Bonaventura Clotet. HIV Unit & Retroviroloy Lab Univ Hosp Germans Trias i Pujol Badalona, Catalonia, Spain

Transcription

1 Cost-cutting measures to reduce the antiretroviral prescription bill under an urgent government requirement due to the economic crisis. A Spanish view. Bonaventura Clotet. HIV Unit & Retroviroloy Lab Univ Hosp Germans Trias i Pujol Badalona, Catalonia, Spain

2 Rationale. Spain is under a huge economic crisis that also (and particularly) involves the Public Health System. The Government spending on prescription drugs has been drastically reduced. The value of prescriptions in the hospital sector increased 55% from 2008 to 2011, and hospital-based expensive prescriptions have been identified as a special target for cost-cutting measures: Chemotherapy agents. Antiretrovirals (in Spain ARVs are supplied through Hospital pharmacies). Biologic agents. Others: PegIFN, anti-hep C antivirals, EPO, etc. HIV Units are forced to immediately reduce their antiretroviral budgets. Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis, Treatment Strategies & Antiviral Drug Resist. Barcelona (Spain), March, Invited lecture.

3 Rationale. Hospital-based drug costs. The current (end 2011) payment to pharma industries by gov. is delayed by an average of 525 days (>800 days in 4 Autonomous Communities). Spain's 18 regions owed pharmaceutical companies million in hospital-based drugs (a 36% increase vs 2010). Autonomous Community Debts (milion ) to pharma industry. Autonomous Community Median delay in payment to pahrma ind. * Only hospitals belonging to ICS * Only hospitals belonging to ICS Spanish Association for the Pharmaceutical Industry in Spain (FARMAINDUSTRIA). Available at: Accessed Feb 1, 2012.

4 Rationale. The case of an HIV Unit. In a 600 bed University-affiliated Hospital in Barcelona (Catalonia) a reference HIV Unit gives antiretroviral treatment to 2401 HIV-1-infected subjects. Antiretrovirals accounted for 47.8% of the overall hospital pharmacy budget (excluding Oncology): 17, (out of 37, , including treatments of hospitalized subjects) in Three main areas are identified in order to reduce the ARV budget: Inclusion of subjects into Clinical Trials (treatment payed by the trial). Reduction in the prize of ARV by pharma drug makers. Cost-cutting measures undertaken in patients receiving ART. Llibre JM. Pharmaeconomics & Outcomes Res in press

5 Methods. Analysis of cost-cutting measures (CCM) undertaken in HIV-1 patients receiving ART during a period of 6 months (May-Nov 2011). CCM defined as any change in ART leading to a costreduction in subjects successfully treated without toxicity, virological failure or any other reason to change the treatment. The HIV Unit has 14 treating physicians. Llibre JM. Pharmaeconomics & Outcomes Res in press

6 Results. Treatment changes undertaken. 673 total treatment changes undertaken during the period (187% increase vs the same period May-Nov in 2010). 28% of all the patients treated receive a treatment change. 378 (16% of overall cohort) subjects treated received a cost-cutting measure. Treatment change goal Month Cost ( ) N Percentage Cost-cutting measures ,80 378,00 56,17% Inclusion in Clinical Trials ,00 27,00 4,01% Ends a Clinical Trial 3.826,80 9,00 1,34% Toxicity ,50 76,00 11,29% Toxicity plus adherence or PK issues 1.406,70 2,00 0,30% Virological failure ,85 44,00 6,54% Others 8.100,00 31,00 4,61% Naives, news in the center or ART reinitiation ,60 64,00 9,51% PEP ,00 22,00 3,27% Total general ,85 673,00 100,00% Llibre JM. Pharmaeconomics & Outcomes Res in press

7 Llibre JM. Pharmaeconomics & Outcomes Res in press Results. Treatment changes undertaken. CCM: 412 treatment changes undertaken in 378 subjects switching their regimen to a less expensive treatment. ART Change N % of changes Truvada Kivexa DRV/r monotherapy LPV/r monotherapy NVP, switch to RAL substitution RAL withdrawal DRV/r dose reduction TCgen changes ATV/r 300/100 ATV ETR withdrawal or substitution Atripla, switches to MVC dose reduction or withdrawal Inactive NRTI withdrawal TPV withdrawal Others TOTAL %

8 Llibre JM. Pharmaeconomics & Outcomes Res in press Results. Treatment changes undertaken. CCM: 412 treatment changes undertaken in 378 subjects switching their regimen to a less expensive treatment. ART Change N % of changes Truvada Kivexa DRV/r monotherapy LPV/r monotherapy NVP, switch to RAL substitution RAL withdrawal DRV/r dose reduction TCgen changes ATV/r 300/100 ATV ETR withdrawal or substitution Atripla, switches to MVC dose reduction or withdrawal Inactive NRTI withdrawal TPV withdrawal Others TOTAL %

9 Llibre JM. Pharmaeconomics & Outcomes Res in press Results. CCM, total saved. TPV substitution Inactive NRTI withdr. 2% Switch to NVP 5% ATV/r ATV 1% DRV dose reduct. 4% MVC dose reduct. 2% 3TCgen (break FDC) MVC withdr. ETR substitution ETR withdr. 1% 0% 4% 3% Switch to Atripla 2% 1% 1% FPV dose reduct 2% Other 13% TVD to KVX Percentage of total savings ( ) achieved with every category of ARV change. (Total savings per month: ) DRV/r mono 23% 9% RAL substitution 15% RAL withdr 15% LPV/r mono

10 Results. Treatment changes undertaken. CCM: 412 treatment changes undertaken in 378 subjects switching their regimen to a less expensive treatment. Llibre JM. Pharmaeconomics & Outcomes Res in press

11 PI monotherapy Several randomised trials of PI monotherapy have been conducted Overall there has been a slight increase in the risk of low-level HIV RNA viraemia ( copies/ml), but no increase in the risk of drug resistance. Patients with increases in HIV RNA on PI monotherapy can be re-suppressed after intensifying with NRTIs

12 Randomised trials of PI monotherapy (simplification) Trial PI N Efficacy endpoint LPV/r: 7 trials, 710 patients OK pilot LPV/r 42 HIV RNA <500, Week 48, Switch included OK04 LPV/r 198 HIV RNA <500, Week 48, Switch included KALMO LPV/r 60 HIV RNA <80, Week 48 Cahn et al LPV/r 80 HIV RNA <200, Week 48, Switch included MOST LPV/r 60 HIV RNA in CSF Kalesolo LPV/r 220 HIV RNA <400, switch included KRETA LPV/r 50 Lipoatrophy DRV/r: 3 trials, 511 patients MONET DRV/r 256 HIV RNA <50, Week 48, Switch = failure MONOI DRV/r 225 HIV RNA <400, Week 48, Switch = failure MONARCH DRV/r 30 Cardiovascular Ongoing trials: 840 patients PROTEA DRV/r 250 HIV RNA <50, Week 48, switch = failure MRC PIVOT Any 590 Drug resistance, Week 192, ITT

13 MONET trial: HIV RNA by study visit (observed data) 100% Percentage of patients with HIV RNA: DRV/r + 2 NRTIs >1000 copies/ml copies/ml copies/ml <50 copies/ml 100% DRV/r 80% 80% 60% 60% 40% 40% 20% 20% 0% 0% SCR SCR Time on treatment - weeks Time on treatment - weeks

14 MONET Week 144 analysis: Outcome of HIV RNA elevations in DRV/r arm (21 patients) Patient HIV RNA blips Changed ARV / comments Last HIV RNA 1 140, 133 None / sinusitis <50 (wk 144) 2 59, 214 ZDV/3TC/NVP <50 (wk 144) 3 53,160 TDF/FTC/DRV/r <50 (wk 144) 4 132, 139 LPV/r mono <50 (wk 144) - local 5 539, 862 TDF/FTC/EFV <50 (wk 128) - local 6 75, 111 TDF/FTC/RAL <50 (wk 144) - local 7 215, 56 None / Poor adherence 50 (wk 144) 8 810, 605 TDF/FTC/DRV/r <50 (wk 144) , 628 None (stopped Rx) <50 (wk 144) , 100 None <50 (wk 144) , 60 ABC/3TC/DRV/r <50 (wk 144) , 79 None / Viral infection <50 (wk128) , 69 None 69 (wk 144) ,97 None / Poor adherence <50 (wk 144) 15 51, 80 None <50 (wk 96) , 106 TDF/FTC/DRV/r 231 (wk 112) , 157 TDF/FTC/DRV/r <50 (wk 96), 82 (wk 144?) , 288 TDF/FTC/DRV/r / Infection <50 (wk 144) , 6530 None <50 (wk 144) , 267 ABC/3TC/DRV/r / Infection <50 (wk 144) , 114 None <50 (wk 144)

15 PI monotherapy 5000 /year

16 PI monotherapy. Pending issues Neurocognitive impairment. Pilot studies have shown no differences between triple vs monotherapy Higher persistance of on going viral replication Shown by Buzon et al (2010) and Hatano et al (CROI 2013) RIPILM study on going Unknown clinical relevance

17 Results. CCM effect in the overall framework. Total savings ( ) achieved per month with every cost saving category.? * Median ARV pharma Industry discount during the period: 14.5%. Llibre JM. Pharmaeconomics & Outcomes Res in press

18 Results. CCM effect in the overall framework. Total savings ( ) achieved per month with every cost saving category. Overall savings: /month Pts on treat: 2401? * Median ARV pharma Industry discount during the period: 14.5%. Llibre JM. Pharmaeconomics & Outcomes Res in press

19 Conclusions Direct pharma industry discounts are the main source of savings in the antiretroviral budget in Spain. In an environment of deep economic crisis involving the public health system, CCM in ART can, to a lesser extent, reduce the antiretroviral budget as well. Changes to boosted PI monotherapy, ABC/Kivexa, NVP, and withdrawing or substituting expensive drugs whenever possible (RAL, ETR) account for 87% of the overall savings achieved with CCM. The 48-week efficacy and durability of these CCM is high, and a 48-week cost-effective analysis is on the way. Clinical trials with paid ART are also a significant source of saving (although transient).

20 CROI Atlanta 2013 Abstract 579

21 CROI Atlanta 2013 Abstract 579

22 ACKNOWLEDGEMENTS Josep M Llibre, Glòria Cardona, Xavier Bonafont, HIV Unit, Pharmacy Univ Hosp Germans Trias i Pujol Badalona, Barcelona

23 Bonaventura Clotet / Luis Menéndez-Arias Jonathan M. Schapiro / Daniel Kuritzkes David Burger / Jürgen Rockstroh Vicente Soriano / Amalio Telenti Francoise Brun-Vezinet / Anna Maria Geretti Charles A. Boucher / Douglas D. Richman Complete contents: Codes: GS-THEGUIDE1102 BMS-THEGUIDE2811 MSD-THEGUIDE2307

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