Population Of Rheumatoid Arthritis Patients Research Articles

Association of Vitamin E Intake with All-Cause Mortality Among Individuals with Rheumatoid Arthritis: A Cohort Study from the NHANES 1999-2018

Background The relationship between dietary vitamin E intake and mortality rates among rheumatoid arthritis (RA) patients remains a relatively uncharted territory in nutritional epidemiology, underscoring an important gap in research. Objectives This study is to explore the potential association between dietary vitamin E intake and all-cause mortality in the RA patient population. Methods This longitudinal cohort study analyzed 2,906 RA patients aged 20 years or older who participated in the National Health and Nutrition Examination Survey from 1999 to 2018. Comprehensive data on mortality, dietary vitamin E intake, and pertinent confounding variables were systematically collected and analyzed using Cox regression and spline curve fitting to analyze the potential association. Results Following the adjustment for confounding factors, a significant inverse relationship was identified between dietary vitamin E intake and the risk of all-cause mortality in patients with RA. The adjusted hazard ratios (HRs) for the second (Q2), third (Q3), and fourth (Q4) quartiles of vitamin E intake were 0.85, 0.60, and 0.68, respectively. Non-linear modeling indicated a threshold effect characterized by a curve that associated dietary vitamin E intake with mortality risk (p = 0.016). An intake threshold of 7.097 mg/day was identified, below which each unit increment in vitamin E intake was associated with a 11.1% decrease in all-cause mortality risk (HR = 0.889). Conversely, for intakes surpassing this threshold, no significant relationship with mortality risk was detected (HR = 1.0038). Conclusion The findings of this study indicate a beneficial relationship between elevated dietary vitamin E intake and a reduced risk of all-cause mortality in RA patients. The dose-response relationship exhibits a non-linear pattern, featuring a critical inflection point at an intake of approximately 7.097 mg/day.

Is erectile dysfunction associated with osteoarthritis and rheumatoid arthritis? Insights from a population-based study.

The correlation between osteoarthritis (OA) and rheumatoid arthritis (RA), both significant components of arthritis, and erectile dysfunction (ED) has yet to be thoroughly investigated. In this study we aimed to assess the association of OA and RA with ED. In this observational study we used data from the National Health and Nutrition Examination Survey, which was conducted between 2001 and 2004. Various statistical analyses were employed to investigate the associations of OA and RA with ED, including multivariable logistic regression analysis and subgroup analysis. The primary outcome for this investigation was arthritis as assessed through self-reporting. In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA populations in comparison to the general population. Additional research is imperative to provide a deeper understanding of these correlations and their potential implications for both pathogenesis and treatment strategies. The research outcomes reported here may serve as a valuable guide for clinicians to assist OA and RA patientsin staying vigilant in addressing their sexual health concerns. We explored the association of OA and RA with ED. However, this is only a cross-sectional study. In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA patient populations in comparison to the general population. Ongoing research is imperative to provide a deeper understanding of these correlations.

Rheumatoid arthritis - medication dosage in chronic kidney disease.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.

Relationship of Complete Blood Count Derived Biomarkers With Methotrexate Resistance.

Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. Among the therapeutic agents, methotrexate remains a cornerstone of initial treatment. Complete blood count (CBC)-derived biomarkers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic immune response index (SIRI) have been extensively studied in various diseases. Still, their specific role in RA patients undergoing methotrexate treatment has not been investigated. Objective This study aimed to investigate the relationship of CBC-derived biomarkers with methotrexate resistance in newly diagnosed rheumatoid arthritis patients. Methods We performed a comprehensive analysis of 54 RA patients, divided into methotrexate-resistant (MTXR) and methotrexate-sensitive (MTXS) groups.Analysis of variance(ANOVA) was used to assess differences in hematological biomarkers between groups. Standard t-tests were used to compare specific biomarkers between the MTXR and MTXS groups. The chi-squared test was used to compare categorical variables between groups. Pearson's correlation test was also used to examine correlations between these biomarkers and Disease Activity Score 28 (DAS28) in both groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker to determine predictive ability. Results A statistically increased PLR ratio was observed in the MTXR group compared to the MTXS group. Significant correlations between DAS28 and NLR, PLR, SII, and SIRI were observed in the MTXR group. In contrast, these correlations were absent in the MTXS group. In addition to PLR, DAS28 and ESR were significantly higher in the MTXR group than in the MTXS group. None of these biomarkers showed prognostic value for methotrexate treatment outcomes. Conclusion PLR could be used as a biomarker for resistance to methotrexate treatment in a specific RA patient population. Increased PLR and ESR, together with higher DAS28, might be associated with a more pronounced inflammatory state in MTXR patients.

Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population.

Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavourable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi and biologic DMARDs (bDMARDs) in a large population of RA patients. RA patients starting a new bDMARD or JAKi between 1 August 2018 and 31 January 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during the study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposure time and confounders. The number of unique patients included was 15 191, with 28 481 patient-years on treatment with either JAKi (2373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient-years) during therapy with JAKi and 383 events (1.47 events/100 patient-years) during therapy with bDMARDs, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% CI: 0.70, 1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. In a large Dutch general RA population, the risk of cardiovascular events seems not to be different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded.

Proteomics analyses of human plasma reveal triosephosphate isomerase as a potential blood marker of methotrexate resistance in rheumatoid arthritis.

The objective of this study was to assess differentially expressed blood proteins between patients with active RA and patients in remission after MTX treatment, with the aim of identifying a biomarker of MTX resistance (MTXR). Two populations of RA patients treated with a stable dose of s.c. MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment, which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach. Untargeted proteomics analysis revealed eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis. A first step was achieved in the search for biomarkers of MTXR, with the identification of two actors in glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.

Infection incidence, timing, and dose dependency in rheumatoid arthritis patients treated with rituximab: a retrospective cohort study.

Rituximab (RTX) is a safe and effective treatment for rheumatoid arthritis (RA). However, there are some concerns about infection risk and preliminary data suggest dose and time dependency. This study aims to determine the infection incidence in a large real-life population of RA patients using RTX, with special focus on (ultra-)low dosing and time since last infusion. RA patients treated with 1000, 500 or 200 mg RTX per cycle between 2012 and 2021 at the Sint Maartenskliniek were included in a retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infection incidence rates, dose and time relations with RTX infusion were analysed using mixed-effects Poisson regression. Among 490 patients, we identified 819 infections in 1254 patient years. Most infections were mild and respiratory tract infections were most common. Infection incidence rates were 41, 54 and 71 per 100 patient years for doses of 200, 500 and 1000 mg. Incidence rate ratio (IRR) was significantly lower for 200 mg compared to 1000 mg (adjusted IRR 0.35, 95% CI 0.17-0.72, p = 0.004). In patients receiving 1000 or 500 mg RTX, infections seemed to occur more frequently within the first two months after infusion compared to later on in the treatment cycle, suggesting an association with peak concentration. Ultra-low dosing (200 mg) of RTX is associated with a lower risk of infections in RA. Future interventions focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may lower infection risk.

P140 Janus Kinase Inhibitors in Rheumatoid Arthritis Patients: Real-World Experience from a Regional Centre in UK

Abstract Background/Aims Tofacitinib and baricitinib were the first orally available, targeted synthetic Janus kinase (JAK) inhibitors approved for the treatment of rheumatoid arthritis (RA) in the UK. Evidence suggests that JAK inhibitors are as efficacious as biological DMARDs in the treatment of RA. Their safety profile has been demonstrated in long term extension studies and RCTs. However, real-world, long-term data remains as important in bridging the gap between controlled studies and routine practice. We report our initial real-world experience of a cohort of RA patients commenced on JAKi before the SARS-CoV-2 pandemic within a regional centre in the UK. Methods All patients commenced on JAKi for the treatment of RA between February 2018 and March 2020 were identified from our in-house database. Data was retrospectively collected from clinical notes and electronic health records from February 2018 up until April 2022. This included patient demographics, disease duration, serological status, concurrent csDMARD usage, history of bDMARD exposure, duration of use and reason for discontinuation of the drug if appropriate. DAS-28 scores were recorded at baseline and quarterly. SPSS (version 22.0) was used for data analysis. Results One hundred thirty patients were treated with JAK inhibitors (Tofacitinib 22%, Baricitinib 78%); 80% female, mean (S.D.) age 61.5 (12.3) years. 92 (70.8%) patients were seropositive. 70 (53.8%) patients were on concurrent csDMARDs and 23 (17.7%) on concurrent steroids. The mean number of previous bDMARDs was 1.8 ± 1.7; 41 (31.5%) were bDMARD naive. The mean baseline DAS-28 ESR (S.D.) score was 5.96 (0.96). There were significant differences in mean DAS-28 ESR scores (compared with baseline) of 1.54, 1.96, 2.41, 2.33 and 1.80 at 3, 6, 12, 18 and 24 months respectively (p &amp;lt; 0.0001). Mean DAS-28 ESR scores were not statistically significant between bDMARD naïve patients and those that had previously received bDMARDs. Overall JAKi retention rate was 66.9% with a mean follow up duration of 27.4±13.1 months. Persistence was 88.5%, 76.9%, 73.2% and 68.5% at 6, 12, 18, and 24 months, respectively. Of the 38 patients who stopped JAK inhibitors, 11 stopped due to inefficacy (6, primary inefficacy). 3 patients were lost to follow-up and 6 deceased. Cause of death was sepsis (2), venous thromboembolism (1) and unknown (3). 18 patients stopped because of adverse events (AEs). The most common AEs were recurrent infections (11), gastrointestinal side effects (9), lymphopenia (7), thromboembolic events (6) and herpes zoster (5). In total 6 (4.1%) patients had thromboembolic events which included pulmonary embolism (4) and deep vein thrombosis (1) and central retinal artery thrombosis (1). Conclusion JAK inhibitors in this real-world population of RA patients were effective in reducing disease activity and patients had high persistence rates. Recurrent infections, herpes zoster and thrombo-embolism remain adverse events of concern. Disclosure A. Ajibade: None. A. Hawarden: None. A. Leong: None. G. Hirsch: None. T. Adizie: None. S. Venkatachalam: None.

The Effect of Meditation, Mindfulness, and Yoga in Patients with Rheumatoid Arthritis.

Mind-body therapies (MBTs), including meditation, yoga, and mindfulness, create an interaction between the mind and body to enhance health. MBTs are perceived by both patients and healthcare professionals as valuable in the management of rheumatoid arthritis (RA), but the extent of this contribution is unclear, as are the patient subgroups who benefit most from MBTs. Therefore, this systematic literature review investigates the effects of meditation, mindfulness, and yoga in patients with RA. We searched four databases (PubMed, Embase, Web of Science (core collection, Chinese and Korean collection), and CINAHL). All studies were screened by two independent reviewers via the title/abstract/full text. The studies included any form of meditation/mindfulness/yoga as an intervention for RA. Animal studies, case reports, non-English articles, qualitative studies, conference abstracts, and articles without full-text access were excluded. Each study was assessed for its quality. Out of 1527 potentially eligible records, 23 studies were included. All three MBTs showed various effects on patient-reported outcomes, such as vitality, functioning, and mental health, as well as on disease activity markers. Mindfulness-based interventions mainly reduced the subjective disease activity parameters (e.g., joint tenderness, morning stiffness, and pain), rather than the objective disease activity parameters (e.g., swollen joints and C-reactive protein (CRP)). RA patients with recurrent depression may benefit more from these non-pharmacological therapies than patients without recurrent depression. This systematic literature review found that MBTs show added value in RA management, especially for patients with depressive symptoms. These non-pharmacological approaches, when used in addition to medication, might diminish polypharmacy in specific RA patient populations. Lay Summary: In recent decades, more attention has been given to the management of rheumatoid arthritis (RA) with options other than solely using medication. Such alternative options for patients to increase their quality of life are, for instance, meditation, yoga, and mindfulness. These examples of mind-body therapies (MBTs) are techniques that create an interaction between the mind and the bodily functions in order to obtain relaxation and enhance overall health. Although it is believed that these mind-body techniques are valuable in the management of RA, the extent of their contribution is still unclear, as is the question of if certain subgroups of patients benefit more from these complementary therapies. This systematic literature review investigated the effects of meditation, mindfulness, and yoga in patients with rheumatoid arthritis. A literature search was systematically performed within four different scientific databases by two independent reviewers. Out of 1527 potentially eligible articles, 23 studies were included. All three MBTs showed beneficial effects, which were mostly on the vitality, functioning, and mental health of patients with RA, but also on symptoms related to disease activity. RA patients with recurrent depression seemed to benefit more from these non-pharmacological therapies than patients without recurrent depression. Hence, we can conclude that MBTs show added value in the management of RA.

Predictors and complications of blood transfusion in rheumatoid arthritis patients undergoing total joint arthroplasty.

Our research investigated predictors of postoperative blood transfusion rate following total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA) and evaluated the incidence of complications in the transfusion group and non-transfusion group. The authors retrospectively analyzed risk factors among 320 RA patients who underwent elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) from January 2010 to December 2018. Demographic characteristics, laboratory results, medication history, and surgical protocol were gathered from electronic medical records. Univariable and multivariable logistic regression analyses were conducted to measure the impact of relevant variables on the need for transfusions. In addition, we compared the incidence of complications associated with transfusion. The cohort comprised 320 RA patients, aged 57.4 ± 12.0years, of whom 137 required postoperative blood transfusions and 183 did not. BMI, type of surgery, duration of surgery, disease activity score 28 (DAS28-CRP), tranexamic acid (TXA) administration, and preoperative hemoglobin (Hb) were all risk factors for transfusion after adjusting for the planned procedure. Previously published predictors, such as BMI, low preoperative hemoglobin, duration of surgery, procedure type (THA), were also identified in our analysis. Moreover, TXA administration and the DAS28-CRP showed the potential to influence risk. The incidence of postoperative complications was increased in patients who received blood transfusions compared to non-transfusion group. Our findings could help to identify RA patient population requiring blood transfusions, to ensure the necessary steps are adopted to limit blood loss and improve blood management strategies. Key Points • The risk factors for blood transfusion in rheumatoid arthritis patients undergoing total joint arthroplasty were BMI, the type of surgery, duration of surgery, TXA administration, DAS28-CRP, and preoperative hemoglobin. • The incidence of postoperative complications was increased in patients who received blood transfusions compared to non-transfusion group.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees

BackgroundChinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PurposeThe main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. Study designThe CERTAIN is a prospective, multicenter, observational disease registry. MethodsAdult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. ResultsIn the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. ConclusionsThe CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. RegistrationThe study was registered at ClinicalTrials.gov (NCT05219214).

Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethnic cohort in Singapore.

Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes. The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR1.06 [95% CI 1.04-1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02-3.09]), or Indian ethnicity (OR3.07 [95% CI 1.68-5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.

Handwork vs machine: a comparison of rheumatoid arthritis patient populations as identified from EHR free-text by diagnosis extraction through machine-learning or traditional criteria-based chart review

BackgroundElectronic health records (EHRs) offer a wealth of observational data. Machine-learning (ML) methods are efficient at data extraction, capable of processing the information-rich free-text physician notes in EHRs. The clinical diagnosis contained therein represents physician expert opinion and is more consistently recorded than classification criteria components.ObjectivesTo investigate the overlap and differences between rheumatoid arthritis patients as identified either from EHR free-text through the extraction of the rheumatologist diagnosis using machine-learning (ML) or through manual chart-review applying the 1987 and 2010 RA classification criteria.MethodsSince EHR initiation, 17,662 patients have visited the Leiden rheumatology outpatient clinic. For ML, we used a support vector machine (SVM) model to identify those who were diagnosed with RA by their rheumatologist. We trained and validated the model on a random selection of 2000 patients, balancing PPV and sensitivity to define a cutoff, and assessed performance on a separate 1000 patients. We then deployed the model on our entire patient selection (including the 3000). Of those, 1127 patients had both a 1987 and 2010 EULAR/ACR criteria status at 1 year after inclusion into the local prospective arthritis cohort. In these 1127 patients, we compared the patient characteristics of RA cases identified with ML and those fulfilling the classification criteria.ResultsThe ML model performed very well in the independent test set (sensitivity=0.85, specificity=0.99, PPV=0.86, NPV=0.99). In our selection of patients with both EHR and classification information, 373 were recognized as RA by ML and 357 and 426 fulfilled the 1987 or 2010 criteria, respectively. Eighty percent of the ML-identified cases fulfilled at least one of the criteria sets.Both demographic and clinical parameters did not differ between the ML extracted cases and those identified with EULAR/ACR classification criteria.ConclusionsWith ML methods, we enable fast patient extraction from the huge EHR resource. Our ML algorithm accurately identifies patients diagnosed with RA by their rheumatologist. This resulting group of RA patients had a strong overlap with patients identified using the 1987 or 2010 classification criteria and the baseline (disease) characteristics were comparable. ML-assisted case labeling enables high-throughput creation of inclusive patient selections for research purposes.

O32 Serious infection with tocilizumab compared to TNF-inhibitors and other bDMARDS in rheumatoid arthritis patients: does line of therapy matter?

Abstract Background/Aims In the real-world, tocilizumab is prescribed to a population of patients different from those prescribed TNF-inhibitors, often older with longer disease duration, worse functional status and more previous b- or tsDMARDs. The aim of this study was to evaluate if and how the risk of serious infection on tocilizumab and other bDMARDs differs when stratifying by line of therapy in a real-world population of rheumatoid arthritis patients. Methods We included patients registered in the BSRBR-RA treated with tocilizumab, etanercept, adalimumab, infliximab, certolizumab, abatacept or rituximab, including biosimilars. Primary outcome was the occurrence of a serious infection (defined as infection requiring hospitalisation, intravenous antibiotics or resulting in death). Primary covariate of interest was line of therapy (from first to fifth line of therapy). Every change to another b- or tsDMARD was considered a new line of therapy, but not a change between a bio-original and a biosimilar. Hazard ratios (HR) of serious infections were estimated using an inverse probability weighted Cox regression, based on a propensity score including baseline patient and disease characteristics, and adjusting for time in study (see table). The reference group was etanercept, which included the highest number of patients. Treatment exposure was analysed without and with stratification by line of therapy. Results A total of 33,916 treatment courses were included (Table) contributing to 62,532 years of follow-up. Compared to etanercept, participants starting abatacept, tocilizumab and rituximab were older, had more previous bDMARDs, longer disease duration and more comorbidities. The crude HR of serious infections were higher with infliximab and adalimumab, lower with certolizumab and rituximab, and not significantly different for abatacept and tocilizumab compared to etanercept. After adjustment, HR of serious infections were higher with tocilizumab, adalimumab and infliximab. However, when stratified by line of therapy, HR were no longer significantly different compared to etanercept for tocilizumab, adalimumab and infliximab for most lines of therapy. Conclusion Whilst initially there appears to be a difference in rates of serious infections between biologic therapies, line of therapy may be a confounding factor when comparing the risk of serious infections between bDMARDs. Disclosure K. Lauper: Honoraria; Gilead-Galapagos. Grants/research support; AbbVie. Other; AbbVie, Pfizer. L. Kearsley-Fleet: None. R. Davies: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; AbbVie. Grants/research support; Pfizer, BMS.

Model-Based Meta-Analysis Compares DAS28 Rheumatoid Arthritis Treatment Effects and Suggests an Expedited Trial Design for Early Clinical Development.

A nonlinear mixed effects modeling approach was used to conduct a model‐based meta‐analysis (MBMA) of longitudinal, summary‐level, baseline‐corrected 28‐joint Disease Activity Score (ΔDAS28) clinical trial data from seven approved rheumatoid arthritis (RA) drugs (abatacept, adalimumab, certolizumab, etanercept, rituximab, tocilizumab, and tofacitinib), representing 130 randomized clinical trials in 27,355 patients. All of the drugs except tocilizumab were found to have relatively similar ΔDAS28 time courses and efficacy (baseline‐corrected and placebo‐corrected) at 24 weeks and beyond of approximately 0.87–1.3 units in the typical RA patient population. Tocilizumab was estimated to have a differentially greater response of 1.99 at 24 weeks, likely due to its disproportionate effect on the acute‐phase cytokine interleukin‐6. Baseline DAS28, disease duration, percentage of male participants, and the year of conduct of the trial were found to have statistically significant effects on the timing and/or magnitude of ΔDAS28 in the control arms. Clinical trial simulations using the present MBMA indicated that abatacept, certolizumab, etanercept, tocilizumab, and tofacitinib would be expected to have a greater than 70% probability of showing a statistically significant difference vs. control at Week 6 with a sample size of ~ 30 patients per arm. In future RA clinical trials, an interim analysis conducted as early as 6 weeks after treatment initiation, with relatively small sample sizes, should be sufficient to detect the ΔDAS28 treatment effect vs. placebo.

Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective study.

Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated. To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern. The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.

Efficacy of baricitinib in treating rheumatoid arthritis: Modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting

BackgroundBaricitinib is a JAK inhibitor that blocks intracellular signalling pathways of inflammatory cytokines recommended for Rheumatoid arthritis (RA) patients not responding to initial treatment. Among RA extrareticular features, interstitial lung involvement is primarly characterized by fibrotic evolution. The aim of the present study was to analyse the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment. Materials and methods15 patients (median (IQR) 65 (55–66); 13% males and 74% smokers) treated with baricitinib were enrolled. 4 patients (27%) were classified as RA-ILD before baricitinib therapy. Our study is the first to evaluate adipokine levels in RA patients (including a small population with RA-ILD) after six months of baricitinib treatment with a novel multiplex method. ResultsThe modulatory effects of baricitinib on lipid mediators were associated with clinical and functional improvement, demonstrated by the significant increase in DLco and KCO percentages after six months of treatment. Baricitinib decreased the systemic inflammation by lowering expression of IL-6 and CRP and reducing ESR and serum concentrations of adiponectin. A significant reduction of KL-6 levels in RA-ILD patients after six months of baricitinib therapy reflects the stability of interstitial lung involvement in these patients. ConclusionBaricitinib was demonstrated to be a safe immune modulator that reduces the concentrations biomarkers of lung fibrosis and inflammation in RA patients, including a subgroup with interstitial lung involvement.

Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia.

The past decade in LGL leukemia research has seen increased pairing of clinical data with molecular markers, shedding new insights on LGL leukemia pathogenesis and heterogeneity. This review summarizes the current standard of care of LGL leukemia, updates from clinical trials, and our congruent improved understanding of LGL pathogenesis. Various clinical reports have identified associations between stem, bone marrow, and solid organ transplants and incidence of LGL leukemia. There is also a potential for underdiagnosis of LGL leukemia within the rheumatoid arthritis patient population, emphasizing our need for continued study. Preliminary results from the BNZ-1 clinical trial, which targets IL-15 along with IL-2 and IL-9 signaling pathways, show some evidence of clinical response. With advances in our understanding of LGL pathogenesis from both the bench and the clinic, exciting avenues for investigations lie ahead for LGL leukemia.

Incidence of Free of Charge Physiotherapy in a Danish National Cohort of Stroke, Parkinson's Disease, Multiple Sclerosis and Rheumatoid Arthritis Patients.

BackgroundDenmark is a welfare state with a publically funded healthcare system that includes the right to free of charge physiotherapy (FCP) for patients with chronic or progressive disease who fulfill strict criteria. The aim of this study was to investigate the incidence of referral to FCP in patients with a hospital diagnosis of stroke, multiple sclerosis (MS), Parkinson’s disease (PD) and rheumatoid arthritis (RA) between 2007 and 2016.MethodsThe study was register-based and included data from The Danish National Patient Registry and The National Health Service Registry. The study population included the four largest disease groups receiving FCP in Denmark. The incidence of receiving FCP was reported as the cumulated incidence proportion (CIP).ResultsThe study showed that FCP was mainly initiated within the first 2 years after diagnosis. The 2-year CIP was 8% for stroke patients, 53% for PD patients, 49% for MS patients, and 16% for RA patients. The proportion of patients referred to FCP generally increased over the period of the study due to more patients being referred from medical specialists in primary care.ConclusionThis study found substantial differences in the incidence of referral to FCP in a Danish population of stroke, PD, MS and RA patients.

Established rheumatoid arthritis - Redefining the concept.

During the last few years, there has been a shift of focus in rheumatoid arthritis (RA) research towards earlier disease states. The terms early and established RA are inseparable, and having a clear definition of these two terms is crucial in conducting research and trying to understand the immunopathological mechanisms behind these different disease states. Established RA has been connected to chronic inflammation and a high burden of long-standing disease, with joint damage and comorbidities as a consequence of chronic inflammation. A chronological definition does not ensure us clear differentiation between early and established disease, because diagnosis can be delayed significantly. Similarly, a radiological definition does not ensure a clear differentiation either, as there is significant heterogeneity in the RA patient population, with some patients never developing structural damage, even after many years of disease. As the focus is now more on the early stages of disease, we propose to use the term established RA from the time of a definite clinical diagnosis of RA, irrespective of the symptoms' duration or the presence of irreversible damage, to distinguish established disease to a stage of undifferentiated arthritis (UA) or risk for developing RA, which might never progress to RA.