Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases

Background METARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers. Methods The BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of <18.5 kg/m2 (underweight), 18.5 to <25 kg/m2 (normal weight), 25 to <30 kg/m2 (overweight), and ≥30 kg/m2 (obese) were used. Patients were stratified by age and sex, and compared to controls from the German Ageing Survey. Associations between BMI and markers of disease activity were analysed with non-parametric tests and linear models. Results Data from 1207 (CAPEA), 12,230 (RABBIT), and 3424 (National database) RA patients and 6202 population controls were evaluated. The mean age was 56, 56, 62, and 62 years, respectively, the mean disease duration was 13 weeks, 9.9 years, and 13.5 years, respectively, and the mean disease activity score (DAS28) was 5.1, 5.2, and 3.1, respectively. In all RA cohorts, obesity was more frequent (23.8 %, 23.4 %, 21.4 %, respectively) than in controls (18.2 %). This applied to all age groups <70 years, was independent of disease duration, and was more pronounced in females. In all cohorts, the age at RA onset was associated with BMI, being higher in overweight/obese patients compared to normal-weight patients. Current smoking was negatively associated with BMI. Linear analyses revealed increased erythrocyte sedimentation rate (ESR) values in underweight and obese females, and an increasing disparity between tender joint counts (TJCs) and swollen joint counts (SJCs) in higher BMI categories. Conclusions Compared to the general population, a higher prevalence of obesity was observed in all RA cohorts. The dominance of obesity in females and the different behaviour of disease activity markers in relation to the BMI in females indicate that additional parameters need to be considered when analysing the impact of obesity on inflammation in RA

Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low – results from RABBIT, the German biologics register

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis – Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2–3.2)); ARA remission, OR 2.05 (95% CI 1.2–3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7–8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04–4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only

Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis

Background The aim was to estimate the impact of individual risk factors and treatment with various disease-modifying antirheumatic drugs (DMARDs) on the incidence of myocardial infarction (MI) in patients with rheumatoid arthritis (RA). Methods We analysed data from 11,285 patients with RA, enrolled in the prospective cohort study RABBIT, at the start of biologic (b) or conventional synthetic (cs) DMARDs. A nested case–control study was conducted, defining patients with MI during follow-up as cases. Cases were matched 1:1 to control patients based on age, sex, year of enrolment and five cardiovascular (CV) comorbidities. Generalized linear models were applied (Poisson regression with a random component, conditional logistic regression). Results In total, 112 patients developed an MI during follow-up. At baseline, during the first 6 months of follow-up and prior to the MI, inflammation markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) but not 28-joint-count disease activity score (DAS28) were significantly higher in MI cases compared to matched controls and the remaining cohort. Baseline treatment with DMARDs was similar across all groups. During follow-up bDMARD treatment was significantly more often discontinued or switched in MI cases. CV comorbidities were significantly less often treated in MI cases vs. matched controls (36 % vs. 17 %, p < 0.01). In the adjusted regression model, we found a strong association between higher CRP and MI (OR for log-transformed CRP at follow-up: 1.47, 95 % CI 1.00; 2.16). Furthermore, treatment with prednisone ≥10 mg/day (OR 1.93, 95 % CI 0.57; 5.85), TNF inhibitors (OR 0.91, 95 % CI 0.40; 2.10) or other bDMARDs (OR 0.85, 95 % CI 0.27; 2.72) was not associated with higher MI risk. Conclusions CRP was associated with risk of MI. Our results underline the importance of tight disease control taking not only global disease activity, but also CRP as an individual marker into account. It seems irrelevant with which class of (biologic or conventional) DMARD effective control of disease activity is achieved. However, in some patients the available treatment options were insufficient or insufficiently used - regarding DMARDs to treat RA as well as regarding the treatment of CV comorbidities

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD

Objectives: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. Methods Using an online questionnaire (www.COVID19-rheuma.de.), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. Results Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males;63 females;1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. Conclusions: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic

data from the EULAR COVAX physician-reported registry

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND: There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs. OBJECTIVES: To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). METHODS: We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. RESULTS: A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20-30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. CONCLUSIONS: This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.publishersversionpublishe

a European registries collaborative project

Funding: Individual registries had entered into agreements with pharmaceutical companies (AbbVie, BMS, Hospira, MSD, Pfizer, Roche, UCB, Samsung and Eli Lilly). The pharmaceutical companies funding these registers were, however, not involved in the planning of the project, the statistical analyses, the interpretation of the results or the decision to publish.BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes. METHODS: Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD. RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population. CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.publishersversionpublishe

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe