Cost Effectiveness of Rituximab As Adjunctive Therapy in Reducing Apheresis Procedures and Hospital Length of Stay in Relapsed Thrombotic Thrombocytopenic Purpura
Authors: Goshua George , Gokhale Amit , Hendrickson Jeanne E. , Tormey Christopher , Lee Alfred Ian 
Published: October 2019

Abstract
Introduction: Rituximab at standard dosing (375 mg/m2 weekly for 4 weeks) is effective in preventing thrombotic thrombocytopenic purpura (TTP) relapse and is recommended as a therapy of choice along with plasmapheresis (PLEX) in the UK expert-based guidelines on TTP (category IB), although it is not yet universally viewed as standard of care. There is also emerging data for low dose rituximab (100 mg weekly for 4 weeks) in the treatment of relapsing TTP with mixed data on efficacy as compared to standard dose rituximab. With this in mind, we conducted a retrospective chart review to examine the financial cost of treating a patient hospitalized for a TTP relapse with rituximab, PLEX and steroids compared to PLEX and steroids only. The purpose of this study was to determine an average savings per patient of utilizing rituximab as an adjunctive agent in the inpatient setting.
Methods: Chart records for patients admitted to a major academic center with a diagnosis of TTP, defined as laboratory and smear evidence of microangiopathy with ADAMTS13 level of 10% or less or evidence of microangiopathy in a patient with a prior established diagnosis of TTP, were reviewed. The clinical course of all patients including treatments received and length of stay (LOS) for each hospitalization was recorded. TTP relapse was defined as hospitalization for TTP more than 30 days after hospital discharge. An average hospital cost per patient with a relapsed episode of TTP was calculated utilizing average costs for LOS and for PLEX during their hospitalization for TTP relapse. The average wholesale price of a fixed dose of rituximab for one cycle (defined as four doses of 375 mg/m2) was utilized to calculate the total cost of rituximab treatment. A cost superiority determination per patient was calculated by comparing the total cost of relapsed TTP hospitalizations versus the cost of rituximab administered in the inpatient setting. All costs are listed in United States Dollar (USD).
Results: A total of 28 patients spanning 25 years were hospitalized for a TTP exacerbation. The median age of these patients was 40.7 with ADAMTS13 level of 6.5% at diagnosis and 3.2% at relapse. Of 28 patients, 15 patients had relapsed TTP for a total of 50 hospitalizations. All 15 relapsed patients were treated with PLEX and steroids during every hospitalization. The average number of inpatient PLEX procedures performed on patients admitted for relapsed TTP was 7.1 with an average hospital LOS of 9.6 days. 13 of the 15 relapsed patients received a total of 15 cycles of rituximab while 2 patients did not receive any rituximab. Of the 13 rituximab-treated patients, 10 received one cycle of rituximab, with 9 achieving a sustained remission and the other patient experiencing a relapse of TTP that was not treated with any additional rituximab; 2 received a second cycle, with both achieving a sustained remission, although 1 had an allergic reaction during the second cycle that led to discontinuation of rituximab. In total, 11 of 15 episodes of relapsed TTP were treated with rituximab with 73% achieving a sustained remission over a median follow up time of 36 months.
In our study cohort, use of rituximab would have led to a reduction in 182 total hospitalization days and 135 total PLEX procedures, yielding a cost savings of $59,918.40 per relapse of TTP. This would be offset by a cost of $30,894 for each cycle of standard dose rituximab, for a net cost savings of $29,024.40 per occurrence of TTP relapse treated with rituximab. A similar cost analysis utilizing low dose rituximab yielded a net cost savings of $55,582.40 per relapse of TTP, assuming similar efficacy of low and standard dose rituximab.
Conclusions: The addition of rituximab to PLEX and steroids in treatment of relapsed TTP is more cost effective than PLEX and steroids alone, owing to the high efficacy of rituximab and the cumulative costs of PLEX and hospital LOS. This cost superiority of rituximab holds both for standard and low dose rituximab, assuming similar efficacy of the latter. Although not calculated in our analysis, administration of rituximab in the outpatient rather than inpatient setting would result in further cost savings. Therefore, from a cost efficiency standpoint, rituximab should be incorporated into treatment paradigms for relapsed TTP.

Disclosures
No relevant conflicts of interest to declare.