Cost-Effectiveness of Rapid Hemosil Versus in-House and Send-out ADAMTS13 Activity Testing in the Care of Patients with Immune Thrombotic Thrombocytopenic Purpura

INTRODUCTION

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy requiring immediate treatment when the pretest probability is intermediate or high, a probability determined with the use of the PLASMIC and/or French clinical scores. Ruling out iTTP with a biomarker ADAMTS13 activity level can take several days at most hospital systems in the United States, all the while empiric treatment for iTTP accrues risks and costs. The newly developed rapid turnaround and fully automated, chemiluminescent immunoassay (HemosIL) reveals high concordance with chromogenic ELISA and FRET-based assays, the diagnostic standard-of-care. Unlike rapid in-house testing requiring technical expertise, the HemosIL assay can abrogate the cost and risk exposure associated with treating patients for iTTP whose biomarker activity level later rules out this diagnosis. Despite existing concerns of testing cost, we hypothesized that rapid and fully automated diagnostic testing would be cost-saving with similar quality-adjusted life-expectancy, as compared to both in-house FRET-based evaluation and send-out FRET-based evaluation. We further posited that this effect would be greater in the context of 1) intermediate- versus high-probability PLASMIC scores, and 2) patients treated with caplacizumab versus without. We sought to fill these gaps by conducting the first cost-effectiveness evaluation of the HemosIL assay in patients treated with and without caplacizumab.

METHODS

For this independent analysis free of industry influence, we built a Markov simulation of patients with intermediate- (PLASMIC score =5) or high- (PLASMIC score 6-7) pretest probability for iTTP empirically treated while awaiting results under three testing strategies: 1) HemosIL rapid turnaround (<1 hour), 2) 24-hour in-house, FRET-based evaluation, and 3) 72-hour send-out, FRET-based evaluation. For transition probabilities, our model was informed by extensive literature published on test characteristics, as well as derivation and validation cohorts for the PLASMIC score. Adverse events for therapeutic plasma exchange (TPE) and caplacizumab were informed from clinical trial data and real-world data, with costs in 2023 US dollars sourced from the Centers for Medicare and Medicaid Services. Utilities were informed by literature on critically ill adults hospitalized in the medical intensive care unit and were originally derived with validated EuroQol methodology. Age- and sex-adjusted background mortality were employed. The primary outcome was the incremental cost-effectiveness ratio (ICER) or, the incremental net monetary benefit (iNMB) if the intervention (HemosIL) was found to be cost-saving, reported over a 3-day time-horizon and across accepted willingness-to-pay thresholds in USD per quality-adjusted life-year (QALY). Four scenario analyses were examined: 1) PLASMIC 5 with caplacizumab, 2) PLASMIC 5 without caplacizumab, 3) PLASMIC 6-7 with caplacizumab, 4) 6-7 PLASMIC without caplacizumab. We concluded by executing deterministic and probabilistic sensitivity analyses, varying all parameter estimates +/-50% and capturing uncertainty in all parameters simultaneously over 10,000 Monte Carlo simulations.

RESULTS

Across all scenario analyses, testing with HemosIL was cost saving and accrued the same amount of QALYs (Table 1). These savings with HemosIL ranged from $2,900 (PLASMIC 6-7, without caplacizumab) through $44,700 (PLASMIC 5, with caplacizumab) per-patient-tested versus send-out, and from $800 to $19,800 versus in-house testing. No parameter variation changed the outcome of any scenario to favoring a non-HemosIL testing strategy in deterministic sensitivity analysis. In probabilistic sensitivity analyses across accepted willingness-to-pay thresholds in the United States, HemosIL was favored in 100% of iterations in the PLASMIC 5 context (with and without caplacizumab), and 99.9% and 98.6% in the PLASMIC 6-7 context with and without caplacizumab use, respectively (Table 2).

CONCLUSION

Despite cost concerns, HemosIL testing for patients with intermediate- or high-risk PLASMIC score produces significant cost savings for each patient tested and empirically treated. This is achieved by reducing the costs associated with unnecessary therapeutic plasma exchange and caplacizumab therapy.