Race, rituximab, and relapse in TTP

Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Graphical abstract

Figure 1

Study cohort. A total of 645 participants in the USTMA Consortium iTTP Registry had a confirmed diagnosis with ADAMTS13 deficiency. An exacerbation was counted as a continuation of the iTTP episode that preceded it. We excluded episodes preceded by preemptive therapy (n = 17), patients lost to follow-up, and patients who received therapy other than corticosteroids or rituximab.

Figure 2

Risk factors for mortality in patients presenting with de novo or relapsed iTTP. A multivariate model of mortality from iTTP failed to demonstrate an effect of race on mortality. Minor edits made with Biorender.com.

Figure 3

Risk factors for iTTP relapse. A multivariate model of relapse identified race as the strongest predictor of relapse, along with a significant effect of previous relapse and a trend toward treatment with rituximab being protective against relapse. Minor edits made with Biorender.com. HR, hazard ratio.

Figure 4

Effect of race and rituximab therapy on RFS in patients presenting with de novo or relapsed iTTP. (A) Overall, Black patients had shorter time to relapse compared with White patients, regardless of treatment. (B) A wearing-off effect of rituximab was found in de novo iTTP, with Black patients seeming to lose the protective effect of rituximab faster than White patients. (C) A pronounced interaction between race and treatment was evident in relapsed iTTP episodes, where RFS more than doubled in White patients with the addition of rituximab. There was no difference in RFS in relapsed iTTP in Black patients, whether treated with rituximab or corticosteroids alone. Minor edits made with Biorender.com.

Figure 5

Treatment selection over time. The use of rituximab for treatment of iTTP increased steadily over time starting with its introduction in the early 2000s.