Monitoring Hepatitis C Treatment Uptake in Australia

Monitoring hepatitis C treatment uptake in Australia

Issue #10 June 20191

An estimated 74,600 individuals initiated direct acting antiviral (DAA) Initiations of treatment for chronic hepatitis C virus (HCV) infection in Australia, including 70,260 individuals through Pharmaceutical Benefits Scheme (PBS) during 2016 to 2018, and 4,340 individuals through early DAA new treatment access avenues in 2014 and 2015. It is estimated that 33% of the people living with chronic HCV infection in Australia initiated DAA treatment. for chronic Of individuals initiating DAA treatment during 2016 to 2018 (n=70,260), 67% were men, and 51% were 50 years old or younger. hepatitis C The proportion of individuals ≤50 years old initiating treatment increased from 28% in March 2016 to 67% in the last quarter of 2018. from 2016 The most commonly prescribed regimen was sofosbuvir/ledipasvir for 39%, followed by sofosbuvir+daclatasvir for 27%, and sofosbuvir/velpatasvir for 23%. Since August 2018 when both to 2018 pan-genotypic regimens were available (i.e., sofosbuvir/velpatasvir and glecaprevir/pibrentasvir), 53% of individuals have been initiated on sofosbuvir/velpatasvir, 32% on glecaprevir/pibrentasvir, and 15% on other regimens.

Overall, 49% of individuals have been prescribed DAA treatment by specialists (39% by gastroenterologist, 7% by infectious diseases physicians, and 3% by other specialist), while 29% of individuals were prescribed DAA treatment by general practitioners (GPs). The proportion of individuals prescribed DAA treatment by GPs increased from 8% in March 2016 to 41% in the last quarter of 2017, followed by a relatively constant trend in 2018. Among individuals initiating DAA treatment in 2018, 39% were initiated on treatment by GPs, and 33% by specialists.

1. The Kirby Institute. Monitoring hepatitis C treatment uptake in Australia (Issue 10). The Kirby Institute, UNSW Sydney, NSW, Australia, June 2019 (available online at: https://kirby.unsw.edu.au/report/monitoring-hepatitis-c-treatment-uptake-australia-issue-10-june-2019). For more information, contact Dr Behzad Hajari ([email protected]) or Professor Greg Dore ([email protected]).

Issue #10 1 New treatments for chronic hepatitis C virus (HCV) DAA treatment uptake infection, named direct acting antiviral (DAA) An estimated 70,260 individuals initiated DAA treatment, were listed on the Pharmaceutical treatment through the PBS between March 2016 and Benefits Scheme (PBSS): December 2018 in Australia. In 2014 and 2015, prior ® • March 2016: Sofosbuvir/ledipasvir (Harvoni ), to DAA regimens being listed on PBS, an estimated ® ® sofosbuvir+daclatasvir (Sovaldi +Daklinza ), 4,340 individuals received DAA treatment through ® ® sofosbuvir+ribavirin (Sovaldi +Ibavyr ), and early DAA access avenues, including clinical trials, sofosbuvir+pegylated interferon-alfa-2a+ribavirin pharmaceutical company compassionate access ® ® (Sovaldi +Pegasys +ribavirin) programs, and generic importation.2 Considering • May 2016: Paritaprevir/ritonavir/ this number, an overall estimated number of 74,600 ombitasvir+dasabuvir (Viekira PAK®) individuals received DAA treatment from 2014 to 2018. • January 2017: Elbasvir/grazoprevir (Zepatier®) In 2015, an estimated 227,310 individuals were living ® • August 2017: Sofosbuvir/velpatasvir (Epclusa ) with chronic HCV infection in Australia.3 Given the • August 2018: Glecaprevir/pibrentasvir (Maviret®) overall treatment initiation in 74,600 individuals, an • April 2019: Sofosbuvir/velpatasvir/voxilaprevir estimated 33% of individuals living with chronic HCV (Vosevi®) infection in Australia, initiated DAA treatment between 2014 and 2018. Issue #10 newsletter provides data on monthly uptake of DAA treatment through PBS-listing between March At jurisdictional level, the number of individuals initiating 2016 and December 2018 by jurisdiction, patients’ DAA treatment through the PBS between March 2016 gender and age, treatment regimen, and prescriber and December 2018 included 24,510 in New South type. The data of sofosbuvir/velpatasvir/voxilaprevir Wales, 17,750 in Victoria, 13,830 in Queensland, 4,580 have not been provided in this issue given this in South Australia, 5,780 in Western Australia, 1,410 regimen was listed on PBS in 2019. in Australian Capital Territory, 1,720 in Tasmania, and 700 in Northern Territory.4 The estimated proportion of individuals living with chronic HCV infection initiating DAA treatment in this period varied between 19% to 39% across jurisdictions (Figure 1).

Among 70,260 individuals initiating DAA treatment through the PBS during 2016 to 2018, an estimated 2,920 individuals (4.1%) received more than one DAA treatment course. DAA retreatment could be related to response failure to the first DAA treatment (including early treatment discontinuation), or HCV reinfection after successful treatment.

2. Hajarizadeh B, Grebely J, Matthews GV, Martinello M, Dore GJ. Uptake of direct acting antiviral treatment for chronic hepatitis C in Australia. Journal of Viral Hepatitis 2018; 25(6): 640-8 3. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052 4. For a small number of individuals (n=10 to 20), more than one jurisdiction were recorded.

Issue #10 2 Figure 1: The estimated number of individuals initiating DAA treatment (bar charts) and the proportion of individuals living with chronic HCV infection who initiated DAA treatment (pie charts) between 2016 and 2018, by jurisdiction

30% 32% 29% 39% 28% 39% 38% 19%

25000

22500

20000

17500

15000

12500

10000 initiating treatment 7500

Estimated number of individuals 5000

2500

0 NSW VIC QLD SA WA ACT TAS NT

NSW: New South Wales; VIC: Victoria; QLD: Queensland; SA: South Australia; WA: Western Australia; ATC: Australian Capital Territory; TAS: Tasmania; NT: Northern Territory

The monthly trends of DAA treatment uptake in Australia and in each jurisdiction are illustrated in Figure 2. In 2016, 2017, and 2018, respectively 32,610, 21,540, and 16,110 individuals initiated DAA treatment. A modelling study indicated that 17,100 treatment initiations in 2018 and an annual 13,680 treatment initiations from 2019 onward are required to put Australia on track to achieve WHO HCV elimination targets of treating 80% of people living with HCV and 80% reduction in HCV incidence by 2030.5 The treatment uptake in 2018 was slightly lower than that required.

5. Kwon JA, Dore GJ, Grebely J, et al. Australia on track to achieve WHO HCV elimination targets following rapid initial DAA treatment uptake: A modelling study. Journal of Viral Hepatitis 2019; 26(1): 83-92.

Issue #10 3 Figure 2: Estimated number of individuals initiating DAA treatment in each month during 2016 to 2018 in Australia (A), and by Jurisdiction (B and C)

5500 Figure 2A

5000 4500 4000 3500 3000 2500 2000 initiating treatment 1500

Estimated number of individuals 1000 500 0 Jul 16 Jul 17 Jul 18 Oct 16 Oct 17 Oct 18 Apr 16 Apr 17 Apr 18 Jun 16 Jan 17 Jun 17 Jan 18 Jun 18 Mar 16 Mar 17 Mar 18 Feb 17 Feb 18 Nov 16 Dec 16 Nov 17 Dec 17 Nov 18 Dec 18 Aug 16 Sep 16 Aug 17 Sep 17 Aug 18 Sep 18 May 16 May 17 May 18

1800 Figure 2B NSW VIC 1600 QLD

1400

1200

1000

800

initiating treatment 600

400 Estimated number of individuals 200

0 Jul 16 Jul 17 Jul 18 Oct 16 Oct 17 Oct 18 Apr 16 Apr 17 Apr 18 Jun 16 Jan 17 Jun 17 Jan 18 Jun 18 Mar 16 Mar 17 Mar 18 Feb 17 Feb 18 Nov 16 Dec 16 Nov 17 Dec 17 Nov 18 Dec 18 Aug 16 Sep 16 Aug 17 Sep 17 Aug 18 Sep 18 May 16 May 17 May 18

350 Figure 2C SA WA ACT 300 TAS NT 250

200

150 initiating treatment 100

Estimated number of individuals 50

NSW: New South Wales; VIC: Victoria; QLD: Queensland; SA: South Australia; WA: Western Australia; ATC: Australian Capital Territory; TAS: Tasmania; NT: Northern Territory

Issue #10 4 Distribution of DAA regimens prescribed 2017 and August 2018, respectively. During August for individuals initiating treatment 2017 to July 2018, Sofosbuvir/velpatasvir was the most commonly prescribed regimen (67%). Since August Overall, the most commonly prescribed regimen 2018, 53% of individuals initiating DAA have been was sofosbuvir/ledipasvir±ribavirin for 39%, followed prescribed sofosbuvir/velpatasvir, 32% have been by sofosbuvir+daclatasvir±ribavirin for 27%, and prescribed glecaprevir/pibrentasvir, and 15% have sofosbuvir/velpatasvir for 23%. Sofosbuvir/velpatasvir been initiated on other regimens (Figures 3 and 4). and glecaprevir/pibrentasvir were PBS listed on August

Figure 3: Distribution of DAA regimens prescribed during 2016 to 2018 (overall), January to July 2017 (seven months prior to SOF/VEL being PBS listed), August 2017 to July 2018 (before GLE/PIB being PBS listed), and August to December 2018

100% GLE/PIB 90% SOF/VEL 80% EBR/GZR±RBV 70% 60% PrOD±RBV

50% SOF+Others 40% SOF+DCV±RBV 30% SOF/LDV±RBV 20% 10% 0% TOTAL January 2017 August 2017 August 2018 to to July 2017 to July 2018 December 2018

SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; GZR: Grazoprevir; PrOD: Paritaprevir/ritonavir/Ombitasvir+Dasabuvir; VEL: Velpatasvir; GLE: Glecaprevir; PIB: Pibrentasvir RBV: Ribavirin

Issue #10 5 Figure 4: Absolute frequency (A) and relative frequency (B) of DAA regimens prescribed for individuals initiating DAA treatment in each month during 2016 to 2018

GLE/PIB

SOF/VEL 5500 Figure 4A

5000 EBR/GZR±RBV

4500 PrOD±RBV

4000 SOF+Others 3500 SOF+DCV±RBV 3000 SOF/LDV±RBV 2500 2000 initiating treatment 1500

Figure 4B 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Jul 16 Jul 17 Jul 18 Oct 16 Oct 17 Oct 18 Apr 16 Apr 17 Apr 18 Jun 16 Jan 17 Jun 17 Jan 18 Jun 18 Mar 16 Mar 17 Mar 18 Feb 17 Feb 18 Nov 16 Dec 16 Nov 17 Dec 17 Nov 18 Dec 18 Aug 16 Sep 16 Aug 17 Sep 17 Aug 18 Sep 18 May 16 May 17 May 18

The breakdown of treatment initiation numbers by grazoprevir±ribavirin (n=3,990), 96% were prescribed treatment regimen and treatment course duration a 12-week course, and 4% a 16-week course. Of is shown in Figure 5. Of individuals initiated on individuals initiated on glecaprevir/pibrentasvir sofosbuvir/ledipasvir±ribavirin (n=27,050), 19% were (n=2,090), 78% were prescribed an 8-week course, prescribed an 8-week course, 72% a 12-week course, 17% a 12-week course, and 5% a 16-week course. and 9% a 24-week course. Of individuals initiated Sixteen weeks glecaprevir/pibrentasvir is prescribed on sofosbuvir+daclatasvir±ribavirin (n=18,720), for individuals with a response failure to a previous 69% were prescribed a 12-week course, and 31% a DAA treatment. 24-week course. Of individuals initiated on elbasvir/

Issue #10 6 Figure 5: Absolute frequency (A) and relative frequency (B) of DAA regimens prescribed during 2016 to 2018, by treatment regimen and treatment course duration

Figure 5A Figure 5B

28000 100% 16/24 weeks 26000 90% 24000 12 weeks 22000 80% 8 weeks 20000 70% 18000 60% 16000 14000 50% 12000 40% 10000 8000 30%

6000 20% 4000 10% Estimated number of patients initiating treatment 2000 0 0% SOF/ SOF+ SOF/ EBR/ GLE/ SOF/ SOF+ SOF/ EBR/ GLE/ LDV± DCV± VEL GZR± PIB LDV± DCV± VEL GZR± PIB RBV RBV RBV RBV RBV RBV

SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; GZR: Grazoprevir; PrOD: Paritaprevir/ritonavir/Ombitasvir+Dasabuvir; VEL: Velpatasvir; RBV: Ribavirin

Figure 6: Quarterly gender distribution of individuals initiating DAA treatment during 2016 to 2018 Men Women

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% March Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2016 2016 2016 2016 2017 2017 2017 2017 2018 2018 2018 2018

Issue #10 7 Gender and age distribution of individuals initiating DAA treatment Figure 7: Age distribution of individuals living with chronic HCV infection in 20156 (dotted line) and those Of individuals initiating DAA treatment between 2016 initiating DAA treatment during 2016 to 2018 (bars) and 2018, 67% were men and 33% were women. The proportion of women decreased slightly over time, 40% from 36% in March 2016 to 28% in the last quarter of 35% 2018 (Figure 6). 30% Age distribution of individuals initiating DAA treatment was similar between men and women (Figure 7). 25% The highest proportion of individuals were 51-60 years (33%), followed by 41-50 years (26%). An overall 20%

48% were older than 50 years. Compared to the age 15% distribution of the total population living with chronic HCV infection in Australia in 2015, a shift towards 10% older age groups was observed among those initiating 5% DAA treatment (Figure 7). This shift, however, is decreasing given that a trend towards younger age 0% groups is observed over time. The proportion of <21 21-30 31-40 41-50 51-60 61-70 >70 individuals ≤50 years initiating treatment increased Age group from 28% in March 2016 to 67% in the last quarter Men Women Estimated age of 2018 (Figure 8). distribution of people living with chronic HCV infection in Australia

Figure 8: Quarterly age distribution of individuals initiating DAA treatment during 2016 to 2018

100% ≤30 90% 31-40 80% 41-50 70% 60% 51-60

50% ≥61 40% 30% 20% 10% 0% March Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2016 2016 2016 2016 2017 2017 2017 2017 2018 2018 2018 2018

6. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052

Issue #10 8 Distribution of health care providers Distribution of prescriber types varied across prescribing for individuals initiating jurisdictions (Figure 9). In all jurisdictions, expect for DAA treatment Victoria, specialists initiated DAA treatment for less than 50% of individuals. Across jurisdictions, the Among individuals initiating DAA treatment during proportion of individuals initiated on DAA treatment 2016 to 2018, the majority received their prescriptions by GPs was highest in Queensland (37%), Tasmania from gastroenterologists (39%), followed by general (35%), and Western Australia (34%). practitioners (GPs; 29%), infectious diseases physicians (7%), and other specialists (3%). Twenty- The distribution of prescriber types in each quarter two percent of individuals received their prescriptions is shown in Figure 10. The proportion of individuals from other physicians, including supervised medical prescribed DAA treatment by GPs increased from officers (e.g., interns, resident medical officers, and 8% in March 2016 to 41% in the last quarter of 2017, registrars), public health physicians, temporary resident followed by a relatively constant trend in 2018. Among doctors, other/unclassified non-specialist and undefined individuals initiating DAA treatment in 2018, 39% were (Figure 9). Overall, 49% of individuals received their initiated on treatment by GPs, 33% by specialists, and prescriptions from specialists. 28% by other physicians.

Figure 9: Distribution of prescriber types for individuals initiating DAA treatment during 2016 to 2018, in Australia and by jurisdiction

100% Other physicians 90% General 80% Practitioners 70% Other Specialists 60% Infectious Diseases 50% Physicians

40% Gastroenterologists 30% 20% 10% 0% Australia NSW VIC QLD SA WA ACT TAS NT

Issue #10 9 Figure 10: Quarterly distribution of prescriber types for individuals initiating DAA treatment during 2016 to 2018

100% Other physicians 90% General 80% Practitioners 70% Other Specialists 60% Infectious Diseases 50% Physicians

40% Gastroenterologists 30% 20% 10% 0% March Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2016 2016 2016 2016 2017 2017 2017 2017 2018 2018 2018 2018

Distribution of prescribed DAA Across all prescriber types, the highest proportion of regimens by prescriber type 8 weeks treatment (i.e., 8 weeks sofosbuvir/ledipasvir and 8 weeks glecaprevir/pibrentasvir) was observed The distribution of prescribed DAA regimens by in prescriptions by GPs and other non-specialist prescriber type is shown in Figure 11. Among all physicians (12% and 13%, respectively; Figure specialist groups, the most commonly prescribed 11A). Of the total number of prescriptions of 8 weeks regimen included 12 weeks sofosbuvir/ledipasvir treatment, 37% were by GPs and 34% by specialists (31-34%), while among GPs the most commonly (Figure 11B). This regimen is prescribed for treatment- prescribed regimen included sofosbuvir/velpatasvir naïve patients with no cirrhosis. (27%; Figure 11A). Of the total number of sofosbuvir/velpatasvir Of prescriptions by specialists, 17% included an prescriptions, the proportions by specialists and GPs extended duration regimen (i.e., 24 weeks sofosbuvir/ were comparable with 37% prescribed by specialist ledipasvir, 24 weeks sofosbuvir+daclatasvir, 16 weeks (28% by Gastroenterologists), and 34% by GPs elbasvir/grazoprevir, and 12-16 weeks glecaprevir/ (Figure 11B). pibrentasvir), compared to 6% of prescriptions by GPs (Figure 11A). Of the total number of prescriptions of extended duration regimens, 68% were by specialists compared to 13% by GPs (Figure 11B). These regimens are primarily prescribed for patients with cirrhosis, or those with DAA treatment failure.

Issue #10 10 Figure 11: Distribution of prescribed DAA regimens by prescriber types (A) and distribution of prescriber types by prescribed DAA regimens (B) for individuals initiating DAA treatment during 2016 to 2018

Figure 11A Other regimens

100% GLE/PIB 16 wk

90% GLE/PIB 12 wk

80% GLE/PIB 8 wk

70% EBR/GZR 12 wk 60% EBR/GZR 16 wk 50% SOF/VEL 12 wk 40% SOF+DCV 24 wk 30% SOF+DCV 12 wk 20% SOF/LDV 24 wk 10% SOF/LDV 12 wk 0% Gastro- Infectious Other General Other SOF/LDV 8 wk enterologists Diseases Specialists Practitioners Physicians Physicians

Figure 11B

100% Other physicians 90% General 80% Practitioners 70% Other Specialists 60% Infectious Diseases 50% Physicians

40% Gastroenterologists 30% 20% 10% 0% SOF/LDV SOF/LDV SOF/LDV SOF+DCV SOF+DCV SOF/VEL EBR/GZR EBR/GZR GLE/PIB GLE/PIB 8 wk 12 wk 24 wk 12 wk 24 wk 12 wk 16 wk 12 wk 8 wk 12-16 wk

Other physicians included supervised medical officers (e.g., interns, resident medical officers, and registrars), public health physicians, temporary resident doctors, other/unclassified non-specialist and undefined. SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; GZR: Grazoprevir; VEL: Velpatasvir; GLE: Glecaprevir; PIB: Pibrentasvir

Issue #10 11 Methodology There are some factors that should be considered in interpreting the results. Given that the results The methods for the estimations have been described are extrapolated from 10% random sample of the in detail elsewhere.7 In brief, the following data PBS database, the results in subgroups with small sources were used for analysis: numbers might be subject to uncertainties. This • The data of a longitudinal cohort of individuals, analysis provided data of treatment initiations. It does representing a 10% random sample of the PBS not reflect the number of individuals who completed database were used to estimate the number of their treatment course, although early treatment individuals initiating DAA between March 2016 and discontinuation is expected to be low. The jurisdiction- December 2018, and for all sub-group analyses of specific treatment initiation estimates in this report are DAA treatment uptake. based on data of dispensing pharmacy location, and • The estimated numbers of individuals living with not patient’s residence location while the estimated chronic HCV infection in Australia and in each numbers of individuals living with chronic HCV are jurisdiction in 2015, and age distribution among based in part on the number of HCV notifications individuals living with chronic HCV infection were which are reported based on residence. Thus extracted from a modelling study.8 cross-jurisdiction dynamics should be considered in interpreting the jurisdiction-specific data. It could have more impact on the estimates from smaller jurisdictions given their smaller population as the denominator.

7. Hajarizadeh B, Grebely J, Matthews GV, Martinello M, Dore GJ. Uptake of direct acting antiviral treatment for chronic hepatitis C in Australia. Journal of Viral Hepatitis 2018; 25(6): 640-8. 8. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052

Issue #10 12