Epidemiology, treatment patterns, clinical outcomes, and disease burden among patients with immune-mediated thrombotic thrombocytopenic purpura in the United States

Abstract

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy. Due to its rarity, epidemiology and real-world outcomes data are scarce.

Objectives: The aim was to assess epidemiology, treatment patterns, clinical outcomes, and disease burden in patients with iTTP in the United States.

Methods: This longitudinal, retrospective observational study of the Optum-Humedica database included patients with an iTTP diagnosis (≥1 documented ADAMTS13 activity less than 10% or one or more iTTP episodes) from January 2007 to December 2019.

Results: Of 666 patients with an iTTP diagnosis between October 2015 and December 2019, 302 (45%) had one or more iTTP episodes. The pooled annual incidence of documented iTTP during this period was 3.43/million, and the annual incidence of one or more iTTP episodes was 1.81/million. Patients with one or more iTTP episodes received a median of six therapeutic plasma exchange (TPE) sessions per episode; 86% received corticosteroids, and 59% received rituximab. Exacerbations occurred in 17% (52/302) and relapse in 11% (34/302); 34% (103/302) had one or more thromboembolic events. Mortality rates during the study period were 25% (167/666) among all patients with iTTP diagnosis, and 14% (41/302) among patients with one or more iTTP episodes. In the assessment of disease burden (January 2007 to September 2019), patients in the iTTP cohort (n = 514) presented with a mean of 14 comorbidities, compared with 3 in a matched non-iTTP cohort (n = 2570). In a cluster analysis, duration of iTTP episode and mortality rate were greater in older versus younger patients.

Conclusions: Despite treatment with TPE and immunosuppressants, patients with iTTP have high risk of morbidity and mortality, demonstrating the need for more effective therapies.

Keywords: blood platelets; epidemiology; morbidity; thrombotic microangiopathies; thrombotic thrombocytopenic purpura.

FIGURE 1

Study design. Study periods were October 2015–December 2019 (Objectives 1 and 2) and January 2007–September 2019 (Objective 3). ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange.

FIGURE 2

Patient flow through the study for Objectives 1 and 2 (A) and Objective 3 (B). ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; EHR, electronic health record; HIV, human immunodeficiency virus; HUS, hemolytic uremic syndrome; iTTP, immune‐mediated thrombotic thrombocytopenic purpura; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange. ^aHUS, systemic infection, Rocky Mountain spotted fever, aspergillosis infection, Escherichia coli infection, or hypertensive crisis during same hospitalization. ^bHIV, organ/stem cell transplant, malignancy, or systemic lupus erythematosus ≤6 months before or during same index hospitalization.

FIGURE 3

Comparison of comorbidities in the iTTP versus control cohort: (A) Prevalence of comorbidities and age of occurrence (ranked from earliest to latest) and (B) time difference between comorbidity occurrence and index date^a. ^aNegative values indicate onset prior to index date; positive values indicate onset after index date. CKD, chronic kidney disease; ECG, electrocardiogram; iTTP, acquired thrombotic thrombocytopenic purpura; MI, myocardial infarction; RD, renal disease; TIA, transient ischemic attack

FIGURE 4

Baseline demographic and clinical characteristics of patients with iTTP by cluster. CV, cardiovascular; iTTP, acquired thrombotic thrombocytopenic purpura; SD, standard deviation.