Objective Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants. Methods Overall, 502 AS patients were examined, consisting of 312 who had first-degree relatives (FDR) with AS (familial) and 190 who had no FDR with AS or spondyloarthritis (sporadic). All patients and affected FDRs fulfilled the modified New York Criteria for AS. The patients were recruited from two U.S. cohorts (NASC and PSOAS) and from the United Kingdom- Oxford cohort. The frequencies of AS susceptibility loci in IL23R, IL1R2, ANTRX2, ERAP1, two intergenic regions on chromosomes 2p15 and 21q22, and HLA-B27 status as determined by the tag SNP rs4349859 were compared between familial and sporadic cases. Association between SNPs and multiplex status was assessed by logistic regression controlling for sibship size. Results HLA-B27 was significantly more prevalent in familial than sporadic cases of AS (p=0.0001, OR: 4.44, CI: (2.06–9.55)). Furthermore, the AS risk allele at chromosome 21q22 intergenic region showed a trend towards higher frequency in the multiplex cases (p=0.08). The frequency of the other AS risk variants did not differ significantly between familial and sporadic cases, either individually or combined. Conclusions HLA-B27 is more prevalent in familial than sporadic cases of AS, demonstrating higher familial aggregation of AS in patients with HLA-B27 positivity. The frequency of the recently described non-MHC susceptibility loci is not markedly different between the sporadic and familial cases of AS.
Introduction Secukinumab is a fully human anti-interleukin 17A monoclonal antibody approved for the treatment of psoriatic arthritis (PsA) in the United States. Few studies have investigated prescribing patterns among rheumatologists who have initiated secukinumab for the treatment of patients with PsA in real-world settings. This US medical chart review describes clinical and treatment characteristics of patients with psoriatic arthritis (PsA) who were prescribed secukinumab and rheumatologist-reported reasons for prescribing secukinumab in clinical practice. Methods This US medical chart review included patients with physician-diagnosed PsA aged ≥ 18 years initiating secukinumab after January 15, 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, comorbidity profiles, and treatment histories before or on the date of the first secukinumab prescription recorded in the medical chart. Information on reasons for secukinumab prescription and dosing was also collected. Results Medical charts from 153 patients with PsA who initiated secukinumab were reviewed by 46 rheumatologists between July 7, 2017, and August 11, 2017. Overall, 53.6% of patients were male, mean (standard deviation) age was 47.3 (11.5) years, and 24.8% were biologic naive. The most common reasons for secukinumab prescription among biologic-naive and biologic-experienced patients, respectively, were efficacy/effectiveness of secukinumab (84.2%) and failure of other prior biologics (80.9%). Nearly all patients (94.1%) received a loading regimen, including 150 mg every week (32.7%) and 300 mg every week (61.4%). Overall, 145 patients (94.8%) received ≥ 1 maintenance dose, of whom 49.7% received 150 mg every 4 weeks and 50.3% received 300 mg every 4 weeks. Conclusions At the time of the chart review, most patients with PsA who initiated secukinumab were biologic experienced, although one-quarter received secukinumab as first-line biologic therapy. Efficacy/effectiveness of secukinumab and failure of other biologics were the most common reasons for initiating secukinumab. Funding Novartis Pharmaceuticals Corporation, East Hanover, NJ. Plain Language Summary Plain language summary available for this article.
ObjectivesTo characterize US patients with ankylosing spondylitis (AS) who were treated with secukinumab and to assess rheumatologist-reported reasons for prescribing treatment in clinical practice.MethodsThis descriptive analysis of data from a US retrospective medical chart review included patients aged ≥ 18 years diagnosed with AS who initiated secukinumab after 15 January 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, co-morbidity profile, and treatment history prior to or on the index date, defined as the date of the first secukinumab prescription recorded in the medical chart. Information on physician-level characteristics and reasons for secukinumab prescription and dosing were also collected.ResultsMedical charts from 78 patients with AS who initiated secukinumab were reviewed by 25 rheumatologists between 7 July 2017 and 11 August 2017. Overall, 76.9% of patients were male, mean (SD) age was 39.8 (10.8) years, and 34.6% were biologic naïve. The most common reasons for secukinumab initiation among biologic-naïve and biologic-experienced patients, respectively, were efficacy/effectiveness (77.8%) and failure of other prior biologics (84.3%). Nearly all patients (94.9%) received a loading dose, including 150 mg every week (39.7%), 300 mg every week (53.8%), and other (1.3%). Overall, 73 patients (93.6%) received ≥ 1 maintenance secukinumab dose, of whom 56.2% and 43.8% received 150 mg and 300 mg, respectively, every 4 weeks.ConclusionsIn this US medical chart review of patients with AS who initiated secukinumab, approximately one-third were biologic naïve, and secukinumab efficacy/effectiveness and failure of other biologics were the most common reasons for initiating secukinumab.Electronic supplementary materialThe online version of this article (10.1007/s40801-018-0146-9) contains supplementary material, which is available to authorized users.
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