Monitoring hepatitis C treatment
uptake in Australia Issue #9 July 20181
Initiations of new treatment for chronic hepatitis C from March 2016 to March 2018
An estimated 58,280 individuals initiated direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection through Pharmaceutical Benefits Scheme (PBS) between March 2016 and March 2018, equating to 26% of the people living with chronic HCV infection in Australia. Of individuals initiating DAA treatment in this period, 67% were men, and 51% were >50 years old. The most commonly prescribed regimen was sofosbuvir/ ledipasvir for 45%, followed by sofosbuvir+daclatasvir for 32%, and sofosbuvir/velpatasvir for 14%. Since sofosbuvir/ velpatasvir was listed in August 2017, it has been the most commonly prescribed regimen with 64% of individuals initiating DAA treatment from August 2017 to March 2018 prescribed sofosbuvir/velpatasvir. Of individuals initiated on sofosbuvir/velpatasvir, 40% were prescribed treatment by a specialist while 60% were prescribed treatment by non-specialists (30% by GPs). Overall, 52% of individuals have been prescribed DAA treatment by specialists (42% by gastroenterologist, 7% by infectious diseases physicians, and 4% by other specialist), while 27% 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 40% in May 2017, followed by a relatively constant trend since then. During the first three months of 2018 (January to March), 38% of individuals initiating DAA treatment were prescribed treatment by GPs.
1. The Kirby Institute. Monitoring hepatitis C treatment uptake in Australia (Issue 9). The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia, July 2018 (available online at: https://kirby.unsw.edu.au/report/monitoring-hepatitis-c-treatment-uptake-australia-issue-9-july-2018). For more information, contact Professor Greg Dore (gdore@kirby.unsw.edu.au) or Dr Behzad Hajari (bhajarizadeh@kirby.unsw.edu.au).
Issue #9
1
New treatments for chronic hepatitis C virus (HCV) infection, named direct acting antiviral (DAA) treatment, were listed on the Pharmaceutical Benefits Scheme (PBS):
in New South Wales, 14,670 in Victoria, 11,340 in Queensland, 3,790 in South Australia, 4,560 in Western Australia, 1,220 in Australian Capital Territory, 1,500 in Tasmania, and 610 in Northern Territory (Figure 1).2
• March 2016: Sofosbuvir/ledipasvir (Harvoni®), sofosbuvir+daclatasvir (Sovaldi®+Daklinza®), sofosbuvir+ribavirin (Sovaldi®+Ibavyr®), and sofosbuvir+pegylated interferon-alfa-2a+ribavirin (Sovaldi®+Pegasys®+ribavirin)
In 2015, an estimated 227,310 individuals were living with chronic HCV infection in Australia,3 among whom 26% initiated DAA treatment between March 2016 and March 2018. This proportion varied between 17% and 34% across jurisdictions (Figure 1).
• May 2016: Paritaprevir/ritonavir/ ombitasvir+dasabuvir (Viekira PAK®)
In 2014 and 2015, prior to DAA regimens being listed on PBS, an estimated 4,340 individuals received DAA treatment through early DAA access avenues, including clinical trials, pharmaceutical company compassionate access programs, and generic importation. Considering this number, an overall estimated number of 62,620 individuals, equating to 28% of the people living with chronic HCV infection in Australia, received DAA treatment from 2014 to March 2018.
• January 2017: Elbasvir/grazoprevir (Zepatier®) • August 2017: Sofosbuvir/velpatasvir (Epclusa®) Issue #9 newsletter provides data on: • Monthly uptake of DAA treatment through PBS-listing between March 2016 and March 2018 by jurisdiction, patients’ gender and age, treatment regimen, and prescriber type • Proportion of individuals living with chronic HCV infection initiating DAA treatment through PBS-listing (2016-18) and early DAA access avenues (2014-15).
The monthly trends of DAA treatment uptake in Australia and in each jurisdiction are illustrated in Figure 2. After an initial decreasing trend, the monthly number of DAA initiation reached a relatively steady pattern from December 2016 through October 2017. There have been further declines in DAA initiations in 2018, with the monthly number during January to March 2018 less than 1,500 (about 600 initiations per month less than the equivalent period in 2017).
DAA treatment uptake An estimated 58,280 individuals initiated DAA treatment through the PBS between March 2016 and March 2018 in Australia, including 20,600
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 March 2016 and March 2018, by jurisdiction 26%
27%
24%
32%
22%
34%
33%
17%
Estimated number of individuals initiating treatment
22000 20000 18000 16000
NSW: New South Wales; VIC: Victoria; QLD: Queensland; SA: South Australia; WA: Western Australia; ATC: Australian Capital Territory; TAS: Tasmania; NT: Northern Territory
14000 12000 10000 8000 6000 4000 2000 0
NSW
VIC
QLD
SA
WA
ACT
TAS
NT
2. For an estimated 10 individuals, more than one jurisdiction were recorded. 3. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052
Issue #9
2
0
Issue #9 Figure 2C
300
250
100
50 Mar 18
150
Mar 18
200 Feb 18
SA WA ACT TAS NT
Feb 18
1600
Jan 18
Dec 17
Nov 17
Oct 17
Sep 17
Aug 17
Jul 17
Jun 17
May 17
Apr 17
Mar 17
Feb 17
Figure 2B
Jan 18
Dec 17
Nov 17
Oct 17
Sep 17
Aug 17
Jul 17
Jun 17
May 17
Apr 17
Mar 17
350
Feb 17
1800
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
Mar 18
Feb 18
Jan 18
Dec 17
Nov 17
Oct 17
Sep 17
Aug 17
Jul 17
Jun 17
May 17
Apr 17
Mar 17
Feb 17
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
Mar 16
Estimated number of individuals initiating treatment 5500
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
0 Mar 16
Estimated number of individuals initiating treatment
0
Mar 16
Estimated number of individuals initiating treatment
Figure 2: Estimated number of individuals initiating DAA treatment in each month during March 2016 to March 2018 in Australia (A), and by Jurisdiction (B and C) Figure 2A
5000
4500
4000
3500
3000
2500
2000
1500
1000
500
NSW VIC QLD
1400
1200
1000
800
600
400
200
NSW: New South Wales; VIC: Victoria; QLD: Queensland; SA: South Australia; WA: Western Australia; ATC: Australian Capital Territory; TAS: Tasmania; NT: Northern Territory
3
Gender and age distribution of individuals initiating DAA treatment Of individuals initiating DAA treatment between March 2016 and March 2018, 67% were men and 33% were women. Age distribution of individuals initiating DAA treatment was similar between men and women (Figure 3). The highest proportion of total individuals were 51-60 years old (35%), followed by 41-50 years old (25%). Compared to the age distribution of the total population living with chronic HCV infection in Australia, a shift towards older age groups was observed among those initiating DAA treatment (Figure 3). The age distribution of individuals initiating DAA treatment in each month is illustrated in Figure 4. A trend towards younger age groups is observed from March to December 2016, with 28% in March compared to 61% in December being ≤50 years old. A relatively constant pattern in age distribution has been observed since January 2017. During the first three months of 2018 (January to March), 62% of individuals initiating DAA treatment were ≤50 years old.
Figure 3: Age distribution of individuals living with chronic HCV infection in 20154 (dotted line) and those initiating DAA treatment during March 2016 to March 2018 (bars)
40% 35% 30% 25% 20% 15% 10% 5% 0%
<21
21-30 31-40 41-50 51-60 61-70
>70
Age group
Men
Women
Estimated age distribution of people living with chronic HCV infection in Australia
4. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052
Issue #9
4
0%
Issue #9 Sep 17 Oct 17 Nov 17 Dec 17 Jan 18 Feb 18 Mar 18
Sep 17 Oct 17 Nov 17 Dec 17 Jan 18 Feb 18 Mar 18
Feb 17
Aug 17
10%
Aug 17
20% Jul 17
30%
Jul 17
40% Jun 17
50%
Jun 17
60% May 17
70%
May 17
80% Apr 17
90%
Apr 17
100% Mar 17
Figure 4B
Mar 17
Feb 17
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
5500
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
Mar 16
0
Mar 16
Estimated number of individuals initiating treatment
Figure 4: Absolute frequency (A) and relative frequency (B) of age groups of individuals initiating DAA treatment in each month during March 2016 to March 2018 Figure 4A
5000 ≤30
4500 31-40
4000 41-50
3500
3000 51-60
2500 ≥61
2000
1500
1000
500
5
Distribution of regimens prescribed for individuals initiating DAA treatment Overall, the most commonly prescribed regimen was sofosbuvir/ledipasvir±ribavirin for 45%, followed by sofosbuvir+daclatasvir±ribavirin for 32%, and sofosbuvir/velpatasvir for 14%. Since August 2017, when sofosbuvir/velpatasvir was PBS listed, this regimen has been the most commonly prescribed regimen, with 64% of 13,090 individuals initiating DAA since August 2017 prescribed sofosbuvir/velpatasvir (Figure 5). This regimen has been the most commonly prescribed regimen in every month since August 2018 (Figure 6). Availability of sofosbuvir/velpatasvir has had a limited impact on prescribing of elbasvir/ grazoprevir given this regimen was prescribed for 13% of individuals during January-July 2017 compared to 10% during August 2017-March 2018 (Figure 5).
The breakdown of treatment initiation numbers by treatment regimen and treatment course duration is shown in Figure 7. Of individuals initiated on sofosbuvir/ledipasvir±ribavirin (n=25,970), 17% were prescribed an 8-week course, 74% a 12-week course, and 9% a 24-week course. Of individuals initiated on sofosbuvir+daclatasvir±ribavirin (n=18,470), 69% were prescribed a 12-week course, and 31% a 24-week course. Of individuals initiated on elbasvir/ grazoprevir±ribavirin (n=3,020), 97% were prescribed a 12-week course, and 3% a 16-week course. Of individuals initiated on paritaprevir/ritonavir/ ombitasvir+dasabuvir±ribavirin (n=790), 86% were prescribed a 12-week course, and 14% a 24-week course.
Figure 5: Distribution of DAA regimens prescribed during March 2016 to March 2018 (overall), January to July 2017 (seven months prior to SOF/VEL being PBS listed), and August 2017 to March 2018 (seven months from SOF/VEL being PBS listed) 100%
SOF/VEL
90%
EBR/GZR±RBV
80%
PrOD±RBV
70% 60%
SOF+Others
50%
SOF+DCV±RBV
40%
SOF/LDV±RBV
30% 20% 10% 0%
March 2016 to March 2018
January to July 2017
August 2017 to March 2018
SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; GZR: Grazoprevir; PrOD: Paritaprevir/ritonavir/Ombitasvir+Dasabuvir; VEL: Velpatasvir; RBV: Ribavirin
Issue #9
6
0%
Issue #9 Sep 17 Oct 17 Nov 17 Dec 17 Jan 18 Feb 18 Mar 18
Sep 17 Oct 17 Nov 17 Dec 17 Jan 18 Feb 18 Mar 18
Feb 17
Aug 17
10%
Aug 17
20% Jul 17
30%
Jul 17
40% Jun 17
50%
Jun 17
60% May 17
70%
May 17
80% Apr 17
90%
Apr 17
100% Mar 17
Figure 6B
Mar 17
Feb 17
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
5500
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
Mar 16
0
Mar 16
Estimated number of individuals initiating treatment
Figure 6: Absolute frequency (A) and relative frequency (B) of DAA regimens prescribed for individuals initiating DAA treatment in each month during March 2016 to March 2018 Figure 6A SOF/VEL
5000 EBR/GZR±RBV
4500 PrOD±RBV
4000 SOF+Others
3500 SOF+DCV±RBV
3000
2500 SOF/LDV±RBV
2000
1500
1000
500
7
Distribution of health care providers prescribing for individuals initiating DAA treatment
Figure 7: Distribution of DAA regimens prescribed during March 2016 to March 2018, by treatment regimen and treatment course duration (16 weeks treatment exclusively applies to EBR/GZR+RBV)
Most individuals initiating DAA treatment received their prescriptions from gastroenterologists (42%), followed by general practitioners (GPs; 27%), infectious diseases physicians (7%), and other specialists (3%). Twenty-one percent of individuals received their prescriptions from other physicians (Figure 8). Overall, 52% of individuals received their prescriptions from specialists.
Estimated number of patients initiating treatment
26000
Distribution of prescriber types varied across jurisdictions (Figure 8). Gastroenterologists were the prominent prescriber in most jurisdictions. In Northern Territory, 24% of individuals were prescribed DAA treatment by GPs and 21% by infectious disease physicians, compared to 4% by gastroenterologists. In Western Australia, 30% of individuals were prescribed DAA treatment by GPs, compared to 17% by gastroenterologists. Across jurisdictions, the proportion of individuals prescribed DAA treatment by GPs was highest in Tasmania (36%), Queensland (32%), and Western Australia (30%).
16/24 weeks
24000
12 weeks
22000 20000
8 weeks
18000 16000 14000 12000 10000 8000 6000 4000 2000 0
SOF/ LDV± RBV
SOF+ DCV± RBV
SOF/ VEL
EBR/ GZR± RBV
PrOD± RBV
SOF: Sofosbuvir; LDV: Ledipasvir; DCV: Daclatasvir; EBR: Elbasvir; GZR: Grazoprevir; PrOD: Paritaprevir/ritonavir/Ombitasvir+Dasabuvir; VEL: Velpatasvir; RBV: Ribavirin
Figure 8: Distribution of prescriber types for individuals initiating DAA treatment during March 2016 to March 2018, in Australia and by jurisdiction 100%
Other physicians
90%
General Practitioners
80% 70%
Other Specialists
60% 50%
Infectious Diseases 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, other/unclassified non-specialist and undefined.
Issue #9
8
Distribution of prescribed DAA regimens by prescription type
The distribution of prescriber types in each month is shown in Figure 9. The proportion of individuals prescribed DAA treatment by GPs increased from 8% in March 2016 to 40% in May 2017, followed by a relatively constant trend since then. During the first three months of 2018 (January to March), 38% of individuals initiating DAA treatment were prescribed treatment by GPs (Figure 9B). Increasing contribution of GPs in DAA prescribing is also evident by increasing the absolute number of individuals initiated on DAA treatment by GPs, from 410 in March 2016 to 790 in October 2017. Since November 2017, an average of 540 individuals per month were initiated on DAA treatment by GPs (Figure 9A).
The distribution of prescribed DAA regimens by prescriber type is shown in Figure 10. Across all prescriber types, the most commonly prescribed regimens included 12 weeks sofosbuvir/ledipasvir, followed by 12 weeks sofosbuvir+daclatasvir (Figure 10A). Of prescriptions by specialists, an overall 18% included an extended duration regimen (24 weeks sofosbuvir/ledipasvir or sofosbuvir+daclatasvir and 16 weeks elbasvir/grazoprevir) compared to 6% of prescriptions by GPs (Figure 10A). Of the total number of prescriptions of extended duration regimen,
Figure 9: Absolute frequency (A) and relative frequency (B) of prescriber types in each month for individuals initiating DAA treatment during March 2016 to March 2018 in Australia 5500
Other physicians
Figure 9A
5000
General Practitioners
4500
Other Specialists
4000 3500
Infectious Diseases Physicians
3000
Gastroenterologists
2500 2000 1500 1000
May 17
Jun 17
Jul 17
Aug 17
Sep 17
Oct 17
Nov 17
Dec 17
Jan 18
Feb 18
Mar 18
May 17
Jun 17
Jul 17
Aug 17
Sep 17
Oct 17
Nov 17
Dec 17
Jan 18
Feb 18
Mar 18
Apr 17
Mar 17
Feb 17
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
0
Mar 16
500
Figure 9B 100% 90% 80% 70% 60% 50% 40% 30% 20%
Apr 17
Mar 17
Feb 17
Jan 17
Dec 16
Nov 16
Oct 16
Sep 16
Aug 16
Jul 16
Jun 16
May 16
Apr 16
0%
Mar 16
10%
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.
Issue #9
9
69% was by specialists compared to 11% by GPs (Figure 10B). These regimens are primarily prescribed for patients with cirrhosis.5
This regimen is prescribed for treatment-naĂŻve patients with genotype 1, no cirrhosis, and pre-treatment HCV RNA<6 million IU/mL.5
Across all prescriber types, the highest proportion of 8 weeks sofosbuvir/ledipasvir regimen was observed in prescriptions by GPs (10%, Figure 10A). Of the total number of 8 weeks sofosbuvir/ledipasvir prescriptions, the majority was by GPs (35%, Figure 10B).
Of the total number of sofosbuvir/velpatasvir prescriptions, the proportions by specialists and GPs were comparable with 40% prescribed by specialist (30% by Gastroenterologists), and 30% by GPs (Figure 10B).
Figure 10: 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 March 2018 in Australia Figure 10A 100%
Other regimens
90%
EBR/GZR 12 wk
80%
EBR/GZR 16 wk
70%
SOF/VEL 12 wk
60%
SOF+DCV 24 wk
50% 40%
SOF+DCV 12 wk
30%
SOF/LDV 24 wk
20%
SOF/LDV 12 wk
10%
SOF/LDV 8 wk
0%
Gastroenterologists
Infectious Diseases Physicians
Other Specialists
General Practitioners
Other Physicians
Figure 10B 100%
Other physicians
90%
General Practitioners
80% 70%
Other Specialists
60% 50%
Infectious Diseases Physicians
40%
Gastroenterologists
30% 20% 10% 0%
SOF/LDV 8 wk
SOF/LDV 12 wk
SOF/LDV SOF+DCV SOF+DCV SOF/VEL 24 wk 12 wk 24 wk 12 wk
EBR/GZR EBR/GZR Other 16 wk 12 wk Regimens
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
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 #9
10
Methodology The methods for the estimations have been described in detail elsewhere.6 In brief, the following data sources were used for analysis: â&#x20AC;˘ The data of a longitudinal cohort of individuals, representing a 10% random sample of the PBS database were used to estimate the number of individuals initiating DAA between March 2016 and March 2018, and for all sub-group analyses of DAA treatment uptake. â&#x20AC;˘ The estimated numbers of individuals living with chronic HCV infection in Australia and in each jurisdiction in 2015, and age distribution among individuals living with chronic HCV infection were extracted from a modelling study.7
There are some factors that should be considered in interpreting the results. Given that the results are extrapolated from 10% random sample of the PBS database, the results in subgroups with small numbers might be subject to uncertainties. This analysis provided data of treatment initiations. It does not reflect the number of individuals who completed their treatment course, although treatment discontinuation is expected to be low. The jurisdiction-specific treatment initiation estimates in this report are based on data of dispensing pharmacy location, and not patientâ&#x20AC;&#x2122;s residence location while the estimated numbers of individuals living with chronic HCV are based in part on the number of HCV notifications which are reported based on residence. Thus 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.
6. 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. 7. The Kirby Institute. Hepatitis B and C in Australia Annual Surveillance Report Supplement 2016. The Kirby Institute, UNSW Sydney, Sydney NSW 2052
Issue #9
11