Mortality and causes of death across the systemic connective tissue diseases and the primary systemic vasculitides.

Objectives: Studies assessing relative mortality risks across the spectrum of systemic inflammatory rheumatic diseases are largely missing. In this study, we wanted to estimate standard mortality ratios (SMRs) and causes of death in an ethnically homogeneous cohort covering all major CTDs and primary systemic vasculitides (PSVs). Methods: We prospectively followed all incident CTD and PSV cases included in the Norwegian CTD and vasculitis registry (NOSVAR) between 1999 and 2015. Fifteen controls for each patient matched for sex and age were randomly drawn from the Norwegian National Population Registry. Causes of death were obtained from the National Cause of Death Register, death certificates and hospital charts. Results: The cohort included 2140 patients (1534 with CTD, 606 with PSV). During a mean follow-up time of 9 years, 279 of the patients (13%) died, compared with 2864 of 32 086 (9%) controls (P < 0.001). Ten years after diagnosis, the lowest survival was 60% in dcSSc, 73% in anti-synthetase syndrome (ASS) and 75% in lcSSc. In the CTD group, the highest SMRs were observed in dcSSc (SMR 5.8) and ASS (SMR 4.1). In the PSV group, Takayasu arteritis (SMR 2.5) and ANCA-associated vasculitis (SMR 1.5) had the highest SMRs. Major causes of death were cardiovascular disease (CTD 27%, PSV 28%), neoplasms (CTD 25%, PSV 27%), chronic respiratory disease (CTD 20%, PSV10%) and infections (CTD 9%, PSV 16%). Conclusion: We observed premature deaths across the spectrum of CTDs and PSVs, with highest SMRs in dcSSc and ASS. The overall mortality was highest in the CTD group.

TNF inhibitors appear to inhibit disease progression and improve outcome in Takayasu arteritis; an observational, population-based time trend study.

BACKGROUND: Magnetic resonance imaging (MRI) and computed tomography (CT) angiography have now largely replaced interventional angiography in the diagnoses and follow up of Takayasu arteritis (TAK) but data on the effects of this change of imaging method on diagnostic delay and vascular damage, and detailed data on the effect of different treatment regimens on the accumulation of vascular damage are missing. The aim of this study was to assess time trends in diagnostic delay, therapeutic approaches, arterial lesion accrual, persistent disease activity and remission rates in TAK. METHODS: The study cohort included all 78 patients from the 1999 - 2012 population-based South-East Norway TAK cohort and 19 patients from a tertiary referral cohort. TAK was classified by the 1990 American College of Rheumatology criteria and/or the 1995 modified Ishikawa diagnostic criteria. Data were retrieved by review of electronic patient journals and imaging data analyses. RESULTS: Diagnostic delay fell significantly during the study period and the number of lesions at diagnoses fell from three to two. Patients diagnosed from 2000 onwards more often received up-front treatment with disease-modifying antirheumatic drugs (DMARDs) than those diagnosed before 2000 (51% vs 4%; p < 0.01), and they were more often treated with TNF inhibitors during the disease course (44% vs 14%). During the first 2 years after initiation of therapy, 10% (3/32) of TNF-inhibitor-treated patients developed new lesions, compared to 40% (16/40) on DMARD treatment (OR 0.13) and 92% (14/15) on prednisolone monotherapy (OR 0.02). Patients on TNF inhibitors had a higher sustained remission rate than patients on DMARDs (42% vs 20%; p = 0.03). From 2000 onwards, the proportion of patients without new arterial lesions during the first 5 years after diagnosis increased from 29% in the patients diagnosed in 2000-2004, to 39% in 2005-2009 and 59% of patients diagnosed in 2010-2012. CONCLUSION: Our observational data indicate that more aggressive use of TNF inhibitors and DMARDs improve the outcome in TAK, but damage accrual is a continuous challenge and sustained remission is still relatively rare.

Prevalence, Incidence, and Disease Characteristics of Takayasu Arteritis by Ethnic Background: Data From a Large, Population-Based Cohort Resident in Southern Norway.

OBJECTIVE: To study the epidemiology and clinical characteristics of Takayasu arteritis (TAK) in southeast Norway (population 2.8 million). METHODS: All study area hospital databases were screened to capture every potential TAK case between 1999 and 2012. These cases were manually chart reviewed, and only patients fulfilling either the 1990 American College of Rheumatology classification or the 1995 Ishikawa diagnostic criteria were included. RESULTS: Inclusion criteria were met by 78 patients (68 female, 10 male). Point prevalence (by 2012) segregated by ethnic origin was 22.0 per 106 (95% confidence interval [95% CI] 17-29) in northern Europeans compared to 78.1 (95% CI 38-152) in Asian whites and 108.3 (95% CI 46-254) in Africans (P < 0.001). The incidence rate increased from 1 to 2 per 106 in the first to last 5-year period of the study (P = 0.03). Northern Europeans were mean age 32.3 years at onset, and 47% had involvement confined to aortic arch branches (angiographic type I), while 24% had extensive type V disease. Mean onset age in Asian and African cases was 20.3 years and 47% had type V disease. Coexisting inflammatory bowel disease was observed in 8% and ankylosing spondylitis in 7%. CONCLUSION: We report 2-4 times higher population prevalence than previously observed, and the highest prevalence ever found in Norwegians of Asian and African descent. The results support the idea that TAK in northern Europeans is marked by limited arterial involvement and older age at onset.

Takayasu Arteritis and Pregnancy: A Population-Based Study on Outcomes and Mother/Child-Related Concerns.

OBJECTIVE: To assess pregnancy outcomes in an unselected Takayasu arteritis (TAK) cohort, and identify pregnancy-related concerns. METHODS: Consenting female patients with TAK were predominantly recruited from a population-based southeast Norway TAK cohort. Additional cases (n = 8) were recruited at Oslo University Hospital. Data on the number of pregnancies, births, and pregnancy outcomes before and after disease onset were retrieved from medical charts, patient questionnaires, and the Medical Birth Registry of Norway (MBRN). Data on pregnancy-related concerns were gathered from patient questionnaires. RESULTS: Altogether, the 58 women in the TAK study cohort had been through 110 pregnancies, 73 (in 33 patients) before disease onset and 37 (in 23 patients) after onset. The frequencies of miscarriages, induced abortions, and maternal complications did not differ between pregnancies occurring before and after TAK onset. Pregnancy-related hypertension was seen in 4.2% of the patients, compared to 1.5% (P = 0.37) in the reference cohort from MBRN, and preeclampsia/eclampsia in 4.5% compared to 3% (P = 0.2). The mean gestational age at delivery in pregnancies after TAK onset was 37.5 weeks, compared to 39.5 weeks in the MBRN references (P < 0.001). Cesarean sections were more frequent in deliveries after TAK onset (42%) than in MRBN controls (11%) (P < 0.001). Pregnancy-related concerns were recorded in 80% of the TAK cohort, with 60% expressing concerns about passing the disease to offspring. CONCLUSION: In this population-based TAK cohort, the maternal and fetal outcomes were favorable. This study reveals a high prevalence of pregnancy-related concerns in TAK patients.