Top 10 drugs 2021-22 and 2022-23

We don't see broad-spectrum antibiotics appear in the top 10 of utilisation, doesn't mean that we don't have more that we could do, or that we don't have a potential looming problem. So I think it's far from the time to get complacent.

[Music] Welcome to the Australian Prescriber Podcast. An independent, no-nonsense podcast for busy health professionals.

I'm Dhineli Perera, your host for this episode, and it's a pleasure to be speaking to Dr David Liew today about Australia's top 10 drugs over the last 2 years. So that's 2021 to '22 and 2022 to '23. David's voice may sound familiar as he's usually sitting in my seat asking the questions for this podcast. However, he's also the project lead for the Medicines Optimisation Service at Austin Health, a clinical pharmacologist and rheumatologist, as well as a member for the Drug Utilisation Sub Committee of the Pharmaceutical Benefits Advisory Committee. So that's quite a few hats that you wear there, David. Could you tell us a bit about the Drug Utilisation Sub Committee? I guess it's quite a pertinent position given the topic of discussion today.

Absolutely, and it's really fascinating to see the interest that Australian Prescriber's had over the nearly 30 years that they've been publishing the top 10 drugs. I guess you think about all the other articles that Australian Prescriber provides and the vast majority of them are directly clinically applicable. They help to guide everyday practice. This is something which is a little bit different, but people are still very curious. How this works as a whole is of interest to us as clinicians and I think to the broader public. So I should say, first of all, of course everything I say today really just represents my personal opinions and not the opinions of the Drug Utilisation Sub Committee or of anything to do with the Australian Government.

Drug Utilisation Sub Committee is one of the 2 subcommittees of the PBAC. The PBAC, firstly, decides on which medicines should be on the PBS and also monitors how that utilisation is going over time, and makes adjustments depending on submissions that come in. So the PBAC makes those overall decisions, but it gets informed by 2 subcommittees. So the ESC, the Economic Sub Committee, which looks at the clinical claims that are made by submissions and looks at the pharmaco-economics, so sees whether the claims that are made and the submissions that are made based on the prices that are offered, really offer the Australian taxpayer bang for buck. And then the Drug Utilisation Sub Committee looks at things like quality use of medicine, but also looks at the pharmaco-epidemiological side of things. So really how medicines are utilised and what the financial implications are. So how much that leads to overall spend, not necessarily about cost-effectiveness, but about the overall utilisation.

So that's where this is really pertinent. Of course, everything that gets discussed in those committees, is in confidence and there's a lot of stuff that gets discussed behind closed doors to try and further the taxpayer benefit that we get from the PBS. Of course the medicines that we buy, the prices do get negotiated, so we know that the prices that get listed in this article, for example, aren't necessarily what the Australian taxpayer is paying. Often there are some special pricing agreements, so maybe we might be getting some discounts that the manufacturer's offering that aren't public knowledge. There might be risk-sharing agreements, that is to say when we use a certain amount as a country, then after that we get price reductions or maybe we get it for free.

There's all sorts of different pricing structures. But using publicly available knowledge, and we'll only talk about publicly available knowledge today, we could get an idea as to what the, at least, theoretical cost to the government is for all these medicines based on the utilisation and then the list price that we see published as part of the PBS. And we can see the utilisation for medicines by prescription, so per actual prescription given. And then we've also got data here from the defined daily dose (DDD), which is a WHO measure of roughly, per X number of population, how much medicine we're using of that particular medicine standardised for the kind of average daily dose that you'd have.

Thank you for explaining those 3 tables. I think it's something that's definitely worth knowing or at least for the reader to know what the difference is between them all. So coming back to Tables 1 [DDD] and 2 [prescription counts], David, for the last 2 and even 3 years, there are some obvious similarities. The statins, atorvastatin and rosuvastatin, continue to be at the top there. Do you think there will be a time when we will see this pattern change? Will we see the statins ever leave or do you think they're here for good?

It's really interesting, isn't it? Because first of all to say that they used to feature in Table 3 [cost to government], if you go back over 20 years, simvastatin, atorvastatin were top of the cost to government. And one of the main reasons why medicines drop further down that cost to government table, is that you either have generics or biosimilars depending on whether you're looking at small molecules or monoclonal antibodies, large molecules. And because of that, the cost drops down through competition and then you see the cost to government, at least that theoretical cost to government, drop down. And so we've seen that, but we still see rosuvastatin, atorvastatin at the top of both Tables 1 and 2. So both by defined daily dose as well as by prescription counts. And I guess that's not surprising; cardiovascular disease, it's common. Even as we see cardiovascular-related deaths drop, we still see that dyslipidaemia is common, dyslipidaemia is still getting more common, the overall burden of cardiovascular disease is quite large.

And so it's really not surprising to see those statins there. And we hope that means that this statin use is part of what's driving reductions in cardiovascular-related death. Will these disappear from the top of the tables anytime soon? Well, it always takes a certain kind of fool to make predictions on a podcast like this, but I think that it's fair to say that the cardiovascular burden is not going anywhere. We've still got an ageing population, and these are the kind of medicines that you do tend to take when you do get a little bit older., And so I think for the time being they're still going to be there or thereabouts at the top and it's hard to see other medicines really surpassing them at the moment. Looking at those top 10 for defined daily dose and by prescription count, nothing really screams out as something where practice is going to change so dramatically that it's going to overtake. I mean, the gap is quite large, so rosuvastatin, 16 million prescriptions in '22–23, compared to, going down to number 10, amlodipine down at 4.9 million. So there's a really big gap. We'll do this again in 5 years and it'll still be there at the top.

I think so too. I also said last time that I was relieved as an AMS pharmacist to see no broad-spectrum antibiotics have made their way to the top 10 list. And this is different to what was noted in the same tables from a few decades ago. In your opinion, do you think it's overly optimistic to suggest that this is due to an increased awareness about antibiotic resistance?

Oh, I'm sure it is. If you compare how we were thinking in the '90s to how we're thinking now, clearly our attitudes have changed and that speaks to the success of antimicrobial stewardship, not only as a broad concept, but in terms of how it's been executed in Australia.

We've been good at that and I think we should be pleased with the progress we've made. Now of course, just because we don't see broad-spectrum antibiotics appear in the top 10 of utilisation, doesn't mean that there's not potentially inappropriate use going on, or that they're not being used widely, or that we don't have more that we could do, or that we don't have a potential looming problem still. So I think it's far from the time to get complacent.

And I guess just to finish off on that, there's also the thought that now that most of those broader-spectrum antibiotics, something similar to ciprofloxacin for example, is available as a generic, there is the option that they are being prescribed off the PBS as well. So this is really reflecting just the PBS prescribing of it, but not necessarily all prescribing in the community.

Absolutely.

Something to keep in mind.

Now moving on to the harder-to-pronounce drugs. So aflibercept, a drug for macular degeneration, has held the undesirable spot of most expensive drug to the government for many years. In the '22–23 list, however, this moved down to third position and molnupiravir, the COVID-19 antiviral therapy, was the most expensive drug for last year. Would you like to comment on this outcome, David?

I mean, it's fascinating, isn't it? And I guess it's easy to forget the kind of remarkable times that we've come from not so long ago, right? And listeners might remember that we did have a medicine stockpile, we do have a medicine stockpile, and that we were scrambling around to find antivirals not so long ago. It was a precious commodity that we weren't able to readily access, that we had to compete for globally, very aggressively. We had to get our hands on what we could and without being able to really precisely predict exactly how much we might need. So really aflibercept’s been there or thereabouts, but molnupiravir, and nirmatrelvir [and] ritonavir (Paxlovid), they're on the top 10 list. I think it's a little bit of an artefact because we've bought a whole lot of medicine, it's sitting in a stockpile, and it’s on the public record that we are making decisions on the basis that we've got a whole heap there and that at some point that's going to expire as well. We need to try and get through it. It doesn't last forever.

So the decisions that we've been making have been on that basis, but there's been a lot of thought about what we do going forward. Clearly the impact of COVID-19 is changing. The impact of antivirals on prevalent variants of COVID-19 in the community is changing as well. And so it means that we have to make some interesting decisions. Now, the other question is why is molnupiravir at the top of the list when it's meant to be second line after nirmatrelvir [and] ritonavir (after Paxlovid)?

I think it probably speaks a little bit to the concerns that prescribers have when they think about nirmatrelvir [and] ritonavir, and they think potentially about drug–drug interactions. Even though we've got interaction checkers readily available, it can be the kind of thing that seems a little bit intimidating even though we know that nirmatrelvir [and] ritonavir is more impactful than molnupiravir, and should be first line. And we know as well, that those drug–drug interactions, even if we look at COVID-administered medicines, potentially the impact of that might not be as much as some might worry. So I would like to think that we could do better on that and make sure that we prescribe the most impactful COVID-19 antivirals that we can for any given individual patient. That we wouldn't be discouraged by the potential for interactions and that we would use the interaction checkers as we should.

And just to add to that, in terms of a practical component for that, if there are prescribers or clinicians that aren't aware about those freely available interaction checkers, the Liverpool Interaction Checker is the one that we utilise or I utilise in my practice, and it's actually quite user-friendly and easy to use.

The cystic fibrosis drug though, David, that I cannot even pronounce, so I'm going to try it— elexacaftor+tezacaftor+ivacaftor, also known as Trikafta—made its way onto the PBS in 2021 and is now the second most expensive drug to the government. It has a noticeably smaller volume than the other drugs on the list, meaning obviously that it's a very high-cost drug. And I wondered whether you thought that this pattern of high cost, low volume will continue to dominate the PBS expenditure for years to come?

I'd say that it's not necessarily dominating now, although, obviously, it's presence is very palpable. And I guess that, when it comes to something like Trikafta, then it's something that's been highly scrutinised. At the same time it's gone through a process where we've seen the cost-effectiveness, and we've gone about this in a way that we hope is delivering benefit to Australians as far as the impact of medicines are concerned. So, yes, I think it's notable. And when you think about 24,000 prescriptions, which is what it was in '22–23, and you talk about a theoretical cost of half a billion dollars, then yes, I think that's something that we are alert to. Of course, if you look at those top 10 in terms of spend, there are other low-volume medicines there, and there is this potential pattern of high-cost, low-volume medicines for highly specialised outcomes that really are delivering enormous impact in the patients who are eligible for these.

But we've got to be very careful about who we use these medicines for, and that's part of the reason why all of this scrutiny is so important. To make sure that we are getting the medicine that's required to the patients who need it, but not giving it to patients where the benefit is less, because we as Australian taxpayers really should demand that we are getting the value for money in terms of the benefit we see for the patients that we treat.

Absolutely, and I think these niche indications are often the ones that are harder for the pipeline of drugs to come through. So the fact that it has come through is only a good thing if it's giving patients with cystic fibrosis a chance at something that they didn't have before.

But I guess a bit less surprising is the fact that 5 out of the 10 most expensive PBS drugs are monoclonal antibodies [mAbs]. Has this been a gradual shift? I guess you are probably a prescriber of this yourself, and do you expect that the mAbs will continue to be present on this list for years to come, or do you expect that the cost will really reduce?

I think that it already has to an extent. Some of the monoclonal antibodies there, nivolumab, pembrolizumab, are used within the cancer space. These are checkpoint inhibitors, so they're inhibiting PD-1 and they're being used with great impact in a broad range of cancers and ever-broadening. What we've seen, however, is that adalimumab, which used to be, if you go back 10 years, was top of the list But we've seen it drop right down to 9 and we'll probably see it drop off the list at some point because of the fact that it's come off patent and now we've got a vibrant biosimilar environment where there's competition, and competition fundamentally drives down price. We've seen etanercept used to be on the top 10, now no longer on there. We've seen rituximab used to be on the top 10, now no longer on there. Those are both highly impactful medicines, both still being used broadly, and both leading to a lot of benefit for a lot of patients, but we've seen them fall off that list. So I think that speaks to the potential benefit that we can see from biosimilars.

Absolutely. And then looking at apixaban on there as well, if you think about how life-changing that is for patients that really only had warfarin as an option not long ago for oral anticoagulation, the fact that it's now so frequently prescribed and, yes, it is a high-cost item on our expense list, but there are so many other expenses now that are being avoided by using that, like transportation to get to centres, to get blood tests, to get the results, to send out results and dose people. All of that is now being avoided with the NOACs [non-vitamin K antagonist oral anticoagulants]. It is a very multifaceted reason as to why some of these costs are probably not really representative of the full cost-saving to the government as well.

Well, to us as Australian taxpayers, right?

Yes.

I mean, this is our money, right?

100%.

And of course, this doesn't even fully reflect the benefit that we might see in terms of the prices that we're really negotiating behind the scenes.

Finally, David, could you tell us some changes that you predict you'll see in the lists for the next year or two?

Yes. Well, I think that it's entirely possible that we'll see other checkpoint inhibitors enter the top 10 cost list. Once again, with all the provisos I made before, but we are seeing more and more indications come online for PD-1 inhibitors, PD-L1 inhibitors. It wouldn't be surprising to see them continue to feature on the top 10 list of costs. I think there's some difficult decisions that are being made about where we sit with COVID-19 antivirals. I think that's what the Australian public would expect, and I really look forward to seeing how that plays out and hoping that we, as Australian taxpayers, get best bang for buck and make sure that we can protect the patients that we need to from the severe complications of COVID-19, but at the same time, make sure that we do so in a way which is going to deliver the best benefit for the health system.

And I think that it's entirely possible as well, that we won't see much change in the top 10 in terms of utilisation by defined daily dose and by prescription counts. Because really, medicines that are on there, really treating the metabolic syndrome more broadly, that's what's dominating both of those lists. The metabolic syndrome isn't going anywhere.

Final thing I'd say, of course, is that it's entirely possible that there are medicines that aren't listed on the PBS right now, which may well jump onto there.

Excellent. Well, thank you so much, David. That's unfortunately all the time we've got for this episode. It's been a pleasure chatting to you today.

It's been a pleasure chatting to you, Dhineli. Always happy to talk about medicines.

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The top 10 drugs article is available on the Australian Prescriber website. The views of the hosts and guests on the podcasts are their own and may not represent Australian Prescriber or therapeutic guidelines. Dr David Liew is a member of the Drug Utilisation Sub Committee of the Pharmaceutical Benefits Advisory Committee. I'm Dhineli Perera, and thanks for joining us on the Australian Prescriber Podcast.