Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n ؍ 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis. , previously known as nephrogenic fibrosing dermopathy, have been reported worldwide (1,2). The appearance of this new and serious disease has triggered considerable interest as to possible causative factors, including newly introduced clinical practices. However, until now, the eliciting factor(s) has not been identified. Mendoza et al. (3) recently reviewed the clinical picture of NSF. The typical patient is middle-aged and has ESRD. Most but not all are on regular dialysis treatment. The typical course begins with subacute swelling of distal parts of the extremities and is followed in subsequent weeks by severe skin induration and sometimes anatomic extension to involve thighs, antebrachium, and lower abdomen. The skin induration may be aggressive and associated with constant pain, muscle restlessness, and loss of skin flexibility. In some cases, NSF leads to serious physical disability, including wheelchair requirement. NSF initially was observed in and thought to affect solely the skin (thus the initial term nephrogenic fibrosing dermopathy), but more recent patient reports have demonstrated that several organs may be involved. Organ involvement may explain the suspected increased mortality of patients with NSF (3). There is no established treatment for NSF, but some cases have been reported to improve after kidney transplantation, and others seem to have been treated successfully with extracorporeal photopheresis (4).At the department of nephrology, Copenhagen University Hospital at Herlev, we became aware of a formerly unknown skin disease among our patients with ESRD during 2002 through 2005. Skin biopsies supported the clinical suspicion of NSF. Some of the case stories strongly indicated that the skin changes were elicited by contrast-enhanced magnetic resonance imaging (MRI). Since late 2001, we have used this method frequently for patients with ESRD, in particular for description of iliac and lower limb arteries before kidney transplantation (5). During the past 5 to 10 yr,...
Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality.Design, setting and subjects. We conducted a cohort study of the entire Danish population aged ‡18 years followed from 1997 to 2006 by individual-level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital-based treatment. Time-dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis.Main outcome measures. All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded.Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval [CI] 1.14-1.25) and 1.58 (95% CI 1.36-1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06-1.22) and 1.57 (95% CI1.27-1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis.Conclusions. Psoriasis is associated with increased risk of adverse cardiovascular events and all-cause mortality. Young age, severe skin affection and ⁄ or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.
Ustekinumab has a significantly longer drug survival than the anti-TNF-α agents. Switching from one biologic to another is associated with an impairment of drug survival. Preventing loss of efficacy is a major area of medical need in the biologic therapy of psoriasis and the strategies that improve drug survival should be further investigated.
SummaryBackground Adherence to treatment is an indicator of treatment success. Long-term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)-a inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERM-BIO covering patients with psoriasis treated with a biologic agent. All patients who received anti-TNF-a treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti-TNF-a agent and the previous response to an anti-TNF-a agent. In the group of anti-TNF-a-naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3AE70, 95% confidence interval (CI) 1AE99-6AE89] and etanercept (HR vs. infliximab 3AE18, 95% CI 1AE72-5AE86). The 4-year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti-TNF-a drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years of treatment.
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