Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis: results from the nationwide registries DANBIO and ICEBIO.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care.We conducted an observational cohort study based on the nationwide Danish Rheumatologic Database (DANBIO) and Center for Rheumatology Research (ICEBIO) registries. Stratified by country, characteristics of patients treated with ≤3 mg infliximab/kg body weight, 3-5 mg/kg or ≥5 mg/kg every 8 weeks were described. Outcomes were evaluated by ACR 20%, 50% and 70% (ACR20/50/70) responses and European League Against Rheumatism good response after 6 months, disease activity after 12 months, Kaplan-Meier plots and regression analyses.Four hundred and sixty-two patients (376 Danish, 86 Icelandic) received treatment with infliximab. In Danish patients, the starting dose was ≤3 mg/kg in 110 patients (29%), 3-5 mg/kg in 157 (42%), ≥5 mg/kg in 38 (10%) and unregistered in 71 (19%). In Icelandic patients, corresponding numbers were 64 (74%), 17 (27%), 0 (0%) and 5 (6%). Patients with a higher body weight received lower doses per kilogram. Danish patients received higher doses than Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response

Treatment retention of infliximab and etanercept originators versus their corresponding biosimilars : Nordic collaborative observational study of 2334 biologics naive patients with spondyloarthritis

Objective Although clinical trials support equivalence of originator products and biosimilars for etanercept and infliximab, real-world studies among biologics-naive patients with spondyloarthritis (SpA) are lacking. The objectives were to compare treatment retention in biologics-naive patients with SpA starting either the originator product or a biosimilar of infliximab and etanercept, and to explore the baseline characteristics of these patients. Methods Patients with SpA (ankylosing spondylitis/non-radiographical axial SpA/undifferentiated SpA), starting infliximab or etanercept as their first-ever biological disease-modifying antirheumatic drug during January 2014-June 2017 were identified in five Nordic biologics-rheumatology registers. Baseline characteristics were retrieved from each registry; comorbidity data were identified through linkage to national health registers. Country-specific data were pooled, and data on infliximab and etanercept were analysed separately. Comparisons of treatment retention between originators and biosimilars were assessed through survival probability curves, retention rates (2 years for infliximab/1 year for etanercept) and Hazard Ratios (HR). Results We included 1319 patients starting infliximab (24% originator/76% biosimilar), and 1015 patients starting etanercept (49% originator/51% biosimilar). Baseline characteristics were largely similar for the patients treated with the originators compared with the corresponding biosimilars. Survival probability curves were highly similar for the originator and its biosimilar, as were retention rates: infliximab 2-year retention originator, 44% (95% CI 38% to 50%)/biosimilar, 46% (95% CI: 42% to 51%); and etanercept 1-year retention originator, 66% (95% CI 61% to 70%)/biosimilar, 73% (95% CI 68% to 78%). HRs were not statistically significant. Conclusion This observational study of biologics-naive patients with SpA from five Nordic countries showed similar baseline characteristics and very similar retention rates in patients treated with originators versus biosimilars, for both infliximab and etanercept, indicating comparable effectiveness in clinical practice.Peer reviewe

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

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 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

A strong familiality of ankylosing spondylitis through several generations

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To elucidate the familiality of ankylosing spondylitis (AS) in Iceland. METHODS: The Icelandic genealogy database and population-wide data on all living Icelanders diagnosed as having AS (n=280), who previously had taken part in an epidemiological study on the prevalence of AS in Iceland, were included in the study. Identification of all interpatient relationships in the genealogy database allowed calculation of estimates of the RR for AS in the first-degree relatives (FDRs) to fourth-degree relatives of patients. For each AS proband, 1000 sets of matched Icelandic subjects in the genealogy database were used as controls. RESULTS: FDRs, second-degree and third-degree relatives had RRs of 75.5, 20.2 and 3.5, respectively (all p values <0.0001), indicating a significantly increased risk for relatives of the patients with AS to develop AS, suggesting a strong heritable factor, while the fourth-degree relatives had a RR of 1.04 (p=0.476) for having AS. CONCLUSIONS: Patients with AS in Iceland are significantly more related to each other than to randomly sampled control subjects. This is in agreement with previous reports on the familiality of AS, but the present study has more power and extends over larger familiar cohorts than previously reported

Tatiana Riabouchinska as The Golden Cockerel (centre), and artists of the company, in Le coq d'or, Covent Garden Russian Ballet, Australian tour, His Majesty's Theatre, Melbourne, October 1938 (3) [picture] /

From: Le coq d'or (The golden cockerel) : ballet in three scenes / based on the fairy tale by Aleksandr Pushkin and the opera libretto by Vladimir Bielsky ; music by Nikolay Rimsky-Korsakoff, adapted by Nikolai Tcherepnine.; Inscription: "V16".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Choreography by Michel Fokine ; curtain, scenery and costumes by Nathalie Gontcharova ; scenery executed by Prince A. Schervachidze ; costumes executed by B. Karinska.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3992394. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-194040). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOBJECTIVE: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA). METHODS: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab 4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit). The Kruskal-Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. RESULTS: One hundred and eighty-five patients (61% female) were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS) pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP), numbers of swollen or tender joints, or Disease Activity Score (DAS) 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. CONCLUSION: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment.Icelandic Society for Rheumatolog

Prevalence and clinical characteristics of ankylosing spondylitis in Iceland - a nationwide study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVES: To determine the prevalence and clinical characteristics of ankylosing spondylitis (AS) in the Icelandic population, which carries a high prevalence of HLA-B27. METHODS: A nationwide search was performed by screening hospital records and private rheumatology services for cases of AS in association with an on-going genetic study. Individuals diagnosed with AS according to the modified New York criteria were asked to participate in the study by answering a standardised questionnaire and to undergo an interview and clinical evaluation. RESULTS: A total of 256 individuals fulfilled the modified New York classification criteria for AS (169 male, 87 female); 84% of these individuals were HLA-B27 positive vs. 15% in the population (p<10-16). Of those contacted 223 patients (87.1%) answered the standardised questionnaire and were included in the study. The prevalence of AS in Iceland was 0.13% (CI 0.11-0.14%). A highly conservative prevalence number, based only on clinically evaluated patients, gave prevalence of 0.10% (CI 0.09-0.11%). Mean age at onset of symptoms was 24+/-8 years and at diagnosis 32.1+/-10.2 for male and 34.2+/-10.1 for female patients (not significant). Female patients more often had arthritis in peripheral joints and male patients were more often diagnosed with iritis. Prostatitis was experienced by 27% of male patients. CONCLUSIONS: AS is less common in the Icelandic population than reported in various Caucasian populations with a similar prevalence of HLA-B27

Prevalence and clinical characteristics of ankylosing spondylitis in Iceland - a nationwide study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVES: To determine the prevalence and clinical characteristics of ankylosing spondylitis (AS) in the Icelandic population, which carries a high prevalence of HLA-B27. METHODS: A nationwide search was performed by screening hospital records and private rheumatology services for cases of AS in association with an on-going genetic study. Individuals diagnosed with AS according to the modified New York criteria were asked to participate in the study by answering a standardised questionnaire and to undergo an interview and clinical evaluation. RESULTS: A total of 256 individuals fulfilled the modified New York classification criteria for AS (169 male, 87 female); 84% of these individuals were HLA-B27 positive vs. 15% in the population (p<10-16). Of those contacted 223 patients (87.1%) answered the standardised questionnaire and were included in the study. The prevalence of AS in Iceland was 0.13% (CI 0.11-0.14%). A highly conservative prevalence number, based only on clinically evaluated patients, gave prevalence of 0.10% (CI 0.09-0.11%). Mean age at onset of symptoms was 24+/-8 years and at diagnosis 32.1+/-10.2 for male and 34.2+/-10.1 for female patients (not significant). Female patients more often had arthritis in peripheral joints and male patients were more often diagnosed with iritis. Prostatitis was experienced by 27% of male patients. CONCLUSIONS: AS is less common in the Icelandic population than reported in various Caucasian populations with a similar prevalence of HLA-B27