RheumNow Podcast - I Wanna New Drug (8 - 30 - 19) Save

This is the Room Now podcast for 08/30/2019. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. This week, something a little different. A slow news week.

I thought I'd talk to you about drugs. Specifically, the answer to the question, what drug am I going to use? What's my favorite drug? I can't answer this question. Rheumatologists usually clam up because we say there's no one right answer to the question, especially when it's being posed by someone who's selling a drug.

And even as difficult when it's being asked by a patient. We say it's because of many factors, including that all patients are different. But this is a common issue. We're pressed for the answer. It's common because the marketplace has gotten real busy.

There's new JAK inhibitors, there's IL-seventeen inhibitors, there's new cytokine targeted therapies. And again, they're all vying for a position on my dance card. I don't know who's really going to get there or who belongs there. We often will respond back, Well, is this drug better? Is this drug safer?

And is this drugs cheaper? Well, the answer to all those questions when it comes to new therapies is generally no, no, no. I'll give you an asterisk for the cheaper one. All JAK inhibitors and biologics are about the same in The US at $60,000 a patient. Well, baricitinib was priced at about half that price, around $25,000 Again, it doesn't matter to the patient who has an insurance policy and a copay card and their out of pocket costs are about the same.

I don't know if money drives this equation as much as we rheumatologists would like to talk about. But, you know, this used to be an also difficult question, but maybe a little clearer in the pre biologic, even pre methotrexate era, when we had a lot of drugs to treat RA. And we needed all of them because the drugs, A, weren't as effective, B, didn't have very good durability largely because of toxicity, and then secondly, because of a loss of efficacy. And I used to say I needed nine drugs or a baseball team to treat someone with rheumatoid arthritis because I was going to cycle through my first three in the first two years. And then what am I going to do for the next fifteen or twenty years?

Then in 'eighty four, methotrexate came along and changed the game. It was going to be the go to choice because it outperformed all the other choices and because it had great durability with, you know, at 50, at five years later, seventy percent of patients were still on the drug. To this day, not many drugs have the same durability as does methotrexate. The rest of them basically were standing in line to be dance partners with methotrexate in some sort of combination therapy. And that was the combination therapy era from 'eighty four to roughly 2000.

We still believe in combination therapy because of the experience and the data gained during that era. But then of course, it all changed with these new biologic therapies. And these came along 1998 and flourished in the early 2000s. What happened to the old drugs? You know, sulfasalazine and gold and penicillamine, they've really fallen to the back of the list.

Only sulfasalazine seems to get some use. Arava gets some use. Hydroxychloroquine is a safe drug that doesn't do much for anybody unless you combine it with someone. But the biologics in combination therapy and methotrexate have been really the paradigm shift since the 2000s. The problem is that advances in immunology hasn't necessarily been an advance in therapy because of the cost of therapies and because these agents actually aren't much better than what we were doing and they aren't much safer.

And that's really one of their downsides. Plus, they're more expensive. They certainly work faster. They certainly may be easier to give. Their toxicity profile, they have less nuisance toxicity and their rare toxicities are rare, just like they are with azathioprine or penicillin or whatever.

So it becomes more and more difficult as we have these new therapies, mainly because of the numbers. I have over 30 drugs that I can use to treat rheumatoid arthritis, 19 biologics alone, and I'm having a hard time telling the difference between any of them, especially when a bunch of them, eight or nine of them, eight of them, I think, are biosimilars who are designed to be exactly the same as the innovator biologic for which they're copied after. So, the problem is that these 30 plus drugs and 19 plus biologics are all vying for that same position in my therapeutic arsenal. The deal is that I don't need nine drugs to treat RA anymore. We've gotten better at treating RA.

I might need three to get an RA patient through the first five or ten years of their disease. So they're to be three of my top favorites. They're going to be three that are mandated by managed care. It's not an easy decision, although we try to make it easy. It gets uneasy when we're asked to change.

So who's asking us to change? Well, proponents are treat to target, suggest that maybe you should change more. And it's good data to say that you don't change enough as a rheumatologist and that you let patients fly in the face of moderate to severe disease activity despite, the number of drugs that you have at your disposal. Who else says we should change? Well, obviously people selling the drug, should say we should change.

And then managed care, when we do want to change, they tell us, Oh, no, your change is all wrong. Our change is better because it makes us more money. So change is good, I think, for almost anything in life. It's scary, but it's good. It's hard to sell to patients who don't want to change, patients who may not be in remission, but may be in low disease or God forbid, moderate disease activity.

They're afraid of the drug that they don't know, the drug that you are maybe sure is going to help them. And you know, life gets even more difficult because change involves dealing with insurers and pharmacy benefit managers and prescribing rules and formulary exemptions and prior authorizations, which is a medical version of The Hunger Games and Dumber and Dumber. Put those two movies together and that's my prior authorization operation in my clinic. A thing that I fund totally so that I can sell someone else's drug. I don't get it.

That shouldn't happen. So, need three drugs. And the question is, which three? I think that most of us would say it's out of my hands. They tell me what the three are, especially if I'm starting out in biologic therapy.

The question is beyond the first one or two, you know, guidelines have leveled the playing field so that many drugs can now be used maybe first line, but certainly second line because guidelines are based on evidence. Evidence is based on well done trials. The only people doing well done trials are the drug companies making the new drugs. There is no evidence based therapy as to when you should use the combination of methotrexate and azathioprine or Arava and Gold together. I mean, theoretically, they probably would work very well, but no one's doing that study, so they're not on any formulary.

So the companies are pushing hard and it's their job. And, you know, you as prescribers point to them as affording you all the new materials you need to be better at your job. The question is, who's going to change? They want to know, the manufacturers, which one of you is an easy rider? Meaning someone, not writer, it could be writer, it could be writer, with the motorcycles.

A la Peter Fonda, rest in peace. But they really mean early adopters, those who are amenable to change, those who, you know, new drug, cool, let's try it. That's a minority of you. The rest is split between, you know, switchers, people who may be malleable about changing from one drug to another, and then the true believers who swear by their drug or their two drugs. And how people get into these categories is unknown.

It's a lot based on your personality or exposure, whether you did research. Marketing plays a role. Switchers are probably pretty hard to change because many of them have one foot in the true believing thing, the other foot in uncertainty. And that's a difficult combination to deal with if you're trying to change the way they think. True believers are convinced in the story that's inside their head about etanercept is the only drug that works in rheumatoid arthritis and is clearly better than everything, every other TNF inhibitors, although there's no data to support that at all.

So this is what we're all up against if we're looking at change. So what's it going to take for you to change your prescribing habits? I think that, you know, change is hard, as we said. The problem is front end change. Changing my top three drugs that I'm going to use is really difficult because we all get sixtyfortytwenty responses.

In these new drugs when they're given to methotrexate incomplete non responders or incomplete responders. And until someone breaks the ceiling as they did in psoriasis, they went from PASI 75 scores, now the best drugs are talking PASI 100. They found drugs that actually broke through the ceiling. Then you'll see the front end changes. Until then, everybody is really vying for a position based on either emotion or based on data, what, that they're better, safer, cheaper.

Again, that doesn't really exist. So vying for the next slots after my top three, I think is really predicated on defensive prescribing, understanding the situation that that patient is in. Do they have interstitial lung disease? Have they had GI problems with pasties? Do they have a past chronic perforation?

Do they have a history of a deep vein thrombosis? Do they have a history of recurrent infections and you end up slow or history of hepatitis? I mean, can go on and on, fear of cancer. And the idea is patients end up sort of deselecting the drugs that they can't take and leaving behind the options that are left for you, the prescriber. And I don't know if this is the best way to manage a patient.

I don't think it is. But this is the reality that we are dealing with. So if you're a doc, you need to look critically at your own prescribing habits and what are your policies on developing a new one? My friend Danny Ricciardi, a Brooklyn rheumatologist, says, I got too many drugs to treat psoriatic arthritis. I don't know when I'm going get around to the last one that was in my office telling me how great it is.

And that's true. You know, patients are doing great with many old therapies, many new therapies. And, you know, I don't think you should be changing drugs because it's the newly advertised drug or because of some new claim. You change drugs when the last drug didn't work and the patient has active disease or when they can't tolerate If you're a company with these grandiose expectations as to what I might do with your new drug, well, you're moving a mountain, a mountain of habits that are based in history. And it's not going to be easy.

It's not going to be cheap. You need to come with the ability to either reshape or reposition your drug. You need to come with data showing multiple indications on your drug so as to sort of develop a confidence in that drug that I might be willing to now give it in the primary indication or a secondary indication. And if not that, you better come with data that shows that you are the precision medicine of the future. All these drugs are the same until someone shows me the test, the profile of a patient that says this new drug, this new BTK inhibitor is going to work better than a TNF inhibitor, or better than a JAK inhibitor, better than an IL-six inhibitor because of this profile.

It gives you an added advantage and you're not going to get 64, eighty twenty, you're going to get 85, 65, 55. Then it's hard to argue with that kind of data. Until then, it's still a coin flip. So when you want a new drug, good luck.