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

Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis

In patients with pulmonary hypertension, the mortality rate associated with COVID-19 has declined sharply with the emergence of the Omicron variants https://bit.ly/42OMsf

Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc

Pulmonary Hypertension in Patients With COPD : Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)

Funding Information: FUNDING/SUPPORT: This work was supported by the German Center of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: C. D. V. has received fees for serving as a speaker, consultant, and an advisory board member from the following companies: Acceleron, Actelion, Bayer, Dompè, GSK, Janssen, MSD, Pfizer, and United Therapeutics. M. M. H. has received speaker fees, honoraria, or both for consultations from Acceleron, Actelion, Bayer, Janssen, MSD, and Pfizer. D. H. has received travel compensation from Actelion, Boehringer-Ingelheim, and Shire. D. P. has received fees for consultations from Actelion, Aspen, Biogen, Bayer, Boehringer Ingelheim, Johnson & Johnson, Novartis, Daiichi Sankyo, Sanofi, and Pfizer. N. B. received speaker fees from Bayer/MSD and Actelion/Janssen. K. M. O. has received speaker fees from Actelion, Bayer, and Lilly. H. A. G. has received honorariums for consultations, speaking at conferences, or both from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is member of advisory boards for Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He also has received governmental grants from the German Research Foundation (DFG), Excellence Cluster Cardiopulmonary Research (ECCPS), State Government of Hessen (LOEWE), and the German Ministry for Education and Research (BMBF). M. Held has received speaker fees and honoraria for consultations from Actelion, Bayer, Boehringer Ingelheim Pharma, Encysive, Glaxo Smith Kline, Lilly, Janssen, Novartis, Pfizer, Nycomed, Roche, and Servier. H. K. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics and research grants from Actelion. T. J. L. has received speaker fees, honoraria for consultations, and research funding from Actelion, Acceleron Pharma, Bayer, GSK, Janssen-Cilag, MSD, and Pfizer. S. R. has received honoraria for lectures, consultancy, or both from Actavis, Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics. D. D. declares honoraria for lectures, consultancy, or both from Actelion, Bayer, GSK, Novartis, Pfizer, and Servier; participation in clinical trials for Actelion, Bayer, GSK, and Novartis; and research support to his institution from Actelion. R. B. has received fees from GSK, UT, Dompè, Bayer, Ferrer, MSD, and AOP Orphan Pharmaceuticals. M. C. has received fees for consulting from GSK and speaker fees from Bayer and Pfizer. M. Halank has received speaker fees and/or honoraria for consultations from Acceleron, Actelion, AstraZeneca, Bayer, BayerChemie, GSK, Janssen, MSD and Novartis. A. V.-N. reports receiving lecture fees from Actelion, Bayer, GlaxoSmithKline, Lilly, and Pfizer; serves on the advisory board of Actelion and Bayer; and serves on steering committees for Actelion, Bayer, GlaxoSmithKline, and Pfizer. D. S. received fees for lectures, consulting, research support, or a combination thereof to his institution from Actelion, Bayer, GSK, and Pfizer. R. E. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics. J. S. R. G. has received speaker fees and honoraria for consultations from Acceleron, Actelion, Bayer, Complexa, GSK, MSD, Pfizer, and United Therapeutics. M. D. has received investigator, speaker, consultant, or steering committee member fees from Actelion, Aventis Pharmaceuticals, Bayer, Eli Lilly, Encysive, Gilead (Myogen), GlaxoSmithKline, Nippon Shyniaku, Novartis, Pfizer, Schering, and United Therapeutics; educational grants from Actelion, GlaxoSmithKline, Pfizer, and Therabel; and research grants from Actelion, Pfizer, and GlaxoSmithKline. She is holder of the Actelion Chair for Pulmonary Hypertension and of the GSK chair for research and education in pulmonary vascular pathology at the Catholic University of Leuven. J. C. has received fees for consultancies and lectures from Actelion, Bayer, GSK, United Therapeutics, and Pfizer as well as equipment and educational grants from Actelion. C. O. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, and Pfizer. H. K. has received honoraria for lectures, consultancy, or both from Actelion-Janssen, Amicus Therapeutics, and Bristol Meyers Squibb. O. D. has or had consultancy relationships, has received research funding (last 3 years), or both from AbbVie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Corpus, Drug Development International Ltd, CSL Behring, ChemomAb, Ergonex, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, Italfarmaco, iQone, iQvia, Kymera Therapeutics, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bio Science, and UCB in the area of potential treatments of scleroderma and its complications including PH. In addition, he has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143). E. G. has received honoraria for consultations, speaking at conferences, or both from Bayer/MSD, Actelion/Janssen, GWT-TUD, and OMT/United Therapeutics. None declared (A. S.). Publisher Copyright: © 2021 The AuthorsBackground: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Research Question: Which factors determine the outcome of PH in COPD? Study Design and Methods: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). Results: The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Interpretation: Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. Trial Registry: ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.govpublishersversionPeer reviewe

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

Funding Information: Marius M. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, MSD, and Pfizer. Nicola Benjamin has received fees for lectures and/or consultations from Actelion. Ekkehard Grünig has received fees for lectures and/or consultations from Actelion, Bayer, GSK, MSD, United Therapeutics, and Pfizer. Karen M. Olsson has received fees for lectures and/or consultations from Actelion, Bayer, United Therapeutics, GSK, and Pfizer. C. Dario Vizza has received fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics Europe. Anton Vonk-Noordegraaf has received fees for lectures and/or consultation from Actelion, Bayer, GSK, and MSD. Oliver Distler has/had a consultancy relationship with and/or has received research funding from 4-D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemoAb, EpiPharm, Ergonex, espeRare foundation, GSK, Genentech/Roche, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm, and Sinoxa in the area of potential treatments of scleroderma and its complications including pulmonary arterial hypertension. In addition, Prof Distler has a patent for mir-29 for the treatment of systemic sclerosis licensed. Christian Opitz has received fees from Actelion, Bayer, GSK, Pfizer, and Novartis. J. Simon R. Gibbs has received fees for lectures and/or consultations from Actelion, Bayer, Bellerophon, GSK, MSD, and Pfizer. Marion Delcroix has received fees from Actelion, Bayer, GSK, and MSD. H. Ardeschir Ghofrani has received fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer, and United Therapeutics. Doerte Huscher has received fees for lectures and consultations from Actelion. David Pittrow has received fees for consultations from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi. Stephan Rosenkranz has received fees for lectures and/or consultations from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics. Martin Claussen reports honoraria for lectures from Boehringer Ingelheim Pharma GmbH and Roche Pharma and for serving on advisory boards from Boehringer Ingelheim, outside the submitted work. Heinrike Wilkens reports personal fees from Boehringer and Roche during the conduct of the study and personal fees from Bayer, Biotest, Actelion, GSK, and Pfizer outside the submitted work. Juergen Behr received grants from Boehringer Ingelheim and personal fees for consultation or lectures from Actelion, Bayer, Boehringer Ingelheim, and Roche. Hubert Wirtz reports personal fees from Boehringer Ingelheim and Roche outside the submitted work. Hening Gall reports personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics outside the submitted work. Elena Pfeuffer-Jovic reports personal fees from Actelion, Boehringer Ingelheim, Novartis, and OMT outside the submitted work. Laura Scelsi reports personal fees from Actelion, Bayer, and MSD outside the submitted work. Siliva Ulrich reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, and grants and personal fees from Actelion SA/Johnson & Johnson Switzerland and MSD Switzerland outside the submitted work. The remaining authors have no conflicts of interest to disclose. Funding Information: This work was supported by the German Centre of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . These companies were not involved in data analysis or the writing of this manuscript. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.publishersversionPeer reviewe

COMPERA 2.0: A refined 4-strata risk assessment model for pulmonary arterial hypertension

BACKGROUND Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a 3-strata model to categorise risk as low, intermediate, or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on 4 risk categories with intermediate risk subdivided into intermediate-low and intermediate-high risk. METHODS We analysed data from COMPERA, a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on functional class (FC), 6 min walking distance (6 MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal fragment of pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed with Kaplan-Meier analyses, log-rank testing, and Cox proportional hazards models. RESULTS Data from 1,655 patients with PAH were analysed. Using the 3-strata model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined 4-strata risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the 3-strata model and in 49.2% with the 4-strata model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk. CONCLUSIONS Modified risk stratification using a 4-strata model based on refined cut-off levels for FC, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original 3-strata model

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis

BACKGROUND The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. METHODS Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. RESULTS All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. CONCLUSION While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials

Temporal trends in pulmonary arterial hypertension: Results from the COMPERA registry

BACKGROUND: Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extend this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival. METHODS: We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we look at annualized data and at cumulated data comparing the periods 2010-2014 and 2015-2019. RESULTS: A total of 2,531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010-2014 and 2015-2019 periods, 1-year survival estimates were similar (89.0% [95% CI, 87.2%, 90.9%] and 90.8% [95% CI, 89.3%, 92.4%]), respectively, whereas there was a slight but non-significant improvement in 3-year survival estimates (67.8% [95% CI, 65.0%, 70.8%] and 70.5% [95% CI, 67.8%, 73.4%]), respectively. CONCLUSIONS: The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed

Pulmonary vascular resistance predicts mortality in patients with pulmonary hypertension associated with interstitial lung disease: results from the COMPERA registry

In patients with pulmonary hypertension associated with interstitial lung disease, pulmonary vascular resistance provides stronger prognostic information than mean pulmonary arterial pressure https://bit.ly/3w1QcI