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Aims/hypothesis: Some studies find an increased risk of type 1 diabetes in children exposed to antibiotics. We investigated if exposure to antibiotics increases the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes., Methods: We used data from a Swedish case-control study (Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes [ESTRID]: LADA, n=597; type 2 diabetes, n=2065; control participants matched on participation time, n=2386) and a case-control study nested within the Norwegian Trøndelag Health Study (HUNT) (n=82/1279/2050). Anatomical Therapeutic Chemical (ATC) codes indicating antibiotic dispensations were retrieved from the Swedish National Prescribed Drug Register and Norwegian Prescription Database. Multivariable adjusted ORs with 95% CIs were estimated by conditional logistic regression and pooled using fixed-effects inverse-variance weighting., Results: We observed no increased risk of LADA with exposure to antibiotics up to 1 year (OR pooled 1.15, 95% CI 0.93, 1.41) or 1-5 years (OR pooled 0.98, 95% CI 0.80, 1.20) prior to diagnosis/matching for one or more vs no dispensation of any type of antibiotic. An increased risk was observed for one or more vs no dispensations of narrow-spectrum antibiotics, but not broad-spectrum antibiotics, 6-10 years prior to LADA diagnosis (OR pooled 1.39, 95% CI 1.01, 1.91), which was driven by the Swedish data. There was little evidence of an increased risk of type 2 diabetes associated with antibiotic exposure 1-10 years prior to diagnosis., Conclusions/interpretation: We found no evidence that exposure to broad-spectrum antibiotics up to 10 years prior to diagnosis increases the risk of LADA. There was some indication of increased LADA risk with exposure to narrow-spectrum antibiotics, which warrants further investigation., Competing Interests: Acknowledgements: We thank the participants in ESTRID and HUNT, as well as the administrative personnel, nurses and research team members. Data availability: The de-identified datasets generated and analysed in the current study are available from the corresponding author on reasonable request (ESTRID) and with permission of the HUNT study by applying to the HUNT study data access committee. Funding: The ESTRID study was funded by grants from the Swedish Research Council (2018-03035), Research Council for Health, Working Life and Welfare (FORTE, 2018-00337), Novo Nordisk Foundation (NNF19OC0057274) and Swedish Diabetes Foundation. The ANDIS study was financed by Swedish governmental funding of clinical research (ALF), the Faculty of Medicine at Lund University, the Swedish Research Council (project grant no. 2020-02191 and strategic research area grant no. 2009-1039 [EXODIAB]), the Swedish Foundation for Strategic Research (IRC15-0067 [LUDC-IRC]) and Vinnova Swelife. EA was also funded by the Novo Nordisk Foundation (grant no. NNF21OC0070457), the Crafoord Foundation, the Bo & Kerstin Hjelt Diabetes Foundation and the Albert Påhlsson Foundation. The Trøndelag Health Study (HUNT) is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, the Central Norway Regional Health Authority and the Norwegian Institute of Public Health. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: SC, MR and JE contributed to the conception and design of the work. EA, LA, JA, DDG, VG, EPS, TT and BOA contributed to the acquisition of data. JE performed the analyses. All authors contributed to the interpretation of data. JE drafted the article and all authors edited, reviewed and approved the final version to be published. JE is responsible for the integrity of this work as a whole., (© 2024. The Author(s).)

Aims: Personalised medicine in chronic complex diseases such as rheumatoid arthritis (RA) is within reach but requires international multi-stakeholder collaboration. We exemplify how national implementations of the General Data Protection Regulation (GDPR) have introduced administrative delays and created disincentives for data sharing and collaborative research., Methods: Our Danish/Swedish/Norwegian research collaboration (the 3-year NordForsk-funded "NORA" project) aims to develop a personalised medicine approach for the management of RA, built on the exploitation of unique existing data sources: longitudinal data from clinical rheumatology registries, research cohorts, nationwide health care registries, and biobank material from >20 sample collections. Data and results are shared and accessed remotely by collaborators at secure servers. New biomarker assays and patient-centric implementations of the results are to be explored, validated, and disseminated to patients and health care via the development of digital tools., Results: Following the advice of legal experts at the involved academic or public institutions and private companies, GDPR compliance resulted in >20 legal documents to govern the collaboration (consortium-, joint controller-, research collaboration-, data sharing-, and a series of unique two-way data processing-, and material transfer agreements). Lack of agreed-upon templates, policies, procedures, and a shortage of legal resources have caused considerable delays. Thus, our research consortium has spent more time ensuring GDPR compliance than on actual research activities., Conclusions: The current interpretation and implementation of the legal premises (rather than the GDPR per se) for research collaborations caused unnecessary barriers and delays. Our experiences call for Nordic trust-based code-of-conduct-like framework agreements, and for harmonisation of procedures and templates, lest the Nordic advantage in research be lost., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Bente Glintborg: research grants (paid to institution) from Pfizer, Sandoz, AbbVie, BMS. Chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies.Hilde Berner Hammer: honoraria and/or research grants from AbbVie, Lilly, UCB, Pizer and Novartis.Saedis Saevarsdottir: part-time employee of deCODE genetics.Johan Rönnelid: advisory board member for Thermo Fisher Scientific and Werfen/Inova.Isabel Gehring: employee of Thermo Fisher Scientific.Merete Lund Hetland: all the following has been paid to institutions (i.e. no personal income): study grants or contracts with AbbVie, Biogen, BMS, Celltrion, Eli Lilly; Janssen Biologics B.V., MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, UCB. Lectures or presentations: Pfizer, Medac, Sandoz. AdBoard: AbbVie. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis and UCB.Tue Kragstrup: speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, UCB, and AbbVie. Consultancy fees from Bristol-Myers Squibb, UCB, Gilead, and Eli Lilly. Research grants from Gilead. Co-founder and clinical developer in Aptol Pharma.Ellen-Margrethe Hauge: fees for speaking and/or consulting from Novartis, AbbVie, Sanofi, Sobi; research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie; travel expenses from Pfizer, Sobi, AbbVie. Has been principal investigator of studies by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo, Sanofi. None of the aforementioned undertakings relate to this manuscript.Johan Askling: Karolinska Institutet has entered into agreements with the following companies, with Johan Askling as principal investigator: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi.The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To estimate short-term risks of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) as a function of current RA disease activity including remission., Methods: Data from clinical visits of RA patients in Sweden (SE) and Norway (NO) between January 1st 2012 until December 31st 2020 were used. At each visit, patient's disease activity was assessed including remission status (measured with several metrics). Through linkage to national health and death registers, patients were followed up for incident ACS up to six months from each visit. We compared the short-term risk of ACS in patients not in remission vs. in remission using Cox regression analyses with robust standard errors, adjusted for country and covariates (e.g., age, sex, prednisolone use, comorbidities). We also explored disease activity categories as exposure., Results: We included 212,493 visits (10,444 from Norway and 202,049 from Sweden) among 41,250 patients (72% women, mean age at visit 62 years). During the 6-month follow-ups, we observed 524 incident ACS events. Compared to patients in remission, patients currently not in remission had an increased rate of ACS: adjusted hazard ratio (95% confidence interval) 1.52 (1.24-1.85) with DAS28 metric. The crude absolute six-month risks were 0.2% for patients in remission vs. 0.4% for patients with DAS28 high disease activity. The use of alternative RA disease activity and remission metrics provided similar results., Conclusion: Failure to reach remission is associated with elevated short-term risks of ACS, underscoring the need for CV risk factor optimization in these patients., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes., Methods: We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment., Results: Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year., Conclusion: Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA., Competing Interests: Competing interests: SS is a part-time employee at deCODE genetics. E-MH has received institutional grants or contracts from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Rocke, Novartis or Abbvie, payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Sobi, support from attending meetings and/or travel from Pfizer, Sobi and Abbvie. participated on data safety monitoring board or advisory board for Novartis, Abbvie and Sanofi and is principal investigator in trials by SynACT Pharma, site principal investigator in trials by AbbVie, Novartis, Novo and Sanofi. HBH has received honoraria for lectures from AbbVie, Novartis, Lilly and UCB, and participated on advisory board for AbbVie, UCB and Novarties. Karolinska Institutet has entered into agreements with the following companies, with JA as PI: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi. BG has received research grant from Pfizer, AbbVie, BMS and Sandoz. The remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries., Methods: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment., Results: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association., Conclusion: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)