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Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry.

ABSTRACT: BACKGROUND/PURPOSE: Early diagnosis of inflammatory rheumatic diseases is important in order to improve long-term outcome. We studied whether delay in diagnosis (time between onset of symptoms and establishment of diagnosis) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) changed from year 2000 to 2011. METHODS: Month and year of initial symptoms and diagnosis, gender, hospital, year of birth and date of first data entry were obtained for 13,721 patients with RA, PSA or AS who had been registered in the DANBIO registry. Time between symptom onset and diagnosis was modelled using generalised linear regression to predict the average duration for each calendar year of initial symptoms with adjustments for gender, year of birth and date of DANBIO entry. RESULTS: Patients with valid data (RA: 10,416 (73%); PSA: 1970 (68%); AS: 1335 (65%)) did not differ significantly from the whole DANBIO population, except more missing data in early years. The regression model showed that the mean duration from initial symptoms to diagnosis for RA, PSA and AS declined steadily from 30, 53 and 66 months (year 2000), respectively, to 3-4 months (year 2011). Sensitivity analyses including patients who were included after 2005, patients who had received biological treatment or had symptom onset less than 2 and 5 years prior to first entry into DANBIO showed similar results. CONCLUSION: Since the year 2000, a significant reduction in diagnostic delay was observed in this large cohort of patients with RA, PSA or AS, probably reflecting a stronger awareness of the importance of early diagnosis.

SUBMITTER: Sorensen J

PROVIDER: S-EPMC4345887 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry.

Sørensen Jan J Hetland Merete Lund ML

Annals of the rheumatic diseases 20140217 3

<h4>Background/purpose</h4>Early diagnosis of inflammatory rheumatic diseases is important in order to improve long-term outcome. We studied whether delay in diagnosis (time between onset of symptoms and establishment of diagnosis) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) changed from year 2000 to 2011.<h4>Methods</h4>Month and year of initial symptoms and diagnosis, gender, hospital, year of birth and date of first data entry were obt ...[more]

PMID: 24534758

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Project description:IntroductionThis article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.MethodsThis integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).ResultsMedian treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.ConclusionRates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.Trial registrationClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Project description:Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR,SERPNA1, PCSK6, DNAH9 to rheumatoid arthrities (RA) and ankylosing spondylitis (AS). We previously found that encoding genes of PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6 and DNAH9 could be associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We used illumina customer designed microarray to verify the above finding with an increased numbers of samples. Genotyping was performed using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina) to determine possible associations of genes encoding PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR, SERPNA1, PCSK6, DNAH9 to RA and AS. A case-control study was performed with 51 AS patients, 266 rheumatoid arthritis (RA) and 163 health controls. Tag single nucleotide polymorphisms (tag SNPs) across the above genes were determined by searching the HapMap database. The tag SNPs were selected on the basis of linkage disequilibrium patterns observed in the Han Chinese in Beijing (CHB) samples that were genotyped as a part of the International HapMap Project. Only SNPs with a minor allele frequency of greater than 5% with a pair-wise r2 ≥ 0.8 in the HapMap were considered. SNPs that were in exons and untranslated regions (UTR), as well as promoters and introns within 500 bp of exons were also selected. Candidate SNPs were submitted to Illumina for a design score. The Illumina Assay Design Tool filtered out SNPs that were not suitable for the Illumina platform. Finally, 382 SNPs with a design score of “1” were selected. 382 SNPs within PADI1, PADI2, PADI3, PADI4, PADI6, PRKD3, Gc, GLRX,CDSN, PSORS1C1, TXNDC5, CA1, bub3, SORBS1, VDR,SERPNA1, PCSK6, DNAH9 encoding genes were selected. Genotyping was performed using Illumina VeraCode microarray in a case-control study including 51 AS patients, 266 rheumatoid arthritis (RA) and 163 health controls We performed genotyping using a custom-designed Illumina 384-SNP VeraCode microarray (Illumina). Peripheral blood samples were collected from patients with RA (n=266, 183 female) and AS (n=51, 10 female). RA patients had a mean age of 51.7 years, while AS patients had a mean age of 35.9 years. A total of 163 (60 female) healthy individuals with a mean age of 48.0 years were blood donors. Blood samples were put into Monovette tubes containing 3.8% sodium citrate. The genotyping was conducted with the BeadXpress Reader using the Illumina VeraCode GoldenGate Assay kit. 500 ng of sample DNA were used per assay. Genotype clustering and calling were performed using BeadStudio software (Genomestudio V2010.2 Genotyping module V1.6) (Illumina). This work was completed at the Beijing Institute of Genomics.

Dataset Information

Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry.

Publications

Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry.

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