Systematic Literature Review of the Economic and Quality of Life Burden of Congenital and Immune-Mediated Thrombotic Thrombocytopenic Purpura

Introduction

Thrombotic thrombocytopenic purpura (TTP) is an ultra-rare, life-threatening blood disorder characterized by fever, hemolytic anemia, and multi-organ involvement, particularly affecting the kidneys and brain.¹ Around 95% of TTP cases are immune-mediated (iTTP), and approximately 5% are congenital (cTTP). In both subtypes, symptoms are caused by reduced activity of the ADAMTS13 enzyme, resulting from the presence of autoantibodies against ADAMTS13 in iTTP, and inherited mutations in the ADAMTS13 gene in patients with cTTP. Severe ADAMTS13 deficiency results in the accumulation of ultra-large von Willebrand factor (VWF) multimers, leading to platelet consumption and microvascular thrombosis throughout the body.^2–4

Without appropriate treatment, patients with cTTP are at an increased risk of recurrent TTP events.⁵ During these events, patients are at risk of progressive organ damage and mortality if not appropriately managed.⁶ Traditional treatment approaches aim to restore ADAMTS13 activity through infusions of donor plasma, solvent/detergent blood plasma, or blood plasma-derived products such as intermediate purity factor VIII/VWF concentrates.^3,7 These plasma-based treatments may be administered on-demand to treat acute events, or prophylactically to prevent recurrences.^3,8 However, plasma-based treatments provide only incomplete and transient ADAMTS13 replacement, with plasma concentrations reaching only ~25% of normal levels and remaining at >10% of normal activity levels for only ~2 days after treatment.^9–11 Hence, disease progression often continues despite plasma-based treatments, leading to adverse clinical outcomes and long-term consequences, including fatigue, cognitive impairment, anxiety, depression, and impaired health-related quality of life (HRQoL).^12,13

Furthermore, both TTP and its treatment can have substantial personal and economic impacts. Patients with recurrent cTTP who are given prophylactic plasma-based treatments require frequent, time-consuming infusions. Acute events commonly result in unplanned healthcare resource utilization (HCRU), including hospitalizations, which contribute to reduced work productivity and increased healthcare costs.^14–17

To our knowledge, the overall burden of cTTP has not previously been characterized through a systematic literature review (SLR). This study aimed to address this gap by identifying and summarizing existing evidence on the burden associated with cTTP and its treatments, including economic evaluations of cTTP treatments, HCRU, associated costs, and utility and HRQoL outcomes in patients with cTTP. Given the rarity of cTTP and the resulting literature gap, studies reporting data on patients with iTTP and TTP of unspecified subtype were also considered to provide context on the potential economic and HRQoL burden of cTTP. This broader inclusion approach was justified by clinical similarities across TTP subtypes, enabling insights into the potential burden of cTTP where direct evidence was lacking.

Methods

Search Strategy and Sources

The SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁸ Three separate literature searches were conducted to identify studies reporting: 1) economic evaluations, 2) HCRU and cost, and 3) utility and HRQoL data in patients with cTTP. Following initial screening focused exclusively on cTTP, inclusion criteria were broadened for searches 1 and 3 to include studies reporting data on patients with iTTP or TTP of unspecified subtype due to limited availability of cTTP-specific data. Sufficient studies reporting HCRU and cost data in cTTP were available; hence, search 2 was restricted to studies including patients with cTTP only, and in cases where data for iTTP or TTP of unspecified subtype were also reported, only cTTP-specific data were extracted.

Electronic searches were conducted using the MEDical Literature Analysis and Retrieval System (MEDLINE) In-Process^®, MEDLINE^®, Excerpta Medica dataBASE^® (Embase), IN-Process, EconLit^TM, and the Centre for Reviews and Dissemination York databases (including the Health Technology Assessment Database, and the National Health Service [NHS] Economic Evaluation database). The search strategy aimed to identify studies including patients of any age with TTP (either cTTP, iTTP, or TTP of unspecified subtype), published at any time since database inception. Initial literature searches were conducted on September 28, 2021, and updated searches were performed on January 16, 2024.

Hand searches were also performed across health technology assessment (HTA) agency websites, relevant conference proceedings (2019–2024), and the bibliographies of identified SLRs, to capture any relevant records potentially missed in electronic searches. Full details of the sources used for the hand searches are shown in Supplementary Table 1.

Study Selection

All retrieved records were de-duplicated and screened for eligibility in two stages: first by title/abstract, and second at full text. Screening was conducted by two independent reviewers (DG and ISK), and any disagreements were resolved by a third, independent, non-author reviewer.

English-language records that included patients with cTTP, iTTP, or TTP without specifying disease subtype, which reported at least one of the following outcomes: economic evaluations, HCRU, costs, utility values or HRQoL, were retained and included in the SLR. No restrictions were applied to study interventions or comparators. Inclusion criteria are summarized in Table 1 and are shown in full in Supplementary Tables 2–4. The same eligibility criteria were used for both the initial and updated literature searches to ensure the inclusion of any suitable studies identified by the initial searches.

Table 1 Study Eligibility Criteria

Data Extraction and Data Synthesis

Data were extracted into a pre-designed grid by a single reviewer, with quality checks performed by a second reviewer and discrepancies resolved by a third, independent, non-author reviewer as needed. Multiple records from the same study were combined and treated as a single study.

Extracted data included study location, patient characteristics, study interventions and comparators, study design (including types of models used and underlying assumptions where applicable), sources of study data, and economic, HCRU, cost, utility, and HRQoL results. Key conclusions and study limitations were also extracted. Due to heterogeneity in study designs and outcomes, no quantitative pooling of study results could be conducted, and study results were synthesized narratively instead.

Quality Assessment

Included records were appraised for quality: economic evaluations using a checklist adapted from Drummond and Jefferson,¹⁹ utility studies using a checklist developed by Papaioannou et al,²⁰ and HRQoL studies using the Downs and Black (1998) checklist.²¹ Quality assessments were conducted by a single reviewer, checked by a second reviewer, and discrepancies resolved by a third, independent, non-author reviewer.

Results

Study Selection

Economic Evaluation Literature Review

Electronic searches identified 426 records reporting economic evaluation data, supplemented by 5 additional records identified through hand searching. After screening, 10 records reporting data from 8 studies were included (Figure 1A).^22–31

Figure 1 continued.

Figure 1 PRISMA flow diagram of included studies in the (A) economic evaluation literature review, (B) HCRU and cost literature review, and (C) utility and HRQoL literature review. Figure adapted from Page et al.18 Abbreviations: cTTP, congenital thrombotic thrombocytopenic purpura; HCRU, healthcare resource utilization; HRQoL, health-related quality of life; iTTP, immune-mediated thrombotic thrombocytopenic purpura; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; TTP, thrombotic thrombocytopenic purpura.

HCRU and Cost Literature Review

Electronic searches identified 986 records reporting HCRU and cost data, supplemented by 3 records identified through hand searching. After screening, 7 records reporting data from 6 studies were included (Figure 1B).^17,32–37

Utility and HRQoL Literature Review

Electronic searches identified 843 records reporting utility and HRQoL data, supplemented by 6 records identified through hand searching. After screening, 22 records reporting data from 14 studies were included (Figure 1C).^{16,22–25,27,28,31,38–49}

Study Characteristics

Key characteristics of included studies across reviews are summarized in Table 2.

Table 2 Key Characteristics of the Included Studies

Economic Evaluation Literature Review

Of the 8 included studies, 3 were published as HTA appraisal documents,^22–24 2 as manuscripts,^27,28 and 3 as conference abstracts.^26,30,31 Three studies were conducted in the US,^28,30,31 2 in Italy,^26,27 2 in the UK^22,23 (England and Scotland), and 1 in Canada.²⁴ All studies evaluated patients with iTTP; none included patients with cTTP.

Six studies reported cost-utility analyses (CUA),^{22–24,26,28,30} whereas 2 reported both CUA and cost-effectiveness analyses.^27,31 Four studies used a combined decision-tree and Markov model approach,^22–24,31 3 used a Markov model alone,^26,27,30 and 1 used separate decision tree and Markov models.²⁸ Further methodological details are provided in Supplementary Table 5.

HCRU and Cost Literature Review

Among the 6 included studies, 5 were published as conference abstracts^{17,32,33,36,37} and 1 as a manuscript.³⁴ Studies were conducted in the US (n=3),^32,34,36 France (n=1),³³ Israel (n=1),³⁷ and internationally (n=1).¹⁷ Only cTTP data were included; any data for iTTP or TTP of unspecified subtype were excluded.

One study reported both HCRU and cost data,³³ 1 reported cost data only,³² and 4 reported HCRU data only.^17,34,36,37 One study used a model-based approach without fully specifying the model design used,³² whereas another used a retrospective, multicenter design.³³ The 4 studies reporting HCRU data only were all retrospective.^17,34,36,37 Of these, 2 were single center,^34,37 and 1 was a multicenter international study.¹⁷ The fourth study was a US healthcare claims database analysis.³⁶

Utility and HRQoL Literature Review

Eight studies reported utility data: 6 as part of CUAs^{22–24,28,38,39} and 2 alongside both CUA and cost-effectiveness data.^27,31 Studies included HTA appraisals (n=3),^22–24 manuscripts (n=4),^27,28,38,39 and a conference abstract (n=1).³¹ Studies were conducted in the US (n=4),^28,31,38,39 the UK (n=2),^22,23 Canada (n=1),²⁴ and Italy (n=1).²⁷ All utility data were derived from studies in iTTP or TTP of unspecified subtype; 6 studies focused on iTTP,^{22–24,27,28,31} and 2 included TTP of unspecified subtype.^38,39 No utility studies focused on cTTP.

Among the utility studies, 2 used indirect data collection methods,^22,23 whereas 6 did not report the data collection method used.^{24,27,28,31,38,39} The most frequently assessed health states were long-term remission following a TTP episode, cognitive impairment, neuropsychological impairment, relapse, and death.

Six studies reported HRQoL data: 3 cross-sectional,^42,46,49 2 observational,^40,43 and 1 RCT.⁴⁸ Studies were conducted internationally (n=2),^40,48 and in France,⁴² Italy,⁴³ the UK,⁴⁶ and the US.⁴⁹ Of these, 1 study included patients with cTTP,⁴⁰ 4 included patients with iTTP,^42,43,46,48 and 1 included patients with TTP of unspecified subtype.⁴⁹

Five studies used the SF-36 instrument for HRQoL assessment, which is a generic measure of health status that assesses HRQoL over 8 domains.^{42,43,46,48,49,51} One study used the Congenital Thrombotic Thrombocytopenic Purpura-Patient Experience Questionnaire (cTTP-PEQ), a disease-specific instrument developed to capture cTTP symptom-related, disease-related, and treatment-related burden.⁴⁰

Study Outcomes

Economic Evaluation Literature Review

All 8 studies evaluated the use of caplacizumab in iTTP from a healthcare system perspective. Reported incremental cost-effectiveness ratios (ICER) varied substantially between studies, reflecting differences in local healthcare costs, model structures, and assumptions.

In the UK, the NICE 2020 appraisal compared caplacizumab in combination with plasma exchange and immunosuppression (with corticosteroids and rituximab) versus plasma exchange and immunosuppression alone in patients aged ≥12 years weighing ≥40 kg. The appraisal used a decision tree model with a 3-month time horizon, followed by a Markov model with a 55-year time horizon, which considered both NHS and social service perspectives. The ICER was reported as 37,986 pounds sterling (GBP) per quality-adjusted life year (QALY) gained in the base case and 39,630 GBP per QALY gained in the adjusted analysis. Caplacizumab was considered cost-effective and recommended for use in combination with plasma exchange and immunosuppression (corticosteroids and rituximab) in England. Key model drivers included the relative risk of acute and long-term mortality, risk of long-term complications, and the price of caplacizumab. The evidence review group noted that uncertainty in survival, and long-term benefit estimates due to limited clinical data were expected given the rarity of iTTP.²²

The SMC 2020 appraisal used a similar modeling approach and reported an ICER of 27,972 GBP per QALY gained and concluded that caplacizumab was cost-effective in Scotland. The SMC recommended its use in combination with plasma exchange and corticosteroid immunosuppression. Key drivers included treatment duration, extrapolated relapse rates, and the relative risk of long-term cognitive impairment.²³

In Canada, the 2020 CADTH appraisal rejected caplacizumab due to limited clinical and long-term data, an unclear target population and missing HRQoL data.²⁵ The 2023 CADTH reappraisal used a decision tree and Markov model, with a 53-year lifetime horizon from a public healthcare perspective. The ICER reported was 215,724 Canadian dollars (CAD) per QALY, and re-analysis by CADTH resulted in an ICER of 269,158 CAD per QALY. Caplacizumab was not considered cost-effective without a 75% price reduction to meet the 50,000 CAD per QALY threshold. Key drivers included extrapolated relapse rates and assumptions about long-term symptom reduction. CADTH also upheld their previous rejection due to continuing uncertainty regarding long-term clinical outcomes and limitations in the models used.²⁴

In Italy, both studies used a Markov model with a 60-year time horizon. They concluded that caplacizumab was cost-effective when used with plasma exchange and corticosteroid immunosuppression, with ICERs of 45,049 Euros (EUR) and 44,572 EUR per QALY gained, which were within the 60,000 EUR per QALY gained threshold defined by the authors.^26,27

In the US, cost-effectiveness results were more variable. Sullivan et al used a decision tree and Markov model with a 55-year lifetime horizon and reported an ICER of 146,300 United States Dollars (USD) per QALY gained, and concluded that caplacizumab was cost-effective against a 150,000–200,000 USD threshold.³¹ In contrast, Goshua et al used a 5-year time horizon and reported ICERs of 3,739,126 USD and 923,053 USD per QALY gained based on the TITAN and HERCULES clinical trials respectively. Their Markov model results reported an ICER of 1,482,260 USD per QALY gained, exceeding their 195,330 USD threshold.²⁸ Butt et al reported an ICER of 7.8 million USD per QALY gained for caplacizumab alone versus plasma-exchange and rituximab, and concluded that a 78% price reduction would be required for cost-effectiveness.³⁰

Overall, caplacizumab was found to be cost-effective in 5 of 8 studies based on local willingness-to-pay thresholds.^{22,23,26,27,31} The remaining 3 studies cited high drug costs and limited long-term data as barriers to cost-effectiveness.^24,28,30

HCRU and Cost Literature Review

Six studies met the inclusion criteria for the HCRU and cost review. Three are discussed in detail below, whereas the remaining 3, which presented limited relevant data, are summarized in Figure 2A.

Figure 2 Summary of outcomes from studies reporting (A) HCRU and cost outcomes (including hospitalization rates, ICU admissions, and monthly cost estimates),17,32–34,36,37 and (B) Utility and HRQoL outcomes (including utility values across health states and HRQoL scores derived from SF-36 and cTTP-PEQ instruments) in patients with TTP.22–24,27,42,46,48 aUtilities for hospitalization and post-discharge calculated using data on utilities for intracranial hemorrhage and ischemic stroke as multipliers. Higher utility scores indicate better health status; bHigher SF-36 scores indicate better health status; cHigher cTTP-PEQ scores indicate greater cTTP-related burden. Abbreviations: CS, corticosteroid; cTTP, congenital thrombotic thrombocytopenic purpura; cTTP-PEQ, Congenital Thrombotic Thrombocytopenic Purpura–Patient Experience Questionnaire; ER, emergency room; EUR, Euro; FFP, fresh-frozen plasma; HCRU, healthcare resource utilization; HRQoL, health-related quality of life; ICU, intensive care unit; IP, inpatient; iTTP, immune-mediated thrombotic thrombocytopenic purpura; MCS, mental component summary; NICE, National Institute for Health and Care Excellence; PCS, physical component summary; PEX, plasma-exchange; PTSD, post-traumatic stress disorder; SDP, solvent/detergent plasma; SF-36, 36-Item Short-Form Survey; SMC, Scottish Medicines Consortium; TTP, thrombotic thrombocytopenic purpura; USD, US dollar.

Goguillot et al performed a retrospective, real-world analysis using data from the French National Hospital Database indexed between January 2015 and December 2020. Among 28 patients with cTTP, 16 (57.0%) had at least one emergency room (ER) visit during the study period.³³ Patients had a median monthly hospitalization rate of 0.5 (range: 0.2–1.5), with a median hospitalization duration of 2.6 days per month (range: 0.7–4.1), and a median monthly cost of 1,536 EUR (range: 720–3,483). This study also noted that 32.1% of the cohort were pregnant women, and that non-pregnant adults experienced longer hospital stays and incurred higher costs (Figure 2A).

Coppo et al performed a retrospective, multinational chart review of 78 patients with cTTP. At study index, 4 acute events were reported, all requiring hospitalization, and 1 patient was admitted to an intensive care unit (ICU).¹⁷ Over the 2-year study period (January 2009–December 2010) 55 (70.5%) patients experienced 92 acute events, of which 85 (92.4%) required hospitalization and 32 (37.6%) resulted in an ICU admission (Figure 2A).

Oladapo et al conducted a US-based economic modeling study which used input parameters from published studies and expert opinion rather than real-world data. They estimated the lifetime societal cost of cTTP to exceed 5 million USD per patient for treatment with fresh-frozen plasma (FFP) and solvent/detergent plasma (SDP). Estimated direct costs per patient were 1.2 million USD and 1.7 million USD, respectively.³² Lifelong treatment, prophylaxis, recurrent hospitalizations, complications, and productivity losses were identified as key contributors to total costs (Figure 2A).

Overall, the included studies reported frequent hospitalizations and ER visits, as well as considerable direct and indirect costs associated with cTTP.

Utility and HRQoL Literature Review

Utility Data

Overall, 8 studies reported utility data, summarized below and in Figure 2B.

The NICE 2020 appraisal reported a baseline utility of 0.87 before an iTTP episode.²² As no HRQoL data were collected in the HERCULES trial, the company estimated utilities using model-based assumptions. The SMC 2020 appraisal also reported an estimated baseline utility of 0.87.²³ Utility values during hospitalization ranged from 0.37 (NICE 2020 appraisal, based on proxy utilities for patients with a history of stroke)²² to 0.644 (CADTH 2023 appraisal).²⁴ The SMC 2020 appraisal reported better utility scores during acute iTTP events for patients treated with caplacizumab (range: 0.67–0.72) compared with those receiving plasma exchange and corticosteroids (range: 0.63–0.70)²³ (Figure 2B).

Disutility values varied across studies: Di Minno et al estimated a disutility of 0.230 during acute iTTP events, whereas Schleinitz et al reported a median disutility value of 0.027 for clopidogrel-associated TTP events.^27,38,39 Utility values at hospital discharge ranged from 0.66 (NICE 2020 appraisal) to 0.736 (CADTH 2023 appraisal). This indicates that scores did not return to pre-episode levels following acute treatment and suggests potential long-term impacts on HRQoL.^22,24 During remission, utility scores for patients with cognitive impairment varied (range: 0.61–0.93), with lower scores associated with greater impairment (Figure 2B). Goshua et al assigned a utility value of 0.1 to patients experiencing a relapse. This value is low relative to other studies and reflects a study-specific assumption that relapse may result in a marked decline in patient utilities²⁸ (Figure 2B).

HRQoL Data

Six studies reported HRQoL outcomes: 5 used the generic SF-36 instrument, and 1 used the disease-specific cTTP-PEQ. These data are summarized in Figure 2B.

Scully et al reported long-term follow-up data from the HERCULES trial in 104 patients with iTTP (efficacy population: caplacizumab, n=49; placebo, n=29). Over 36 months, patients treated with caplacizumab showed greater improvement in SF-36 physical component summary (PCS) scores (+3.1 vs +1.2) but a worsening in mental component summary (MCS) scores (−1.9 vs −0.7) compared with placebo.⁴⁸ Holmes et al performed a cross-sectional study of 50 UK-based patients with iTTP and found that patients with prior iTTP events had mean (SD) SF-36 PCS and MCS scores of 42.16 and 33.61, respectively, which were both worse than population norms (Figure 2B).⁴⁶

Selvakumar et al reported that 26 US-based patients with prior iTTP events had worse mean SF-36 scores across all domains compared with matched controls.⁴⁹ Similarly, Riva et al performed a cross-sectional study of 35 patients in Italy at least 3 months after they experienced an iTTP episode and found that both PCS and MCS scores were worse than that of a matched general population, with the largest difference observed in the MCS score.⁴³

Azoulay et al conducted a cross-sectional study of 52 patients in France a mean of 72 months post-discharge from hospital and reported median (IQR) SF-36 score data. Among those with post-traumatic stress disorder (PTSD), 29% of the study cohort, median (IQR) PCS and MCS scores were significantly worse than among patients without PTSD (PCS: 58 vs 64; MCS: 52 vs 78; p=0.05).⁴²

Oladapo et al used the cTTP-PEQ in a prospective study of 36 patients with cTTP who received either prophylactic or on-demand treatment. The mean cTTP-PEQ score improved from 33.94 at baseline to 30.95 at day 14, representing an improvement of −3.15 from baseline, indicating a reduction in HRQoL burden (Figure 2B).⁴⁰

Quality Assessment

In the economic evaluation literature review, the majority of studies scored “Yes” across most items on the Drummond and Jefferson checklist, indicating that they adhered to accepted methodological standards and had a generally low risk of bias.¹⁹ Similarly, in the utility and HRQoL literature review, most studies reporting HRQoL data were rated as high quality based on the Downs and Black checklist.²¹ The quality of studies reporting utility data was more variable, as assessed using the Papaioannou checklist, with common limitations including unclear reporting of patient attrition and handling of missing data.²⁰ Overall, the methodological quality of included studies was considered acceptable to high.

Discussion

This SLR provides a comprehensive summary of the available literature on economic evaluations of iTTP treatments, the HCRU and costs associated with cTTP, and utility and HRQoL impacts across the TTP spectrum. Notably, no economic evaluations were identified for cTTP, confirming a critical evidence gap. These findings demonstrate that iTTP is associated with meaningful healthcare costs driven by treatment requirements, disease morbidity, and mortality. Despite this, results from cost-effectiveness studies varied. Caplacizumab was considered cost-effective for treating acute iTTP events in England, Scotland, Italy, and one US-based study. However, in other US studies and in Canada, it was not deemed cost-effective due to high drug costs relative to local willingness-to-pay thresholds, and in Canada the data were considered insufficient to account for potential reductions in long-term TTP impacts. Overall, caplacizumab was found to be cost-effective in 5 out of 8 evaluations. The remaining 3 studies cited high drug costs and limited long-term data as barriers to cost-effectiveness. These findings underscore the importance of local context, pricing strategies, and long-term outcome data in determining the value of caplacizumab.^{22–24,26–28,30,31}

This review also provides initial insights into cTTP, particularly regarding HCRU and cost burden. Although the evidence base is limited and largely derived from small patient cohorts, available data suggest that cTTP imposes a meaningful, but not yet fully quantified burden on patients and healthcare systems. For example, Goguillot et al reported a median (range) hospitalization rate of 0.5 (0.2–1.5) per month, with a median (range) duration of 2.6 (0.7–4.1) days per month.³³ These data suggest that patients with cTTP experience frequent and prolonged hospital interactions, which may substantially disrupt their lives and work productivity due to missed work time. This is also consistent with Oladapo et al, which estimated an indirect lifetime cost of cTTP of 4.2 million USD per patient, with approximately 1.6 million USD of this cost (38%) due to missed work related to treatment.³² Together these findings provide early evidence of a potentially high disease burden, reinforcing the chronic and disruptive nature of cTTP, while also highlighting the need for further cTTP-specific studies to validate these estimates.

Utility data captured from studies in iTTP or TTP of unspecified subtype indicate that patients with TTP experience significant reductions in quality of life. Baseline utility scores before TTP events were already worse than those in population controls, with further reductions during hospitalization. Scores partially improved post-discharge, but did not return to population norms.^22–24 Similarly, HRQoL data captured using the SF-36 instrument revealed that patients had worse scores across domains compared with the general population. SF-36 MCS scores declined over time, suggesting worsening mental health following hospital discharge.^43,46,49 This may reflect neurological and cognitive impacts from TTP-related ischemia, manifesting as headaches, fatigue, depression, and reduced concentration.^52–54 Notably, some patients reported symptoms of PTSD following TTP events, highlighting the profound psychological burden of TTP.⁴² As these psychological and cognitive sequelae of TTP are not well captured by generic HRQoL tools, these data highlight the potential value of disease-specific instruments such as the cTTP-PEQ, which provides cTTP-specific assessment of HRQoL.⁴⁰

Limitations

Although cTTP and iTTP both occur due to ADAMTS13 deficiency, they may differ in disease trajectory. Additionally, they may require different treatment approaches, with cTTP often requiring lifelong prophylaxis, whereas iTTP typically occurs in discrete episodes. These differences mean the economic evaluation and HRQoL data from iTTP and unspecified TTP patient populations included in this study may not represent the overall burden experienced by patients with cTTP. Future cTTP-specific economic evaluation, utility, and HRQoL studies are needed to address the data gaps identified by this review. Several included abstracts lacked methodological detail, limiting comparability across studies. There was variability in study quality, with some studies reporting on very small patient populations. For example, Ibrahim et al reported data from only 2 patients, limiting generalizability.³⁴ No disease-specific utility values were available for iTTP or cTTP. Studies such as the NICE 2020 appraisal and Di Minno et al relied on proxy data from unrelated conditions (ie, stroke, sepsis, severe injury, and sickle cell anemia).^22,27 Although pragmatic, these proxies may not fully capture the distinct impact of TTP, potentially leading to overestimation or underestimation of patient burden and treatment effects in cost-effectiveness analyses. This limitation is critical, as economic models and HTA decisions depend on accurate, disease-specific utility values. Heterogeneity in study designs, outcome measures and reporting methods further limited comparisons between studies and prevented any meta-analyses. Consequently, findings should be interpreted with caution, particularly when extrapolating to patients with cTTP, or to broader patient populations.

Conclusions

This review highlights a critical gap in the literature: the absence of economic evaluations in cTTP. These data show that economic findings in TTP are primarily derived from iTTP populations, where iTTP is associated with meaningful economic burden driven by frequent HCRU and productivity losses. As direct evidence on economic impacts in cTTP are limited, findings should be interpreted as preliminary for this patient population. Data also indicate that patients with cTTP, iTTP, and unspecified TTP experience substantial reductions in HRQoL and utility scores beyond hospital discharge, although most HRQoL and utility evidence originates from iTTP or unspecified TTP populations. These findings underscore the need for novel, effective TTP treatments that may reduce long-term burden. Future research should prioritize robust, disease-specific utility data and economic evaluations of emerging cTTP therapies to support value-based decisions by HTA agencies and payers.