Cost-effectiveness of adding rituximab to splenectomy and romiplostim for treating steroid-resistant idiopathic thrombocytopenic purpura in adults

BMC Health Services Research

Toru Takebayashi¹  Yuji Sato³  Shunya Ikeda²  Yoshitaka Miyakawa⁴  Kayoko Kikuchi³ 

[1] Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan;Department of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara City, Tochigi, Japan;Center for Clinical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan;Department of General Internal Medicine, Saitama Medical University Hospital, 38 Morohongo Moroyamamachi, Irimagun, Saitama, Japan

关键词: Cost-effectiveness;    Rituximab;    Romiplostim;    Splenectomy;    ITP;   

Others  :  1089870
DOI  :  10.1186/s12913-015-0681-y

 received in 2014-02-21, accepted in 2015-01-06,  发布年份 2015

【 摘 要 】

Background

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which the platelet count falls to <100 × 10⁹/L. Corticosteroids are recommended as the first-line treatment, splenectomy is recommended as the second-line treatment, and thrombopoietin receptor agonists (TPO-RAs) and rituximab are recommended as the third-line treatments for ITP in Japanese ITP treatment guidelines. However, in Japan, rituximab is not eligible for reimbursement for the treatment of ITP. The cost-effectiveness of ITP treatment has not been investigated in Japan. Therefore, in this study, the cost-effectiveness of adding rituximab treatment to the existing treatments indicated for ITP in Japan, namely splenectomy and the TPO-RA romiplostim, was investigated based on the scenario that rituximab is eligible for reimbursement in Japan as a treatment for ITP.

Methods

The efficacy endpoint was set as the number of years with a platelet count ≥30 × 10⁹/L. The analysis was conducted from the healthcare payer’s perspective. If the first treatment is ineffective or relapse occurs, then the patient is given the following treatment. The analyzed treatment order consisted of three patterns: splenectomy-romiplostim (sequence 1), splenectomy-romiplostim-rituximab (sequence 2), and splenectomy-rituximab-romiplostim (sequence 3). A Markov model was built for ITP, and the analysis period was set as 2 years. The discount rate was an annual rate of 2%.

Sensitivity analyses of the efficacy of splenectomy, romiplostim, and rituximab; treatment cost; and romiplostim dose were performed.

Results

The expected costs per patient over a 2-year period for sequences 1, 2, and 3 were USD 40,980, USD 39,822, and USD 33,551, respectively. The expected years with a platelet count ≥30 × 10⁹/L for the three sequences were 1.75, 1.79, and 1.78 years, respectively. The sensitivity analyses illustrated that the results of the base case analysis were robust.

Conclusions

Adding rituximab to standard treatment for ITP (sequences 2–3) is less costly and marginally more effective than standard therapy in adults. According to the study results, if rituximab is reimbursed for the treatment of ITP in Japan, medical expenses are expected to decline.

【 授权许可】

   
2015 Kikuchi et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A: Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001, 97:2549-54.
• [2]Fujimura K, Miyakawa Y, Kurata Y, Kuwana M, Tomiyama Y, Murata M: Reference guide for management of adult idiopathic thrombocytopenic purpura (ITP) 2012 version. Rinsho Ketsueki 2012, 53:433-42. (in Japanese)
• [3]Kojouri K, Vesely SK, Terrell DR, George JN: Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004, 104:2623-34.
• [4]Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL: Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008, 371:395-403.
• [5]Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA: The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011, 117:4190-207.
• [6]Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ: International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010, 115:168-86.
• [7]Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, Fraser GA, Lim W, Kelton JG: Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007, 146:25-33.
• [8]Lee LH, Caguioa P, Chin NS, Chiou TJ, Lee JW, Miyakawa Y, Tambunan KL, Chong BH: Chronic adult primary immune thrombocytopenia (ITP) in the Asia-Pacific region. Int J Hematol 2011, 94:142-9.
• [9]Mowatt G, Boachie C, Crowther M, Fraser C, Hernández R, Jia X, Ternent L: Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal. Health Technol Assess 2009, 13(Suppl 2):63-8.
• [10]Boyers D, Jia X, Jenkinson D, Mowatt G: Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal. Pharmacoeconomics 2012, 30:483-95.
• [11]Lee D, Thornton P, Hirst A, Kutikova L, Deuson R, Brereton N: Cost effectiveness of romiplostim for the treatment of chronic immune thrombocytopenia in Ireland. Appl Health Econ Health Policy 2013, 11:457-69.
• [12]Shirasugi Y, Ando K, Miyazaki K, Tomiyama Y, Iwato K, Okamoto S, Kurokawa M, Kirito K, Hashino S, Ninomiya H, Mori S, Yonemura Y, Usuki K, Wei H, Lizambri R: An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura (ITP). Int J Hematol 2012, 95:652-9.
• [13]Thomsen RW, Schoonen WM, Farkas DK, Riis A, Jacobsen J, Fryzek JP, et al.: Risk for hospital contact with infection in patients with splenectomy: a population-based cohort study. Ann Intern Med. 2009, 151:546-55.
• [14]Assessment report of romiplostim [http://www.info.pmda.go.jp/shinyaku/P201100020/230124000_22300AMX00437_A100_2.pdf] (in Japanese)
• [15]Wang M, Zhang M, Zhou J, Wu Z, Zeng K, Peng B, Niu T: Predictive factors associated with long-term effects of laparoscopic splenectomy for chronic immune thrombocytopenia. Int J Hematol 2013, 97:610-6.
• [16]Zaja F, Volpetti S, Chiozzotto M, Puglisi S, Isola M, Buttignol S, Fanin R: Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia. Am J Hematol 2012, 87:886-9.
• [17]Pasa S, Altintas A, Cil T, Danis R, Ayyildiz O: The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura. J Thromb Thrombolysis 2009, 27:329-33.
• [18]Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, Vekhoff A, Chauveheid MP, Stirnemann J, Galicier L, Bourgeois E, Haiat S, Varet B, Leporrier M, Papo T, Khellaf M, Michel M, Bierling P: Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood 2008, 112:999-1004.
• [19]Ashizawa K, Eguchi K: Appearance frequency and time of steroid side effect. Rinsho Kenkyu 2001, 78:1424-6. (in Japanese)
• [20]Stasi R, Murali M, Michel M, Viallard JF, Giagounidis A, Janssens A, Legg J, Deuson R, Danese MD: Evaluation of bleeding-related episodes in patients with immune thrombocytopenia (ITP) receiving romiplostim or medical standard of care. Int J Hematol 2012, 96:26-33.
• [21]Ministry of Health, Labor and Welfare. abridged life table 2011 version [http://www.mhlw.go.jp/toukei/saikin/hw/life/life10/] (in Japanese)
• [22]Guidelines for economic evaluation of healthcare technologies in Japan. Tokyo: Research group on economic evaluation for Japanese public medical benefit; 2013. http://www.mhlw.go.jp/file/05-Shingikai-12404000-Hokenkyoku-Iryouka/0000033418.pdf (in Japanese)
• [23]Xie F, Blackhouse G, Assasi N, Campbell K, Levin M, Bowen J, et al.: Results of a model analysis to estimate cost utility and value of information for intravenous immunoglobulin in Canadian adults with chronic immune thrombocytopenic purpura. Clin Ther. 2009, 31:1082-91.