Five years after the first reports linking gadolinium-based MRI contrast agents to nephrogenic system fibrosis (NSF), separate presentations of post-marketing data from manufacturers and an independent prospective study supported by agencies in France have validated the low-risk status of the contrast agent Dotarem (Gd-DOTA). This is according to researchers presenting this week at ECR 2011 in Austria, Vienna.
As of last August, the latest data collection for nearly 9,936 of the 40,000 patients involved in a worldwide post-marketing study of Dotarem, there has been no suspicion of NSF in any of the 204 patients, including four children, who had severe renal impairment (the chief risk factor for NSF).
Most patients in this study received the contrast agent in Germany or France, said Francois Laurent of the University of Bordeaux, and indications for their scans were primarily to diagnose conditions in the central nervous system. One possible flaw in the analysis is that follow-up for NSF was carried out only at three months after MRI, although NSF has sometimes emerged as long as eight or nine months later. "This is a problem," he admitted, "but it's probably convenient in order not to have too many patients lost to follow up."
An analysis of all sources of data about adverse events from 1989 through last year, including spontaneous reporting and information from health agencies as well as clinical trials, revealed only 1,020 accounts of any kind of adverse event — a rate of merely 0.007 percent in a total of about 15 million administrations of Gd-DOTA, said Eric de Kerviler of the Public Assistance Hospital in Paris. Among all reports received through last month, only nine confirmed cases of NSF have emerged, all of them in patients with renal failure, occurring between one and 32 weeks after contrast MRI.
Perhaps a more conclusive vindication will come from the prospective multicenter FINEST study launched two years ago with the support of the French Drug Agency and the French Society of Radiology to analyze the prevalence and risk factors for NSF among patients on dialysis who have MRI. Analysis includes people who have both contrast-enhanced and non-contrast MRI, and involves any gadolinium-containing contrast agent, not just Dotarem. Interim results reported by Vincent Launay-Vacher leave little room to suspect that bad news will emerge when the analysis is complete.
Investigators rely on self-reported survey forms sent back to their department by any study subject who notices a dermatologic problem; physical examinations by a dermatologist and a nephrologist follow any such report. To date, the study has accrued 510 volunteers. Exactly half that number has returned survey forms. One revelation, noted Launary-Vacher, was that five of these patients received contrast agents that are contraindicated in Europe for patients on dialysis.
Among all of these patents, there have been only nine reports of dermatological events, 6 percent of them from patients who had contrast MRI and 2 percent from people not given a contrast agent. All of the lesions have been characterized by specialists, and all were skin reactions common among patients on dialysis. None were NSF.