SUMMARY OF THE STORY
Why this website?
In February 2019, Drs. Brenda Gallie and Nancy Olivieri published a paper. A short summary of the findings from that paper is below. Read the paper here.
Iron Chelating Therapy, 2005-2019
Iron overload resulting from blood transfusions is potentially fatal. Early Toronto trials of a drug, deferiprone, were prematurely terminated by Apotex in 1996 after Dr. Nancy Olivieri raised safety concerns. This led to an extensive public controversy. In 2005 a different drug, deferasirox (Exjade®; Novartis) was approved by both the US Food and Drug Administration (FDA) and Health Canada as “first-line” treatment for iron overload. In 2009, the FDA refused approval of deferiprone (Ferriprox®; Apotex). In 2011, the FDA agreed to license deferiprone as “last resort” therapy: that is, to be prescribed only if first-line drugs had failed.
The 2019 findings of Drs. Gallie and Olivieri
Between 2012 and 2018, under an IRB-approved study, Drs. Gallie and Olivieri retrospectively inspected the records of patients treated with deferiprone or deferasirox at The University Health Network (UHN) Toronto. The paper reports (read here) that although up to 2015, deferiprone was unlicensed in Canada, 41 locally-transfused UHN patients were switched from first-line licensed therapies (deferoxamine or deferasirox) to unlicensed deferiprone. In deferiprone-exposed patients, body iron increased (worsened). By 2015, body iron exceeded the threshold for fatal complications in 50% deferiprone-exposed patients. During deferiprone exposure, new diabetes mellitus was diagnosed in 17% of patients, and liver dysfunction was diagnosed in 65% of patients. One patient died after 13 months of deferiprone exposure. (During deferasirox exposure, average body iron improved to optimal levels, and liver enzymes did not change).
Conclusions
“Deferiprone showed ineffectiveness and significant toxicity in most patients. Combination with low doses of first-line therapies did not improve the effectiveness of deferiprone. Exposure to deferiprone, over six years while the drug was unlicensed, in the face of ineffectiveness and serious toxicities, demands review of the standards of local medical practice. The limited scope of regulatory approval of deferiprone, worldwide, should restrict its exposure to the few patients genuinely unable to tolerate the two effective, first-line therapies.” Read the paper here.
Another study (2019)
Another, subsequent paper by the doctors of the UHN Red Cell Disorders Program (read here) reported that a total of 71 (not 41) patients were switched from first-line licensed therapies (deferoxamine or deferasirox) to unlicensed deferiprone between 2009 and 2015. In that paper, a second death amongst deferiprone-exposed patients was reported.
What Did These 71 Patients Know?
After publication, there was an assurance by the CEO at UHN of a Review of practices in the Red Cell Disorders program where switching from licensed therapy to unlicensed deferiprone had occurred over six years. This website is a chronology of correspondence on these issues.
Public statements by The University Health Network
“Being accountable to our patients and community is essential to maintaining public trust and an international reputation for excellence. At UHN, accountability means making the right clinical and managerial decisions, managing resources efficiently, and measuring our performance against provincial and national benchmarks.” See link here.
“Safe patient care is fundamental to quality health care services. At UHN, we are dedicated to delivering safe, patient centred care in an integrated care delivery environment. Improving patient safety is about creating an environment that is transparent and committed to quality improvement change.” See link here.