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Objectives: Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR)., Methods: Observational case-control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared., Results: From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001)., Conclusions: We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality., Competing Interests: Competing interests: JARI has received support for research grants or contracts from BMS. ET-A has received payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, and support for attending meetings from Boehringer Ingelheim, Nordic Pharma and Merck Sharp & Dohme. JF-M has received payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Amgen, Lilly, Galápagos, Boehringer Ingelheim, Novartis and also support for attending meetings from Boehringer Ingelheim. LS-F has received payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, BMS, Lilly, support for attending meetings from Pfizer, Lilly and Novartis and also has participated on Data Safety Monitoring Board or Advisory Board for Novartis, Merck Sharp & Dohme and Sanofi. BS has received consulting fees from Boehringer Ingelheim, payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche and Boehriner Ingelheim, support for attending meetings from Boehringer Ingelheim, Roche and AstraZeneca. JLA has received consulting fees from AbbVie, Amgen, AstraZeneca, Biogen, Cellgene, Celltion, Fresenius-Kabi, Galápagos, Gebro, GSK, Merck Sharp & Dohme, Pfizer, Regeneron, UCB, payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Antares, Biogen, GSK, Janssen, Merck Sharp & Dohme, Lilly, Nordic, Novartis, Sanofi, UCB and also support for attendings from AbbVie, Gebro, Janssen, Merck Sharp & Dohme, Nordic, Novartis and Pfizer. EB has received payment honoraria for educational events from Boehringer Ingelheim, support for attending meetings and/or travel from Boehringer Ingelheim and Janssen. DB currently works at Savana Research, has received grants or contracts from Novartis, payment honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen and AbbVie, support for attending meetings from UCB, Novartis and AbbVie. DV works at BMS Company and own stocks as BMS employee. SLV works at BMS Company and own stocks as BMS employee. RACM works at BMS Company. The present manuscript was fully supported by Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach., Methods: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry., Results: In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]., Conclusions: SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Interleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA., Methods: IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase., Results: In the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5)., Conclusions: Genetic variation at IL6R gene is associated with joint damage in RA.