Flares persist despite preventive treatment in hereditary TTP, study finds
Some standard therapies for rare condition also carry notable risks
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While standard preventive treatments may reduce the risk of disease flares and organ damage in people with congenital thrombotic thrombocytopenic purpura (TTP), flare-ups can still occur among patients on prophylaxis, a new study notes.
Further, certain preventive therapies long used for treating the rare condition carry notable safety risks, according to the researchers.
These findings highlight the limitations seen, in particular, with preventive TTP treatments derived from plasma, the non-cell portion of blood. The researchers say the study results underscore a need for new therapeutic approaches for the hereditary bleeding disorder.
“In this multinational, retrospective, longitudinal cohort, individuals with [congenital] TTP experienced a sustained and substantial burden of disease and treatment despite long-term plasma-based [preventive therapies],” the researchers wrote, adding that their study “suggests that more effective treatments may be needed.”
The study, “Natural History and Treatment Outcomes of Congenital Thrombotic Thrombocytopenic Purpura: A Retrospective Longitudinal Cohort Study,” was published in JHEOR, fully the Journal of Health Economics and Outcomes Research. The work was funded by Takeda Development Center Americas, which employs six of the 11 study authors. Takeda markets an approved treatment for congenital TTR called Adzynma (ADAMTS13, recombinant-krhn).
TTP is a bleeding disorder marked by small clots forming in blood vessels. This can damage organs and deplete platelets, which are tiny cell fragments that help form clots. Low platelet levels, in turn, can lead to unusual bleeding and other symptoms. The condition is caused by a deficiency of ADAMTS13, an enzyme that normally helps regulate clotting.
In most cases, TTP develops due to an autoimmune reaction. Congenital TTP, abbreviated cTTP, is a genetic form of the disease in which mutations lead to reduced ADAMTS13 activity. This rare type is often marked by so-called acute TTP events — disease flares where platelet levels plummet.
Given its rarity, there’s little data on congenital TTP
Because cTTP is so rare, there isn’t much data on how the disease tends to progress over time. Seeking to learn more, the research team analyzed data from 78 people with the condition who received care at one of nine specialty centers across the U.S. and Europe between 2009 and 2017.
“The aim of this study was to address key knowledge gaps in the health impacts and real-world management of patients living with cTTP. … This information may help to inform therapeutic decision-making and identify priorities for future research,” the researchers wrote.
As a genetic disease, cTTP is present throughout a person’s entire life. For some patients, cTTP causes obvious problems during childhood — but it’s also common for the disease to go unnoticed until adulthood. Indeed, in this study, nearly three-quarters of patients were diagnosed as adults.
In particular, the researchers highlighted that many women with cTTP were diagnosed during or after pregnancy, which can trigger acute TTP events. Because an accurate diagnosis is key to guide appropriate treatment, the researchers noted that “late recognition of cTTP may lead to poor long-term health outcomes such as end-organ damage.”
Preventive treatment typically is plasma infusions
Treatment of cTTP usually relies on plasma infusions, in which plasma from donors is used to supply the body with a working version of the ADAMTS13 enzyme. These treatments may be given for prophylaxis, or as a preventive treatment, to reduce the risk of disease complications. About 60% of patients in this study received any prophylaxis with plasma-derived products, the researchers noted.
Over a mean follow-up period of more than eight years, about 70% of the patients altogether — 55 people — experienced at least one acute TTP event, the data showed. Overall, given that some patients experienced more than one event, a total of 92 events were recorded.
The vast majority of these events — 85% or 80 episodes — occurred in patients who were not on prophylaxis, the data showed.
“The incidence [occurrence] of acute TTP events appeared lower during periods of prophylaxis than during periods without prophylaxis,” the researchers wrote.
Most of the acute TTP events resolved without complications, the team noted. However, some led to short-term complications or long-term organ damage, and two were ultimately fatal. The team noted that none of the attacks that occurred in patients on prophylaxis led to long-term organ damage, though they stressed that these results “should be interpreted with caution due to the small number of patients who underwent annual organ assessments during follow-up.”
The researchers noted that plasma-based prophylaxis was shown to help reduce disease activity. Still, most patients on preventive therapies had to stop or pause treatment due to side effects or lack of effectiveness, the team noted.
Our findings … [highlight] the limitations of [plasma-based treatment] in preventing ongoing manifestations, cumulative organ damage, and the logistical and safety burdens associated with repeated plasma infusions.
Adzynma contains a purified recombinant (lab-made) version of the ADAMST13 enzyme. In an exploratory analysis, the researchers compared findings from certain patients in this study with data from a Phase 3 clinical trial (NCT03393975) that compared Adzynma with plasma-derived prophylaxis. The results broadly suggest that the recombinant therapy leads to better disease control and fewer safety issues, according to the researchers.
The team found that patients who received plasma-derived prophylaxis had similar outcomes to those given these standard treatments in the trial.
“Our findings are consistent with lower observed acute TTP event rates during periods of [plasma-based] prophylaxis, while also highlighting the limitations of [plasma-based treatment] in preventing ongoing manifestations, cumulative organ damage, and the logistical and safety burdens associated with repeated plasma infusions,” the team wrote.
