Monitoring Hepatitis C Treatment Uptake in Australia

Monitoring hepatitis C treatment uptake in Australia

Issue #8 December 20171

An estimated 43,360 individuals initiated direct acting Initiations of new antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection through Pharmaceutical Benefits Scheme (PBS) between March 2016 and June 2017, equating to 19% of treatment for the people living with chronic HCV infection in Australia. Of individuals initiating DAA treatment in this period, 66% chronic hepatitis were men, 54% were >50 years old, and 27% had cirrhosis. The most commonly prescribed regimen was sofosbuvir/ ledipasvir for 53%, followed by sofosbuvir+daclatasvir C from March for 39%. Of individuals initiated on sofosbuvir/ledipasvir, 16% were prescribed an 8-week course, 75% a 12-week course, and 10% a 24-week course. Of individuals initiated 2016 to June on sofosbuvir+daclatasvir, 67% were prescribed a 12-week course, and 33% a 24-week course. Overall, 57% of individuals 2017 were prescribed DAA treatment by specialists (46% by gastroenterologist, 7% by infectious diseases physicians, and 4% by other specialist), while 22% 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 39% in June 2017. Of individuals initiated on 8 weeks sofosbuvir/ledipasvir, 40% were prescribed treatment by specialists while 60% were prescribed treatment by non-specialists (34% by GPs). Of individuals prescribed on 24 weeks sofosbuvir/ledipasvir or 24 weeks sofosbuvir+daclatasvir, 69% were prescribed treatment by specialists while 31% were prescribed treatment by non-specialists (10% by GPs).

1. The Kirby Institute. Monitoring hepatitis C treatment uptake in Australia (Issue 8). The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia, December 2017 (available online at: https://kirby.unsw.edu.au/report/monitoring-hepatitis-c-treatment-uptake-australia-issue-8-december-2017). For more information, contact Professor Greg Dore ([email protected]) or Dr Behzad Hajari ([email protected]).

Issue #8 1 New treatments for chronic hepatitis C virus (HCV) Issue #8 newsletter provides data on: infection, named direct acting antiviral (DAA) • Uptake of DAA treatment through PBS-listing treatment, were listed on the Pharmaceutical Benefits between March 2016 and June 2017 by jurisdiction, Scheme (PBS): patients’ gender and age, treatment regimen, and • March 2016: Sofosbuvir/ledipasvir (Harvoni®), prescriber type sofosbuvir+daclatasvir (Sovaldi®+Daklinza®), • Proportion of individuals living with chronic HCV sofosbuvir+ribavirin (Sovaldi®+Ibavyr®), and infection and those with cirrhosis initiating DAA sofosbuvir+pegylated interferon-alfa-2a+ribavirin treatment between 2014 and June 2017 through PBS-listing (2016-17) and early DAA access (Sovaldi®+Pegasys®+ribavirin) avenues (2014-15). • May 2016: Paritaprevir/ritonavir/ ombitasvir+dasabuvir (Viekira PAK®) • January 2017: Elbasvir/grazoprevir (Zepatier®) • August 2017: Sofosbuvir/velpatasvir (Epclusa®)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) during March 2016 to June 2017, by jurisdiction.

19% 19% 18% 24% 16% 30% 25% 12%

16000 15000

14000 13000 12000 11000 10000 9000 8000 7000 6000

initiating treatment 5000 4000 3000 Estimated number of individuals 2000 1000 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

2. Data on sofosbuvir/velpatasvir were not included in this issue.

Issue #8 2 DAA treatment uptake Figure 2: Estimated proportion of individuals living with An estimated 43,360 individuals initiated DAA chronic HCV infection in Australia who initiated DAA treatment through PBS-listing between March 2016 treatment between 2014 and mid-2017, by liver fibrosis stage and June 2017 in Australia, including 15,470 in New 100% South Wales, 10,770 in Victoria, 8,400 in Queensland, Not-treated

2,780 in South Australia, 3,320 in Western Australia, 90% PBS (March 16 1,070 in Australian Capital Territory, 1,130 in - June 17) 80% Tasmania, and 430 in Northern Territory (Figure 1)3 Generic (2015)

70% Clinical Trials In 2015, an estimated 227,310 individuals were living (2014-15) with chronic HCV infection in Australia4, among whom 60% Pharmaceutical 19% initiated DAA treatment through PBS-listing company 50% between March 2016 and June 2017. This proportion compassionate access varied between 12% and 30% across jurisdictions 40% programs (Figure 1). (2014-15) 30% Between 2014 and mid-2017, an estimated 47,700 20% individuals, equating to 21% of the people living with chronic HCV infection in Australia, received DAA 10% treatment through PBS-listing, and early DAA access 0% avenues, including clinical trials, pharmaceutical F0-F3 F4 company compassionate access programs, and (n=207,130) (n=20,180) generic importation.

Among total population living with chronic HCV infection in Australia in 2015, an estimated 69% of those with cirrhosis (n=14,020) and 16% of those without cirrhosis (n=33,680) initiated DAA treatment up to June 2017 (Figure 2).

The monthly trends of DAA treatment uptake in Australia and in each jurisdiction are illustrated in Figure 3. After an initial decreasing trend, the monthly number of DAA initiation reached a relatively steady pattern from October 2016. The initial decline in treatment uptake was consistent with a “warehouse” effect with a large number of patients in specialist clinics awaiting DAA treatment access initiating treatment in the early months.

3. For an estimated 10 individuals, more than one jurisdiction was recorded. 4. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052

Issue #8 3 Figure 3: Estimated number of individuals initiating DAA treatment in each month during March 2016 to June 2017 in Australia (A), and by Jurisdiction (B and C)

5500 Figure 3A

5000 4500 4000 3500 3000 2500 2000 initiating treatment 1500

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

1800 Figure 3B NSW VIC 1600 QLD

1400

1200

1000

800

initiating treatment 600

400 Estimated number of individuals 200

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

350 Figure 3C SA WA ACT 300 TAS NT 250

200

150 initiating treatment 100

Estimated number of individuals 50

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

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

Issue #8 4 Gender and age distribution living with chronic HCV infection in Australia, a shift of individuals initiating DAA treatment towards older age groups was observed among those initiating DAA treatment (Figure 4). Of individuals initiating DAA treatment between March 2016 and June 2017, 66% were men and The age distribution of individuals initiating DAA 34% were women. treatment in each month showed a trend towards younger age groups from March to September 2016, Age distribution of individuals initiating DAA treatment while a relatively constant age distribution has been was similar between men and women (Figure 4). observed since then (Figure 5). An estimated 28% The highest proportion of total individuals were 51-60 of individuals initiating DAA treatment in March 2016 years old (37%), followed by 41-50 years old (25%). as opposed to 55% of those initiating DAA treatment Compared to the age distribution of the total population in June 2017 were ≤50 years old.

Figure 4: Age distribution of individuals living with chronic HCV infection in 2015 (dotted line) and those initiating DAA treatment during March 2016 to June 2017 (bars)

40% Men 35% Women 30% Estimated age 25% distribution of people living with chronic HCV infection in Australia 20%

15%

10%

0% <21 21-30 31-40 41-50 51-60 61-70 >70 Age group

Issue #8 5 Figure 5: Absolute frequency (A) and relative frequency (B) of age groups of individuals initiating DAA treatment in each month during March 2016 to June 2017

5500 Figure 5A ≤30

5000 31-40 4500 4000 41-50

3500 51-60 3000 ≥61 2500 2000 initiating treatment 1500

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

Figure 5B 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Mar 16 Apr 16 May 16 Jun 16 Jul 16 Aug 16 Sep 16 Oct 16 Nov 16 Dec 16 Jan 17 Feb 17 Mar 17 Apr 17 May 17 Jun 17

Distribution of DAA regimens prescribed Figure 6: Distribution of DAA regimens prescribed during for individuals initiating DAA treatment March 2016 to June 2017

The most commonly prescribed regimen was 3% 1% 4% sofosbuvir/ledipasvir±ribavirin for 53%, followed by SOF/LDV±RBV sofosbuvir+daclatasvir±ribavirin for 39%, elbasvir/ grazoprevir±ribavirin for 3%, and paritaprevir/ritonavir/ SOF+DCV±RBV ombitasvir+dasabuvir±ribavirin for 1%. For 4% of 39% EBR/GZR±RBV individuals, other DAA treatment regimens were prescribed (Figure 6). PrOD±RBV 53%

Other regimens

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

Issue #8 6 The breakdown of treatment initiation numbers by treatment regimen and treatment course duration Figure 7: Distribution of DAA regimens prescribed is shown in Figure 7. Of individuals initiated on during March 2016 to June 2017, by treatment regimen sofosbuvir/ledipasvir±ribavirin (n=22,920), 16% were and treatment course duration (16 weeks treatment exclusively applies to EBR/GZR+RBV) prescribed an 8-week course, 75% a 12-week course, and 10% a 24-week course. Of individuals initiated 24000 on sofosbuvir+daclatasvir±ribavirin (n=16,840), 16/24 weeks 67% were prescribed a 12-week course, and 33% 22000 12 weeks a 24-week course. Of individuals initiated on elbasvir/ 20000 grazoprevir±ribavirin (n=1,400), 97% were prescribed 18000 8 weeks a 12-week course, and 3% a 16-week course. 16000 Of individuals initiated on paritaprevir/ritonavir/ ombitasvir+dasabuvir±ribavirin (n=660), 83% 14000 were prescribed a 12-week course, and 17% 12000 a 24-week course. 10000 Sofosbuvir+daclatasvir is primarily prescribed for HCV 8000 genotype 3, with a 24-week course recommended 6000 for patients with cirrhosis and a 12-week course for 4000 those with no cirrhosis.5 Of total individuals initiated on sofosbuvir+daclatasvir, 67% were prescribed a Estimated number of patients initiating treatment 2000 12-week course, and 33% a 24-week course. 0 SOF/ SOF+DCV EBR/ PrOD LDV±RBV ±RBV GZR±RBV ±RBV It was estimated that 27% of total individuals initiating DAA treatment between March 2016 and June 2017 SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; had cirrhosis. GZR: Grazoprevir; PrOD: Paritaprevir/ritonavir/Ombitasvir+Dasabuvir; RBV: Ribavirin The monthly proportion of 24-week courses to the total prescriptions of sofosbuvir+daclatasvir is shown in Figure 8. The proportion of 24-week courses of relatively steady pattern observed since then. In June sofosbuvir+daclatasvir prescriptions decreased from 2017, 27% of sofosbuvir+daclatasvir prescriptions 45% in March to 24% in November 2016 with a included a 24-week course treatment.

Figure 8: Proportion of individuals initiated 12 weeks versus 24 weeks sofosbuvir+daclatasvir regimen in each month during March 2016 to June 2017

100% SOF+DCV±RBV (12 weeks) 90% SOF+DCV±RBV 80% (24 weeks) 70% 60% 50% 40% 30% 20% SOF: Sofosbuvir; 10% DCV: Daclatasvir; RBV: Ribavirin 0% Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun 16 16 16 16 16 16 16 16 16 16 17 17 17 17 17 17

5. Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement (August 2017). Gastroenterological Society of Australia, Melbourne, Australia, 2017.

Issue #8 7 Distribution of health care providers Territory, 22% of individuals were prescribed DAA prescribing for individuals initiating treatment by infectious disease physicians, compared DAA treatment to 4% by gastroenterologists. In Western Australia, 26% of individuals were prescribed DAA treatment by The majority of individuals initiating DAA treatment GPs, compared to 18% by gastroenterologists. Across received their prescriptions from gastroenterologists jurisdictions, the proportion of individuals prescribed (46%), followed by general practitioners (GPs; DAA treatment by GPs was highest in Tasmania (37%), 22%), infectious diseases physicians (7%), and Queensland (27%), and Western Australia (26%). other specialists (4%). Twenty percent of individuals received their prescriptions from other physicians, The distribution of prescriber types in each month including supervised medical officers (e.g., interns, is shown in Figure 10. The proportion of individuals resident medical officers, and registrars), public prescribed DAA treatment by GPs increased from health physicians, temporary resident doctors, 8% in March 2016 to 39% in June 2017. Increasing and non-vocationally registered doctors (Figure 9). contribution of GPs in DAA prescribing is also evident Overall, 57% of individuals received their prescriptions by increasing the absolute number of individuals from specialists. initiated on DAA treatment by GPs, from 410 in March 2016 to 670 in June 2017. Distribution of prescriber types varied across jurisdictions (Figure 9). Gastroenterologists were the prominent prescriber in most jurisdictions. In Northern

Figure 9: Distribution of prescriber types for individuals initiating DAA treatment during March 2016 to June 2017, 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

Other physicians included supervised medical officers (e.g., interns, resident medical officers, and registrars), public health physicians, temporary resident doctors, and non-vocationally registered doctors.

Issue #8 8 Figure 10: Absolute frequency (A) and relative frequency (B) of prescriber types in each month for individuals initiating DAA treatment during March 2016 to June 2017 in Australia

5500 Figure 10A 5000 4500 4000 Other 3500 physicians

3000 General 2500 Practitioners 2000 Other Specialists 1500 Infectious Diseases 1000 Physicians 500 Gastroenterologists 0 Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun 16 16 16 16 16 16 16 16 16 16 17 17 17 17 17 17

Figure 10B 100% 90% 80% 70% 60% Other physicians 50% included supervised medical officers 40% (e.g., interns, resident medical officers, and 30% registrars), public health 20% physicians, temporary resident doctors, 10% and non-vocationally registered doctors. 0% Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun 16 16 16 16 16 16 16 16 16 16 17 17 17 17 17 17

Distribution of prescribed DAA regimens weeks sofosbuvir/ledipasvir prescriptions, 74% was by prescription type by specialists compared to 8% by GPs. Similarly, of the total number of 24 weeks sofosbuvir+daclatasvir The distribution of prescribed DAA regimens by prescriptions, 67% was by specialists compared to prescriber type is shown in Figure 11. Across all 11% by GPs (Figure 11B). These two regimens are prescriber types, the most commonly prescribed primarily prescribed for patients with cirrhosis.6 regimens included 12 weeks sofosbuvir/ledipasvir, followed by 12 weeks sofosbuvir+daclatasvir Across all prescriber types, the highest proportion (Figure 11A). of 8 weeks sofosbuvir/ledipasvir regimen was observed in prescriptions by GPs (13%, Figure 11A). Of prescriptions by specialists, 7% included 24 Of the total number of 8 weeks sofosbuvir/ledipasvir weeks sofosbuvir/ledipasvir and 15% included 24 prescriptions, the majority (34%) was by GPs. This weeks sofosbuvir+daclatasvir. These proportions regimen is prescribed for treatment-naïve patients were 2% and 6%, respectively, among prescriptions with genotype 1, no cirrhosis, and pre-treatment by GPs (Figure 11A). Of the total number of 24 HCV RNA<6 million IU/mL.6

6. Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement (August 2017). Gastroenterological Society of Australia, Melbourne, Australia, 2017

Issue #8 9 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 March 2016 to June 2017 in Australia

Figure 11A

100% Other regimens 90% SOF+DCV±RBV 24 wk 80%

70% SOF+DCV±RBV 12 wk 60% SOF/LDV±RBV 24 wk 50%

40% SOF/LDV±RBV 12 wk 30% SOF/LDV 8 wk 20% 10% 0% Gastro- Infectious Other General Other 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±RBV SOF/LDV±RBV SOF+DCV±RBV SOF+DCV±RBV Other 8 wk 12 wk 24 wk 12 wk 24 wk Regimens

Issue #8 10 Methodology adjusted, using REACH-C Study data of 24 weeks sofosbuvir+daclatasvir prescribed for those without The following data sources were used for analysis: cirrhosis (25% of prescriptions) and 12 weeks • The data of a longitudinal cohort of individuals, sofosbuvir+daclatasvir prescribed for those with representing a 10% random sample of the PBS cirrhosis (3% of prescriptions). Then, the adjusted database were used to estimate the number of proportion was extrapolated to the total DAA initiations individuals initiating DAA between March 2016 during March 2016 to June 2017 to estimate the and June 2017, and for all sub-group analyses DAA treatment uptake among individuals with of DAA treatment uptake. cirrhosis. More details of the methods for the • Real world Efficacy of Antiviral therapy in Chronic estimations have been described elsewhere.11 Hepatitis C (REACH-C Study) is an observational study with the data being collected from a national There are some considerations to be taken into network of eleven diverse clinical services including account for interpreting the results. Given that the specialist viral hepatitis clinics, general practice, results are extrapolated from 10% random sample sexual health, community and drug and alcohol of the PBS database, the results in subgroups with centres.7 REACH-C Study data was used to adjust small numbers might be subject to uncertainties. the proportion of sofosbuvir+daclatasvir regimens This analysis provided data of treatment initiations. prescribed for patients with cirrhosis. It does not reflect the number of individuals who completed their treatment course, although treatment • The data from DAA clinical trials and discontinuation is expected to be low. The jurisdiction- compassionate access programs were collected specific treatment initiation estimates in this report are from pharmaceutical companies. based on data of dispensing pharmacy location, and • The estimated number of individuals receiving not patient’s residence location while the estimated generic DAA was based on the data of FixHepC numbers of individuals living with chronic HCV are (http://fixhepc.com/), a web-based platform which based in part on the number of HCV notifications facilitates generic DAA personal importation. which are reported based on residence. Thus • The estimated numbers of individuals living with cross-jurisdiction dynamics should be considered chronic HCV infection and cirrhosis in Australia in in interpreting the jurisdiction-specific data. It could 2015 were extracted from a modelling study.8 have more impact on the estimates from smaller jurisdictions given their smaller population as the The number of individuals with cirrhosis initiating DAA denominator. The data of sofosbuvir+daclatasvir treatment was estimated. Among individuals initiating regimen was the basis of estimating number of DAA treatment through early access avenues in individuals with cirrhosis initiating DAA treatment 2014 and 2015, it was assumed that 25% of those through PBS-listing. This regimen was primarily in clinical trials, 95% of those in compassionate prescribed for genotype 3, which has been associated access programs, and 30% of those receiving with more rapid liver fibrosis progression.12 Thus, 9 generic DAA had cirrhosis. Sofosbuvir+daclatasvir our estimation of DAA treatment uptake among regimen has been recommended for HCV genotype those with cirrhosis could be potentially subject to an 10 3 (cirrhosis - 24 weeks; no cirrhosis - 12 weeks). overestimation. The assumed proportion of individuals Among individuals initiating DAA treatment through with cirrhosis among those accessed DAA treatment PBS-listing, the proportion of those initiating a through clinical trials and compassionate access 24-week course of sofosbuvir+daclatasvir to the programs were based on expert opinion. total sofosbuvir+daclatasvir initiations was initially

7. The Kirby Institute. Real world efficacy of antiviral therapy in chronic hepatitis C inAustralia (Issue 1). The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia, July 2017 (available online at: https://kirby.unsw.edu.au/report/real-world-efficacy-antiviral-therapy-chronic-hepatitis-caustralia-issue-1-july-2017) 8. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052 9. Freeman JA, Sallie R, Kennedy A, Jeffreys G, Savage A, Hill AM. High sustained virological response rates using legally imported, generic direct acting antiviral treatment for hepatitis C. Hepatology 2016; 63(1 SUPP): 444A 10. Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C virus infection: a consensus statement (August 2017). Gastroenterological Society of Australia, Melbourne, Australia, 2017 11. 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 2017 [in press]. 12. Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nature Review Gastroenterology Hepatology 2013; 10(9): 553-62.

Issue #8 11