In February 2019, the FDA approved the anti–von Willebrand factor immunoglobulin fragment caplacizumab as the only agent specifically indicated for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP). But, with a list price of $270,000, the cost of the treatment outweighs its benefits, according to results of a cost-effectiveness analysis published in Blood.
Researchers led by George Goshua, MD, reported that caplacizumab had an incremental cost-effectiveness ratio (ICER) of nearly $1.5 million for caplacizumab over a 5-year period, compared with standard of care (SOC; therapeutic plasma exchange [TPE] and corticosteroids). “It was shocking to see [in this study] just how exorbitant the cost of caplacizumab is and how the cost of caplacizumab alone was the single largest factor contributing to the ICER,” Dr. Goshua, a second-year hematology fellow at Yale School of Medicine and Chair-Elect of the Hemostasis and Thrombosis Research Society Fellows Network, told ASH Clinical News.
TPE and corticosteroids are substantially less costly compared with caplacizumab, as is up-front immunomodulation with rituximab, which leads to long-lasting remissions in 60 to 80% of patients, Dr. Goshua added. “Caplacizumab accelerates platelet count recovery time during an acute aTTP flare and hence improves hospital length of stay, including intensive care unit stay and decreased number of TPE sessions,” he said. “Unlike immunomodulatory drugs like rituximab, caplacizumab does not have known long-term disease-modifying properties.”
In this study, Dr. Goshua and investigators built decision-tree models and a Markov model to estimate the cost-effectiveness of adding caplacizumab to SOC, using 12-month follow-up data from the phase II TITAN trial and 1-month follow-up data from the pivotal phase III HERCULES trial. “Our hypothesis was that the significant list price of the medication would yield an ICER that would not be justified by the willingness-to-pay metrics, even in the U.S.,” he said.
Treatment costs were calculated using U.S. list prices and facility costs. Researchers estimated treatment of a TTP episode would require four individual rituximab 375 mg/m2 doses, at a cost of $7,724 per dose; treatment with caplacizumab was $270,000 per episode. Other associated costs accounted for in the model included the institution’s costs for number of TPE sessions ($6,000/TPE session), intensive care unit length of stay ($1,043/day), and total hospital length of stay ($490/day).
Over 5 years, the projected ICER in the Markov model was $1,482,260, which the researchers noted significantly exceeded the accepted 2019 U.S. willingness-to-pay threshold of $195,300. In a probabilistic sensitivity analysis, SOC alone was favored over SOC plus caplacizumab in all 10,000 iterations.
“It was shocking to see [that] the cost of caplacizumab alone was the single largest factor contributing to the ICER.”
—George Goshua, MD
In a cost-effectiveness acceptability curve, caplacizumab plus SOC became the preferred treatment strategy over SOC alone in just 0.03% of 10,000 iterations when the minimum willingness-to-pay threshold was set at $1,037,405. If the minimum willingness-to-pay amount was increased to $2,142,668, caplacizumab was preferred in all iterations.
The direct cost of caplacizumab had the largest effect on ICER in one-way sensitivity analyses, the authors noted, and reducing the cost of caplacizumab demonstrated the greatest impact on lowering the ICER. They also explained that their models used the extremes of the number of TPE sessions and inpatient lengths of stays reported in the TITAN and HERCULES trials to maximize and minimize, respectively, such costs in the SOC and caplacizumab groups. “Considering all of these factors, the ICER for adding caplacizumab to SOC in treating acquired TTP is likely to be higher than the values calculated in our models,” they wrote.
Limitations of this study included the variable distribution of rituximab in the TITAN trial, the lack of data on bleeding costs in the investigator-built models, as well as the relatively short follow-up data available for both the TITAN and HERCULES trials.
“We hope this study spurs further work in decision analyses in nonmalignant hematology where financial toxicity can be just as negatively impactful as it is in oncology,” concluded Dr. Goshua.
Study authors report no relevant conflicts of interest.
Goshua G, Sinha P, Hendrickson JE, et al. Cost-effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood. 2020 December 6. [Epub ahead of print]
Caplacizumab is used in aTTP because of its ability to rapidly increase platelet counts and stop ischemic symptoms. But, like TPE, caplacizumab is only a temporizing treatment. It has no effect on the autoimmune pathogenesis.
Daily caplacizumab treatments continue until immunosuppression causes ADAMTS13 recovery. While treatment continues, patients remain asymptomatic. “Refractory TTP” will become obsolete with this approach, but caplacizumab is mind-bogglingly expensive. Is it worth it? Dr. Goshua and colleagues conclude it is not, and I agree – but that’s for today.
For tomorrow, my dream is that caplacizumab will replace TPE. TPE requires specialized personnel and equipment, and there may be critical complications. Caplacizumab is delivered as a 1 mL subcutaneous injection, allowing for home use.
With caplacizumab, hospitalization may be brief and clinically important bleeding is rare. Last year in our practice, we had a patient for whom hospitalization was not needed.1 She was well-known to us from previous TTP relapses. At a routine clinic visit, she had mild thrombocytopenia and her blood smear showed schistocytes. Relapse seemed certain, but she asked, “Do I have to go into the hospital again? Do I have to get that plasma treatment?” What followed was a perfect example of shared decision-making: She received her initial caplacizumab dose and went home. The next day, TTP was confirmed by ADAMTS13 deficiency; her platelet count had increased and her symptoms had improved. Subsequently, rituximab was begun. She recovered.
Eight other patients have been successfully treated with caplacizumab without TPE (for religious refusal of plasma, anaphylactic reaction, no venous access for TPE, patient preference). If this becomes future management of TTP, Dr. Goshua and colleagues will need to repeat their analysis. Caplacizumab may then be cost-effective.
James N. George, MD
University of Oklahoma Health Sciences Center
Oklahoma City, OK
- Sukumar S, Cataland SR, George JN. Shared decision making, thrombotic thrombocytopenic purpura, and caplacizumab. Am J Hematol. 2020;95:E76-E77.