The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study

Introduction Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). Methods Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. Results C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r 2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r 2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). Conclusion CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs : results from four Nordic countries

Objectives To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator. Methods Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort. Results 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted. Conclusion The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.Peer reviewe

Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study) : Protocol for a Randomized, Controlled Open-Label Noninferiority Trial

Funding Information: The ReMonit study and the qualitative substudy received funding from the South-Eastern Norway Regional Health Authority (funding number 2021062) and the Centre for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway (funding number 328657).Peer reviewe

Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries

Objectives The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). Methods Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. Results Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaive) and 1948 with secukinumab (11% bionaive). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. Conclusion When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.Peer reviewe

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers : the Nordic example

RMD Open 2018;4:e000655. doi:10.1136/ rmdopen-2018-000655Peer reviewe

The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study

The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline.publishedVersio

Codon Size Reduction as the Origin of the Triplet Genetic Code

The genetic code appears to be optimized in its robustness to missense errors and frameshift errors. In addition, the genetic code is near-optimal in terms of its ability to carry information in addition to the sequences of encoded proteins. As evolution has no foresight, optimality of the modern genetic code suggests that it evolved from less optimal code variants. The length of codons in the genetic code is also optimal, as three is the minimal nucleotide combination that can encode the twenty standard amino acids. The apparent impossibility of transitions between codon sizes in a discontinuous manner during evolution has resulted in an unbending view that the genetic code was always triplet. Yet, recent experimental evidence on quadruplet decoding, as well as the discovery of organisms with ambiguous and dual decoding, suggest that the possibility of the evolution of triplet decoding from living systems with non-triplet decoding merits reconsideration and further exploration. To explore this possibility we designed a mathematical model of the evolution of primitive digital coding systems which can decode nucleotide sequences into protein sequences. These coding systems can evolve their nucleotide sequences via genetic events of Darwinian evolution, such as point-mutations. The replication rates of such coding systems depend on the accuracy of the generated protein sequences. Computer simulations based on our model show that decoding systems with codons of length greater than three spontaneously evolve into predominantly triplet decoding systems. Our findings suggest a plausible scenario for the evolution of the triplet genetic code in a continuous manner. This scenario suggests an explanation of how protein synthesis could be accomplished by means of long RNA-RNA interactions prior to the emergence of the complex decoding machinery, such as the ribosome, that is required for stabilization and discrimination of otherwise weak triplet codon-anticodon interactions

How does current disease activity in rheumatoid arthritis affect the short-term risk of acute coronary syndrome? : A clinical register based study from Sweden and Norway

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