African ancestry linked to 50% higher iTTP relapse risk after rituximab
French researchers also find a patient's sex affects time until relapse
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Following rituximab treatment, people of African ancestry with immune thrombotic thrombocytopenic purpura (iTTP) experience a relapse significantly sooner than individuals with European ancestry, a study in France shows.
Further, the researchers found that iTTP patients with African ancestry have a 50% higher risk of relapse after receiving rituximab, an approved medication sometimes used off-label for treating those with the bleeding disorder.
In addition to African ancestry, being male and having experienced more relapses all increased the risk of new episodes, according to the findings of an analysis that used data from a large French registry.
“These results indicate that ethnicity affects [relapse-free survival] with patients of African ancestry relapsing earlier, suggesting that a closer ADAMTS13 monitoring might be necessary in high-risk patients,” the researchers wrote. TTP is characterized by a deficiency of the ADAMTS13 enzyme.
The study, “Ethnicity affects relapse-free survival in immune-mediated thrombotic thrombocytopenic purpura,” was published in the journal Haematologica.
TTP is characterized by the formation of blood clots in small blood vessels; this clots lead to organ damage. The disease is marked by reduced activity of ADAMTS13, an enzyme that normally prevents platelets from forming blood clots when they aren’t needed. In iTTP, self-reactive antibodies prevent the enzyme from working correctly.
Investigating rituximab responses in iTTP patients in France
Rituximab, an antibody-based therapy, may effectively prevent relapses in iTTP by reducing the number of B-cells, the immune cells that produce antibodies. However, treatment response may vary, with studies suggesting that African ancestry could be associated with decreased relapse-free survival, which is a commonly used measure of how long it takes before a relapse occurs.
Previous research on this topic has limitations, the researchers here noted — including that all studies to date have come from the U.S., “where medico-social factors may differ from those in other geographical regions and might influence access to regular diagnostic procedures, follow-up measurements (e.g. ADAMTS13 monitoring) and novel treatment options,” the investigators wrote.
To learn more, the international team of researchers turned to the French National TMA registry. The study was part of the Thrombotic Microangiopathy program (NCT00426686).
The team analyzed the role of ethnicity in iTTP relapse in 790 adults treated with rituximab as a preventive approach or for acute episodes.
“The French healthcare system provides universal coverage; therefore, social and economic factors might have a limited role compared to previous studies,” the team wrote.
Nearly three-quarter of the patients were women. The majority were of European ancestry (83%), while 17% were of African ancestry. Median follow-up was 41-47 months, or up to a maximum of nearly two years, in the two groups.
Ethnicity, being male shown to be key factors in relapse risk
ADAMTS13 response to treatment, defined as enzyme activity of at least 20%, was achieved by 96% of the patients following treatment with rituximab, regardless of ethnicity. The time to ADAMTS13 activity recovery following rituximab did not differ between people of European or African ancestry, the researchers noted.
However, following the first course of rituximab treatment, significantly fewer patients of African ancestry reached three years without a relapse compared with those of European ancestry, the data showed.
This measure tracked both clinical relapses, when symptoms worsen, and ADAMTS13 relapses, when the enzyme activity decreases.
Our findings provide robust confirmation of prior observations from US [study groups] suggesting ethnic disparities in [relapse-free survival] following rituximab in iTTP.
According to the researchers, these results highlight “that early therapeutic response is preserved, but durability of remission may be compromised in patients of African ancestry.”
Further analysis demonstrated that African ancestry was associated with a 50% higher risk of clinical or ADAMTS13 relapse. Being male increased that risk by 24%. A higher risk, by 61%, was also seen when treating a relapse rather than a first episode. This association persisted after adjusting for potential confounders, the team noted.
Independent of ethnicity, the risk of relapse increased with the number of disease episodes. After the first iTTP episode, 37% of patients relapsed. Those who had a first or second relapse experienced a further relapse in 46% and 59% of the cases, respectively.
In addition, the time to relapse shortened with the number of rituximab courses, “underscoring the cumulative burden of disease recurrence in relapsing patients,” the researchers wrote.
Overall, according to the team, “our findings provide robust confirmation of prior observations from US cohorts suggesting ethnic disparities in [relapse-free survival] following rituximab in iTTP. … We validate the association between African ancestry and increased relapse risk. ”
The researchers added that “these findings underscore the importance of integrating ethnicity into risk stratification models and support regular ADAMTS13 monitoring as a cornerstone of long-term management.”
