ANALISIS FARMAKOEKONOMI ASAM ZOLEDRONAT DAN ASAM IBANDRONAT SEBAGAI TERAPI METASTASE TULANG PADA MULTIPLE MIELOMA

NUTRISIA AS, Tri Murti Andayani; Dwi Endarti; Kartika Widayati

2021 | Disertasi | DOKTOR ILMU FARMASI

Asam zoledronat dan asam ibandronat merupakan terapi metastase tulang pada multiple mieloma (MM). Asam zoledronat lebih efektif mencegah skeletal related event (SRE) namun adverse event (AE) pada fungsi ginjal dan osteonecrosis rahang (ONJ) lebih banyak terjadi. Tujuan penelitian ini adalah menganalisis besarnya biaya terapi metastase tulang pada MM dengan asam zoledronat dan asam ibandronat, menganalisis besarnya nilai incremental cost effectiveness ratio (ICER) per efektivitas dalam mencegah SRE dan menganalisis apakah asam zoledronat lebih cost efektif terhadap asam ibandronat berdasarkan nilai ICER per quality adjusted life years (QALY) pada pasien MM. Penelitian farmakoekonomi ini dilakukan melalui analisa cost of illness (COI), cost effectiveness analysis (CEA) dan cost utility analysis (CUA). Rancangan penelitian cross sectional digunakan pada penelitian COI. Biaya dihitung dari perspektif provider (biaya medis langsung) dan societal (biaya non medis langsung dan biaya tidak langsung). Cohort retrospektif digunakan pada penelitian CEA dengan outcome klinik berupa time to SRE dan persentase AE. ICER per efektivitas dihitung sebagai biaya per 1 tahun time to SRE. CUA menggunakan pendekatan modelling, utility sebagai parameter model diteliti dengan rancangan cross sectional. Markov model dengan 3 state yaitu No SRE, SRE dan death, siklus 4 minggu dan time horizon life time. Model disimulasikan pada perspektif provider dan societal. ICER dianalisa sebagai cost per QALY kemudian dibandingkan dengan cost effectiveness treshold (Rp. 177.300.000). Analisa sensitivitas satu arah, sensitivitas probabilistik dan CEA curve (CEAC) dilakukan untuk menguji ketahanan model. Biaya medis obat asam zoledronat setiap siklus lebih murah dari asam ibandronat (Rp. 1.765.430 versus Rp. 2.513.438). Biaya non medis langsung dan biaya tidak langsung pada kondisi SRE lebih besar dari pada kondisi No SRE. Time to SRE asam zoledronat adalah 2,12 bulan lebih lama dari asam ibandronat. Hasil observasi AE pada asam zoledronat dan asam ibandronat pada ganguan ginjal adalah 2,5% (1/40) versus 3,3% (1/30) dan gejala mirip flu adalah 2,5% (1/40) versus 6,7% (2/30). Asam zoledronat memberikan tambahan QALY sebesar 0,95 tahun dibandingkan asam ibandronat. Nilai ICER per QALY asam zoledronat terhadap asam ibandronat pada asumsi tanpa kemoterapi dengan perspektif provider adalah negatif Rp. 17.394.174, perspektif societal adalah negatif Rp. 66.779.334. Penambahan biaya kemoterapi menghasilkan nilai ICER per QALY sebesar negatif Rp. 17.296.207 sampai dengan negatif Rp.17.286.507 pada perspektif provider serta negatif Rp. 69.074.942 sampai dengan negatif Rp. 68.980.953 perspektif societal. Biaya pada terapi asam zoledronat Rp. 87.694.119(SD:Rp. 57.224.493) sedangkan pada terapi asam ibandronat adalah Rp. 106.856.703(SD:Rp. 85.302.322). Nilai ICER adalah negatif Rp. 108.467.458 per 1 tahun time to SRE. Asam zoledronat cost efektif (cost saving) terhadap asam ibandronat dalam mencegah SRE. Implikasi hasil penelitian adalah asam zoledronat merupakan rekomendasi untuk terapi metatase tulang terbaik bagi MM sehingga perlu dilakukan analisa farmakoekonomi lebih lanjut bagi obat-obatan pencegah SRE lain untuk dimasukkan ke dalam formularium nasional. Kata kunci : asam zoledronat, asam ibandronat, metastase tulang, multiple mieloma, farmakoekonomi

Zoledronic acid and ibandronic acid are therapy of bone metastases in multiple myeloma (MM). Zoledronic acid is more effective for the prevention of skeletal-related events (SRE) but the adverse events (AE) of kidney function and osteonecrosis of the jaw (ONJ) is more common. The study aimed to analyze the value of cost therapy of bone metastasis with zoledronic acid and ibandronic acid in MM, to analize the value of incremental cost effectiveness ratio (ICER) per effectivity of SRE prevention and to analyze wether zoledronic acid was more cost efective compared to ibandronic acid from ICER per quality adjusted life years (QALY) in MM patients. The pharmacoeconomic study was done through analysis of cost of illness (COI), cost effectiveness analysis (CEA) dan cost utility analysis (CUA). The cross sectional research design was used in COI research. costs were calculated from the provider's perspective (direct medical cost) and societal (direct non-medical costs and indirect costs). The cohort retrospective design was used in CEA research, the clinical outcomes were time to SRE and AE percentage. The ICER per effectiveness of SRE prevention was calculated as cost per one year time to SRE. Modelling approach was used in CUA research, utility as model parameter was studied with a cross-sectional design. Markov model with three states, namely No SRE, SRE, and death with a four-week cycle and time horizon life time. The model was simulated from a provider and societal perspective. ICER was analyzed as cost per quality-adjusted life years (QALY) gained. ICER per QALY gained compared to the cost-effectiveness threshold (Rp. 177,300,000). One-way sensitivity analysis, probabilistic sensitivity analysis, and CEA curve (CEAC) were performed to test the model's robustness. The medical cost of zoledronic acid per cycle was less than ibandronic acid (IDR 1,765,430 versus IDR 2,513,438). The direct non-medical costs and indirect costs in the SRE condition are greater than the No SRE conditions. The time to SRE of zoledronic acid was 2.12 months longer than ibandronic acid. The results of AE's observations on zoledronic acid and ibandronic acid in kidney disorders were 2.5% (1/40) versus 3.3% (1/30) and flu like symptoms were 2.5% (1/40) versus 6.7% (2/30). Zoledronic acid provided an additional QALY of 0.95 years compared to ibandronic acid. The ICER value per QALY of zoledronic acid against ibandronic acid on the assumption without chemotherapy from the provider perspective was negative IDR 17,394,174, the societal perspective was negative IDR 66,779,334. The addition of chemotherapy costs resulted ICER value per QALY of negative IDR 17,296,207 to negative IDR 17,286,507 from the provider's perspective and negative IDR 69,074,942 to negative IDR 68,980,953 societal perspective. The costs of zoledronic acid therapy was IDR 87,694,119(SD:IDR 57,224,493) and cost of ibandronic acid therapy was IDR 106,856,703(SD:IDR 85,302,322). ICER per effectiveness was negative IDR 108,467,458 per 1 year time to SRE. Zoledronic acid was cost-effective (cost saving) against ibandronic acid. The implication of the results was that zoledronic acid was the best recommendation for bone metatase therapy so the further pharmacoeconomics analysis need to be done to other SRE preventive drugs to be included in the national formulary. Keywords: zoledronic acid, ibandronic acid, bone metastases, multiple myeloma, pharmacoeconomic

Kata Kunci : asam zoledronat, asam ibandronat, metastase tulang, multiple mieloma, farmakoekonomi