assessed. RESULTS: RB at 50 mg/kg b. wt., showed significant decreases in the activities of hyaluronidase and β-glucouronidase enzymes as well significant decreases in the levels of proinflammatory cytokines as nuclear factor-kappa-B (NF-κB), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) compared to the CFA group; 11.04 ± 0.61 pg/mg protein, 4.35 ± 0.25 pg/mg protein, 3.32 ± 0.13 pg/mg protein & 2.75 ± 0.14 pg/mg protein for RB, 50 mg/kg b. wt. group vs. 25.33 ± 2.13 pg/mg protein, 25.65 ± 2.1 pg/mg protein, 22.20 ± 1.34 pg/mg protein & 13.27 ± 1.40 pg/mg protein for the arthritic group, respectively. The total antioxidant capacity (TAC) was significantly restored to normal values in RB, 50 mg/kg treated rats (4.01 ± 0.09 nmol/mL vs. 3.71 ± 0.27 nmol/mL) and the levels of myeloperoxidase (MPO) reduced by 10-folds of the CFA arthritic group. Bone histomorphometry revealed that RB treatment significantly attenuated the CFA-induced bone loss in a dose-dependent manner. CONCLUSIONS: These findings suggested that the anti-arthritic effect of RB was mediated through the reduction of the rheumatoid markers, anti-inflammatory and antioxidant action, inhibition of cartilage and bone degenerative enzymes as well as attenuation of bone loss and osteoclastogenesis.
34943495 Ability to Participate in Social Activities of Rheumatoid Arthritis Patients Compared with 2021 Dec 2 OBJECTIVES: To compare the ability to participate in social activities among rheumatoid arthritis patients with other rheumatic disease patients and identify potentially implicated factors. PATIENTS AND METHODS: Between June and November 2019, we consecutively selected patients aged ≥18 years with RA (defined according to ACR/EULAR 2010), SpA (ASAS/EULAR 2010), and SLE (ACR 1997). MAIN OUTCOME MEASURES: Ability to participate in social roles and activities evaluated using the PROMIS score v2.0 short-form 8a (PROMIS-APS). SECONDARY OUTCOMES: Participation in social activities according to a series of variables (mobility, depression, satisfaction with social relationships, social isolation, company, emotional support, instrumental support, and support via information). We evaluated the association between the ability to participate in social activities and associated variables using multivariable linear regression analysis. RESULTS: The study population comprised 50 patients with RA (33.1%), 51 patients (33.8%) with SpA, and 50 patients (33.1%) with SLE. The mean PROMIS-APS scores were similar in the three groups. The multivariable analysis for the whole sample showed that the ability to participate in social activities was inversely associated with depression and directly with social satisfaction, mobility, company, and age. The stratified analysis revealed an inverse association between inflammatory activity and ability to participate in social activities in patients with RA and SpA, but not in those with SLE. CONCLUSION: All patients with RA, SpA, and SLE had a similar ability to participate in social activities. This was associated with other psychosocial factors (social satisfaction, mobility, company, depression) and clinical factors (age and inflammatory activity).
34917185 Influence of anti-TNF therapy and homocysteine level on carotid intima-media thickness in 2022 Jan It is a well-known fact that disruptions in the immune system and systemic inflammation are associated with accelerated atherosclerosis in rheumatoid arthritis (RA) patients. Elevated levels of tumor necrosis factor α (TNF-α), a major pro-inflammatory cytokine, are involved in endothelial cell activation of medium and large arteries, leading to increased endothelial permeability, generation of superoxide anion radical and hydrogen peroxide, and decreased availability of nitric oxide (NO). The present study aims to determine the influence of anti-TNF therapy and homocysteine (Hcy) levels on the carotid intima-media thickness (IMT) in patients with RA. Assessments were performed on 115 patients diagnosed with RA on biological treatment to determine the evolution of IMT and Hcy levels. Carotid ultrasonography was used to assess the IMT, as a fast and easy tool for the prediction of cardiovascular events in patients with RA. The first measurement of IMT was noted as IMT1, followed by a second measurement after 1 year, noted as IMT2. The group of patients was divided into approximately three equal groups, each being treated with a different biological product, respectively, etanercept, adalimumab, and infliximab. In the 3 groups, after 1 year of anti-TNF-α therapy, IMT2 progression was significantly reduced compared to baseline. No significant differences were found among the three groups of treatment. A strong association was observed between IMT1-IMT2 in the etanercept group (P<0.001, r=0.758), in the adalimumab group (P<0.001, r=0.761) and in the infliximab group (P<0.001, r=0.829). The low level of Hcy2 after 12 months of anti-TNF-α therapy was significantly correlated with a decrease in IMT2 (P<0.001) in patients who had a high level of Hcy and IMT >0.9 mm at baseline. The results from the present study showed that biological treatment and the low level of homocysteinemia reduced the cardiovascular risk in RA, regardless of the treatment chosen (infliximab, adalimumab, or etanercept).
34816388 Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patient 2022 Feb INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).
34746187 Does Use of Acupuncture Reduce the Risk of Type 2 Diabetes Mellitus in Patients With Rheum 2021 Objectives: Although acupuncture is often advocated for patients with rheumatoid arthritis (RA), its efficacy for type 2 diabetes mellitus (T2DM), a common metabolic disease among RA cohorts, has not yet been established. This retrospective cohort study aimed to determine the association between acupuncture use and the development of T2DM among them. Methods: Data were collected from 1999 through 2008 for individuals aged 20-70 years in the nationwide insurance database of Taiwan. From them, we extracted 4,941 subjects within newly diagnosed RA and being T2DM free at baseline. A total of 2,237 patients had ever received acupuncture, and 2,704 patients without receiving acupuncture were designated as a control group. All of them were followed to the end of 2013 to identify T2DM incidence. The Cox proportional hazards regression model was utilized to obtain the adjusted hazard ratio (HR) for acupuncture use. Results: Compared with the RA subjects without use of acupuncture, the incidence of T2DM was lower for those who received acupuncture, with the incidence rates of 24.50 and 18.00 per 1,000 person-years (PYs), respectively. After adjusting for potential confounders, use of acupuncture was significantly related to the lower T2DM risk, with the adjusted HR of 0.73 [95% confidence interval (CI) 0.65-0.86]. Those who used acupuncture for more than five sessions had the greatest benefit in lowering the susceptibility to T2DM. Conclusion: Adding acupuncture into conventional treatment for RA was found to be related to lower risk of T2DM among RA patients. Further clinical and mechanistic studies are warranted.
34501260 The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Inters 2021 Aug 25 We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.
34258468 The effect of propolis supplementation on inflammatory factors and oxidative status in wom 2021 Sep BACKGROUNDS AND AIMS: Rheumatoid arthritis (RA), is immune-inflammatory disease which is associated with great pain and disability. Overproduction of pro-inflammatory cytokines and oxidative stress play an important role in RA pathogenesis and related outcomes. The aim of this study was to evaluate the effects of propolis on inflammatory biomarkers and oxidative stress status in RA patients. METHODS/DESIGN: Randomized, placebo-controlled, and double-blind clinical trial aiming to recruit 48 patients with RA. Block randomization will be used. An intervention group will receive 500 mg/twice a day propolis capsules for 3 months and control group will receive the placebo for the same dose and duration. The oxidative stress status (malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), and inflammatory biomarkers (interleukin-17 (IL-17), Tumor necrosis factor alpha (TNF-α), High-sensitivity C-reactive protein (hs-CRP)), lipid profile (total cholesterol (TC), high density lipoprotein (HDL-c), low density lipoprotein (LDL-c), and triglyceride (TG)) and also physical activity, anthropometric indices, clinical and nutritional status will be measured at beginning and end of this study. The primary analysis will be based on theintention-to-treat principle. DISCUSSION: If this randomized clinical trial shows the reduction in inflammatory cytokines and oxidative stress and improves clinical outcome, it would provide evidence for other clinical trials to evaluate the efficacy of propolis supplementation in RA patients.
33772743 Cost-effectiveness of Triple Therapy vs. Biologic Treatment Sequence as First-line Therapy 2021 Jun INTRODUCTION: A clinical trial (RACAT) reported the noninferiority of triple therapy compared to biologic agents (etanercept + methotrexate), and previous studies confirmed that biologic disease-modifying antirheumatic drugs (bDMARDs) are more expensive but less beneficial than triple therapy for patients with rheumatoid arthritis (RA) in whom methotrexate (MTX) fails. However, from the perspective of the Chinese healthcare system, the cost-effectiveness of triple therapy versus bDMARD treatment sequences as a first-line therapy for patients with RA is still unclear. METHODS: An individual patient simulation model was used to extrapolate the lifetime cost and health outcomes by tracing patients from initial treatment through switches to further treatment lines in a sequence. Therapeutic efficacy and physical function were evaluated using the American College of Rheumatology (ACR) response, 28-Joint Disease Activity Score (DAS28), and Health Assessment Questionnaire score. All input parameters in the model were derived from published studies, national databases, local hospitals, and experts' opinions. Both direct costs and indirect costs were taken into consideration. Probabilistic and one-way sensitivity analyses were performed to test the uncertainty of the model, as were multiple scenario analyses. RESULTS: The lifetime analysis demonstrated that triple therapy was associated with lower costs and quality-adjusted life years (QALYs) than bDMARD sequences. These resulted in incremental cost-effectiveness ratios (ICERs) ranging from $87,090/QALY to $104,032/QALY, higher than the willingness-to-pay (WTP) threshold in China ($30,950/QALY). The baseline DAS28 impacted the model outcomes the most. Scenario analyses indicated that adding triple therapy to bDMARD sequences as a first-, second-, third-, or fourth-line therapy is very cost-effective, at a WTP of $10,316/QALY. CONCLUSIONS: From a Chinese payer perspective, triple therapy as first-line treatment in treatment sequence could be regarded as cost-effectiveness option for patients who failed MTX, compared to bDMARDs as first-line treatment, and instead of prescribing triple therapy as a substitute for bDMARDs as a first-line treatment, adding triple therapy to the bDMARD treatment sequence is likely to be very cost-effective for patients with active RA compared to bDMARD sequences.
33672771 Exploring the Role of Interleukin-6 Receptor Inhibitor Tocilizumab in Patients with Active 2021 Feb 20 BACKGROUND: The aim of our study was to explore the influence of weekly subcutaneous administration of interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) on periodontal status in a local longitudinal study of patients with rheumatoid arthritis (RA) and periodontal disease (PD). METHODS: We performed a 6-month prospective study in 51 patients with chronic periodontitis and moderate-to-severe RA starting TCZ in accordance with local recommendations. Extensive rheumatologic (clinical activity, inflammatory, serological biomarkers) and periodontal (visible plaque index, gingival index, bleeding on probing, probing pocket depth, clinical attachment loss) assessments were done. Changes in RA activity and periodontal status were reassessed after 3 and 6 months. RESULTS: We demonstrated significant correlations between periodontal status, disease activity, and serologic biomarkers (p < 0.05). Tocilizumab significantly improved the gingival index scores and decreased the number of sites with bleeding on probing after only 3 months (p < 0.05), while the probing pocket depth significantly decreased after 6 months; overall, clinical attachment loss presented only slight changes without any statistical significance as well as teeth count and plaque levels (p > 0.05). CONCLUSION: IL-6 inhibition is able to improve periodontal outcomes in patients with RA and concomitant PD, which is essentially related to a dramatic decrease in serum inflammatory mediators.
34791051 During development of rheumatoid arthritis, intermetatarsal bursitis may occur before clin 2021 Nov 13 OBJECTIVES: Intermetatarsal bursitis (IMB) represents juxta-articular synovial inflammation of the intermetatarsal bursae. Recent MRI-studies identified IMB as feature of early RA, but whether IMB already occurs in the pre-arthritic phase is unknown. We performed a large MRI-study in clinically suspect arthralgia (CSA) to assess the occurrence and prognostic value of IMB. METHODS: 577 consecutive CSA-patients underwent contrast-enhanced MRI of the forefoot, metacarpophalangeal joints and wrist. MRIs were evaluated for subclinical synovitis/tenosynovitis/osteitis in line with the RA MRI scoring system (summed as RAMRIS-inflammation) and for IMB. IMB was considered present if uncommon in the general population at the same location (i.e. size scored above the 95th-percentile in age-matched symptom-free controls). The relation of IMB with other MRI-detected subclinical inflammation synovitis/tenosynovitis/osteitis) was studied. Cox-regression assessed the association with clinical arthritis development during median 25 months follow-up. ACPA-stratification was performed. RESULTS: At presentation with CSA, 23% had IMB. IMB was more frequent in ACPA-positive than ACPA-negative CSA (47% vs 19%,p< 0.001). Patients with IMB were more likely to also have subclinical synovitis (OR 3.4 (95%CI 1.8-6.5)) and tenosynovitis (5.9(2.8-12.6)). IMB conferred higher risk of developing arthritis (HR 1.6(1.0-2.7) adjusted for other subclinical inflammation). IMB-presence predicted arthritis development in ACPA-positive CSA (adjusted HR 2.2(1.0-4.7)), but not in ACPA-negative CSA-patients (0.8(0.4-1.7)). CONCLUSION: Approximately a quarter of CSA-patients have IMB, which is frequently accompanied by subclinical synovitis and tenosynovitis. IMB precedes development of clinical arthritis, particularly in ACPA-positive CSA. These results reinforce the notion that juxta-articular synovial inflammation is involved in the earliest phases of RA-development.
34447903 Patient Empowerment: Apni Jung (Our Fight) against Rheumatoid Arthritis for South Asian Po 2021 Jun Covid-19 has affected many populations in the UK, and ethnic minority communities in particular. People from ethnic minority communities living with long-term chronic diseases have shown to be less engaging with self-management and report having poor medication adherence. The main reason to this problem is the way information is delivered to non-English speaking patients. This editorial discusses an innovation to over this barriers in rheumatology practice.
34977091 Cardiovascular Autonomic Function Changes and Predictors During a 2-Year Physical Activity 2021 Background: Chronic inflammation leads to autonomic dysfunction, which may contribute to the increased risk of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA). Exercise is known to restore autonomic nervous system (ANS) activity and particularly its parasympathetic component. A practical clinical tool to assess autonomic function, and in particular parasympathetic tone, is heart rate recovery (HRR). The aim of this substudy from the prospective PARA 2010 study was to determine changes in HRR post-maximal exercise electrocardiogram (ECG) after a 2-year physical activity program and to determine the main predictive factors associated with effects on HRR in RA. Methods: Twenty-five participants performed physiotherapist-guided aerobic and muscle-strengthening exercises for 1 year and were instructed to continue the unsupervised physical activity program autonomously in the next year. All participants were examined at baseline and at years 1 and 2 with a maximal exercise ECG on a cycle ergometer. HRR was measured at 1, 2, 3, 4, and 5 min following peak heart rate during exercise. Machine-learning algorithms with the elastic net linear regression models were performed to predict changes in HRR1 and HRR2 at 1 year and 2 years of the PARA program. Results: Mean age was 60 years, range of 41-73 years (88% women). Both HRR1 and HRR2 increased significantly from baseline to year 1 with guided physical activity and decreased significantly from year 1 to year 2 with unsupervised physical activity. Blood pressure response to exercise, low BMI, and muscular strength were the best predictors of HRR1/HRR2 increase during the first year and HRR1/HRR2 decrease during the second year of the PARA program. Conclusion: ANS activity in RA assessed by HRR was improved by guided physical activity, and machine learning allowed to identify predictors of the HRR response at the different time points. HRR could be a relevant marker of the effectiveness of physical activity recommended in patients with RA at high risk of CVD. Very inactive and/or high CVD risk RA patients may get substantial benefits from a physical activity program.
34897491 High incidence of serious infections requiring hospitalisation in human T-cell leukaemia v 2021 Oct 16 OBJECTIVES: We aimed to assess the clinical features of human T-cell leukaemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Furthermore, we investigated the impact of HTLV-1 infection on incidences of serious infections requiring hospitalisation (SIH) and malignancies. METHODS: A total of 150 sex- and age-matched HTLV-1-negative and 50 HTLV-1-positive RA patients were enrolled from the HTLV-1 RA Miyazaki Cohort Study. Clinical and laboratory data were collected from this cohort database. The incidence rate (IR) for SIH and malignancies from 2015 to 2020 was analysed. RESULTS: The median age and female ratio in the study population were 70 years old and 80%, respectively. Although no differences were found in inflammatory marker values between the two groups, the patient global assessment and Health Assessment Questionnaire scores were higher in HTLV-1-positive RA patients. In HTLV-1-negative RA patients, the IR for SIH was 6.37/100 person-years (PY) and 1.32/100 PY for malignancies. In HTLV-1-positive RA patients, SIH occurred in 11.1/100 PY and malignancies in 2.46/100 PY. The crude IR ratio comparing SIH between two groups was 1.74 (95% confidence interval, 1.04-2.84), which was a significant increase. CONCLUSIONS: HTLV-1-positive RA patients may worsen RA symptoms. HTLV-1 may be a risk factor for SIH.
34875040 Screening for Preclinical Parenchymal Lung Disease in Rheumatoid Arthritis. 2021 Dec 7 OBJECTIVES: Pulmonary disease is a common extraarticular manifestation of rheumatoid arthritis (RA) associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). METHODS: RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional, and radiologic evaluations. High resolution computed tomography (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. RESULTS: Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titers, and diffusion abnormalities. A significant proportion of preclinical emphysema occurred amongst never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory, or functional measures. CONCLUSION: We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even amongst never smokers. As clinical, laboratory, and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.
34228217 Qualitative and psychometric approaches to evaluate the PROMIS pain interference and sleep 2021 Jul 6 BACKGROUND: Patients with rheumatoid arthritis (RA) commonly experience pain despite the availability of disease-modifying treatments. Sleep disturbances are frequently reported in RA, with pain often a contributing factor. The Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Sleep Disturbance item banks were initially developed to provide insights into the patient experience of pain and sleep, respectively, though they were not specifically intended for use in RA populations. This study evaluated the content validity of the PROMIS Pain Interference and Sleep Disturbance item banks in RA and identified relevant content for short forms for patients with RA that achieved high measurement precision across a broad range of health. METHODS: A qualitative approach consisting of hybrid concept elicitation and cognitive debriefing interviews was used to evaluate the content validity of the item banks in RA. Interviews were semi-structured and open-ended, allowing a range of concepts and responses to be captured. Findings from the qualitative interviews were used to select the most relevant items for the short forms, and psychometric evaluation, using existing item-response theory (IRT) item parameters, was used to evaluate the marginal reliability and measurement precision of the short forms across the range of the latent variables (i.e. pain interference and sleep disturbance). RESULTS: Thirty-two participants were interviewed. Participants reported that RA-related pain and sleep disturbances have substantial impacts on their daily lives, particularly with physical functioning. The PROMIS Pain Interference and Sleep Disturbance item banks were easy to understand and mostly relevant to their RA experiences, and the 7-day recall period was deemed appropriate. Qualitative and IRT-based approaches identified short forms for Pain Interference (11 items) and Sleep Disturbance (7 items) that had high relevance and measurement precision, with good coverage of the concepts identified by participants during concept elicitation. CONCLUSION: Pain and sleep disturbances affect many aspects of daily life in patients with RA and should be considered when novel treatments are developed. This study supports the use of the PROMIS Pain Interference and Sleep Disturbance item banks in RA, and the short forms developed herein have the potential to be used in clinical studies of RA.
34222289 Remission Induced by TNF Inhibitors Plus Methotrexate is Associated With Changes in Periph Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39-0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63-1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.
34211592 Biomarkers for interstitial lung disease and acute-onset diffuse interstitial lung disease 2021 Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.
34063142 Angiotensin-Inhibiting Drugs Do Not Impact Disease Activity in Patients with Rheumatoid Ar 2021 May 5 OBJECTIVES: Besides their proven effectivity in decreasing the risk of cardiovascular events, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARBs) are likely to possess anti-inflammatory properties as well. This study aims to investigate whether the use of ACEi and ARBs additionally lowers disease activity in patients with rheumatoid arthritis (RA). METHODS: In this cross-sectional study, we used ARBs or ACEi to study RA patients who had at least one DAS28-CRP measurement during a one-year period. A control group of RA patients without ACEi/ARBs was randomly selected. The primary outcome was the difference between the DAS28-CRP scores of ACEi/ARBs users and controls. The secondary outcomes were the differences between administered dosages of csDMARDs and bDMARDs for users and controls, respectively; these were expressed in defined daily dose (DDD). Confounders were included in the multiple regression analyses. RESULTS: A total of 584 ACEi/ARBs users and 552 controls were finally examined. Multiple linear regression analyses showed no association between the use of ACEi or ARBs and the DAS28-CRP scores (ACEi factor 1.00, 95% CI 0.94-1.06; ARBs 1.02, 95% CI 0.96-1.09), nor with the dosage of csDMARDs (ACEi 0.97, 95% CI 0.89-1.07; ARBs 0.99, 95% CI 0.90-1.10). Furthermore, the use of ACEi was not associated with reduced dosages of bDMARDs (OR 1.14, 95% CI 0.79-1.64), whereas ARBs users tended to use less bDMARDs (1.46, 95% CI 0.98-2.18, p = 0.06). CONCLUSION: In this study, the use of either ACEi or ARBs in RA patients had no impact on disease activity as measured by the DAS28-CRP. A trend towards lower bDMARD dosages was observed in ARBs users, but the significance of this finding is still unclear.