Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. OBJECTIVES: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. METHODS: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. RESULTS: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. CONCLUSIONS: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained

Commonalities and differences in set-up and data collection across European spondyloarthritis registries : results from the EuroSpA collaboration

Funding Open access funding provided by Royal Library, Copenhagen University Library The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit the manuscript.Peer reviewedPublisher PD

Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors : Data from the EuroSpA collaboration

Correction: Volume 58, Article Number 152141 DOI: 10.1016/j.semarthrit.2022.152141 Published: FEB 2023Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97-0.98), men vs. women: 1.88 (1.60-2.22), current vs. non-smoking: 0.76 (0.63-0.91), HLA-B27 positive vs. negative: 1.51 (1.20-1.91), TNF start year 2015-2018 vs. 2009-2014: 1.24 (1.06-1.45), CRP > 10 vs.Peer reviewe

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF-inhibitor: results from 13 European registries.

OBJECTIVES In bio-naïve patients with Psoriatic arthritis (PsA) initiating a Tumour Necrosis Factor inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes, were defined as common predictors. RESULTS In the pooled cohort (n = 13 369), six-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6,954, n = 5,275 and n = 13 369, respectively). Baseline predictors of remission, moderate response and 12-month drug retention were identified, five common across all three outcomes. Odds ratios (95% confidence interval) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (10 vs ≤ 10 mg/l: 1.52 (1.22-1.89) and one mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION Baseline predictors of remission, response and adherence to TNFi were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalisable from the country- to disease-level

Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors: Data from the EuroSpA collaboration

ObjectivesIn patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries.MethodsBaseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data.ResultsThe consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectivelyConclusionCommon baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.</p

Analysing and reporting of observational data: a systematic review informing the EULAR points to consider when analysing and reporting comparative effectiveness research with observational data in rheumatology

Objectives: To evaluate the analysis and reporting of comparative effectiveness research with observational data in rheumatology, informing European Alliance of Associations for Rheumatology points to consider. Methods: We performed a systematic literature review searching Ovid MEDLINE for original articles comparing drug effectiveness in longitudinal observational studies, published in key rheumatology journals between 2008 and 2019. The extracted information focused on reporting and types of analyses. We evaluated if year of publication impacted results. Results: From 9969 abstracts reviewed, 211 articles fulfilled the inclusion criteria. Ten per cent of studies did not adjust for confounding factors. Some studies did not explain how they chose covariates for adjustment (9%), used bivariate screening (21%) and/or stepwise selection procedures (18%). Only 33% studies reported the number of patients lost to follow-up and 25% acknowledged attrition (drop-out or treatment cessation). To account for attrition, studies used non-responder imputation, followed by last observation carried forward (LOCF) and complete case (CC) analyses. Most studies did not report the number of missing data on covariates (83%), and when addressed, 49% used CC and 11% LOCF. Date of publication did not influence the results. Conclusion: Most studies did not acknowledge missing data and attrition, and a tenth did not adjust for any confounding factors. When attempting to account for them, several studies used methods which potentially increase bias (LOCF, CC analysis, bivariate screening…). This study shows that there is no improvement over the last decade, highlighting the need for recommendations for the assessment and reporting of comparative drug effectiveness in observational data in rheumatology