Lawrence Green, MD, Offers His Take on Selecting Biologics

Lawrence Green, MD, section editor of the Psoriasis Centers of Excellence, associate clinical professor of dermatology at George Washington University School of Medicine in Washington, DC, and on the National Psoriasis Foundation Medical Board, reviews current biologic therapies available for psoriasis and shares his methods for selecting the appropriate biologic for patients.

Transcript

Hello, my name is Larry Green, or Lawrence J Green. I’m Associate Clinical Professor of Dermatology, George Washington University School of Medicine in Washington, DC. Today, we’re going to talk about assessing patients and determining factors for selecting an appropriate biologic.

There are many biologics, that’s for sure, and they are all very different, and so are our patients. The last thing we should think is that, if one biologic is not considered appropriate by an insurer or a pharmacy benefit manager that we can switch to another because it’s all the same. Biologics are not the same.

They do have various safety and efficacy profiles, and our patients need different things. It’s very important, and especially when it comes to talking to insurance companies, to select for a biologic that fits what the patient needs most.

That’s what we’re going to talk about in the next few minutes is how do you select a biologic that you think will fit what the patient needs most. And, I won’t be able to give you all those answers right now because everyone is unique. There’s not a group of patients that necessarily all fit one biologic.

We can generalize, that’s the best I can give you now, but every patient is unique and you have to take what I’m saying today and select from that and pick and choose what fits your patient’s needs best because they’re all unique.

Let’s start with categories of biologics. There are TNF biologics, there are IL-12/23 biologics, which there’s only one right now, and there’s IL-23 biologics, and IL-17 biologics. Those are the main types of biologics that are currently available on the market today.

Let’s talk by categories. We’ll start where I think each category would be appropriate for a patient. Let’s start with the anti-TNF therapies.

In dermatology, we have etanercept, which is 25-plus years old at this point. It’s been around a long time. We have adalimumab, which has been around almost as long.

Then we have other ones like infliximab, which is an infusion which is used less and less in dermatology so I’m not going to really go there. We have a newer TNF biologic called certolizumab, which has just been recently introduced.

These are all anti-TNFs and they are biologics we used to only have to treat psoriasis, but now it’s an older generation, especially when you go back 25 years with etanercept. These are good starter biologics, the anti-TNFs, and especially valuable for patients with more severe joint disease. That’s the way I look at the anti-TNFs at this point.

Remember, these are broader-spectrum agents. They’re more susceptible for patients to get tuberculosis than the other severe infections. These are things we do more laboratory monitoring with than we do with other biologics. But they’re good broad-spectrum therapy for someone with more broad-spectrum psoriasis, more severe joint disease, as well as skin disease.

That's the way I look at it. If it’s a new patient, I would use anti-TNF therapy. Now, etanercept is thought of, because there’s no intense head-to-head studies, but is thought of as being not as strong as adalimumab.

Certolizumab is a newer anti-TNF that is the only biologic that has an indication to be used in a woman who’s pregnant. Women with severe psoriasis, forget about joint disease, just severe psoriasis in general, if you want to go on-label, that’s the only biologic that can be used for someone who’s trying to conceive or is actively pregnant.

That’s a good way to look at certolizumab. But, again, I look at anti-TNFs as biologics for people with more severe joint disease, in general, except for certolizumab that's got that pregnancy indication. It doesn’t cross the placenta. What about the other ones?

Then we have an IL-12/23 inhibitor, ustekinumab, which has been available for a long time. It was our first non-TNF biologic.

This is definitely less risk for tuberculosis than the anti-TNFs, but it has a component, anti-IL-12, which really is unnecessary. Doesn’t help psoriasis at all, studies have shown. There’s no benefit in adding the anti-IL-12 profile to treat psoriasis.

I think this product is useful for really those people who are needle phobic because it can be given in the office. It can be given at home too, but it could also be given in the office because it's only four times a year.

I don’t recommend ustekinumab for someone who’s very heavy. Even though it’s weight-based, I’ve noticed in my own anecdotal experience, heavier the person is, even at the higher dose, it’s less effective.

But for someone with a modest, severe, mild psoriasis, not really covered, who really is needle phobic, I think ustekinumab is a great choice to start with. That’s how I look at that one.

Then we have the IL-17 biologics. These are fairly new in the last few years. We have three of them currently, more to come, near future. The three to come are secukinumab, ixekizumab, as well as brodalumab. Brodalumab is different than the other two, so let me start with ixekizumab and secukinumab.

Those are two similar anti-IL-17 biologics. I like the anti-IL-17s family for someone with very severe psoriasis, who really wants a quick onset of action, and also has joint disease. You don’t have to have joint disease.

In fact, the majority of my patients who are using anti-IL-17 don’t have joint disease, but it’s a very big added plus because these products work very well for joint disease.

I can’t compare them to anti-TNFs. The anti-TNFs are classic joint disease medications, still remain, but these are good broad-spectrum agents. You don’t have to worry about tuberculosis like the anti-TNFs. They do have a small risk for incurring Candida infections, either vaginally or orally. They’re not to be used in patients with inflammatory bowel disease.

Those are the caveats with the IL-17s. But they’re very effective. Someone has a lot of psoriasis, needs a quick onset of action product, the anti-IL-17s are an excellent choice.

Secukinumab and ixekizumab are anti-IL-17A antibody products so they stop production of IL-17A, which of course is elevated in psoriasis.

Brodalumab is another anti-IL-17. It’s more broader-spectrum anti-IL-17. It does more things than ixekizumab and secukinumab.

It is not approved for arthritis, although, theoretically, it should work and I’ve noticed anecdotally it does work for my patients with psoriatic arthritis as well. But, it’s broader-spectrum. It’s a very quick onset of action.

The downside though, it’s given every two weeks. The other anti-IL-17s are given once a month.

Now, these anti-IL-17s, like I said, have a quick onset of action. Very quick. Patients get improvement within a few weeks. That’s a plus, and I look at them for more severe psoriasis and psoriatic arthritis.

Then we have the newest category. The anti-IL-23 biologics. They’re really newest but the anti-IL-17, together I should say they’re both new. These have no risk for incurring tuberculosis, they have no risk for incurring candidiasis really, like the anti-IL-17s, although that risk is small.

The anti-IL-23s have a little or no risk for boosting inflammatory bowel disease. They’re safe in that category as well. Compared to the anti-IL-17s, the IL-23s don’t have a risk or less risk for candidiasis, and much less risk for inflammatory bowel disease. There even less things to worry about than the anti-IL-17s.

Downside of anti-IL-23s is that they don’t seem to work as well in patients with arthritis. Right now, at this point, with what we have in terms of studies, I would reserve the anti-IL-23 for people with severe psoriasis, like the IL-17, who don’t have joint disease.

The anti-IL-23s don’t seem to have as quick onset of action as the anti-IL-17s, but their advantage is that because it’s farther up on the pathway in terms of where the psoriasis trigger is, they have a lasting effect. They’re given every 8 to 12 weeks depending on the IL-23 antibody that you’re giving.

There are three basic anti-IL-23s that are on the market right now and more to come in the near future. They are tildrakizumab, which is given once every 12 weeks, guselkumab, which is given once every 8 weeks, and risankizumab, which is given once every 12 weeks. This is after induction doses. They have a lasting effect.

For people who are needle phobic, the two anti-IL-23s, risankizumab and tildrakizumab, are great choices. Just like ustekinumab, it’s given only four times a year. These are great choices for needle-phobic people. Now the way I break these down and choose among the three, they are very different in terms of the efficacy it seems.

Tildrakizumab is really for the more modest to severe, moderate to severe psoriasis patient who’s really needle phobic. Sort of taking place of a lot of the patients I used to have because it doesn’t have the IL-12, and it’s also four times a year.

The weight-based dosing is not that similar to ustekinumab, so you don’t have to worry about that, but I think it’s a good starter biologic. That’s the way I look at tildrakizumab.

Risankizumab, on the other hand, is a great biologic for severe psoriasis. It’s got a pretty quick onset of action, not as quick as the anti-IL-17s, in my opinion, but pretty quick as well. But, again, great lasting effect, half-life 28 days, but beyond that great lasting effect. The injections only have to be given four times a year which is well beyond the half-life of the product.

I look at risankizumab as great for severe psoriasis, no arthritis, we don’t have any evidence yet that it helps, that may be come in the future. We don’t have that now. Tildrakizumab is a starter biologic and guselkumab is something in between.

Let me summarize and talk quickly about the anti-TNFs, anti-IL-17s, and anti-IL-23s that we have. I discuss with patients the pros and cons of each. I use the anti-TNFs specifically in patients with more joint disease than psoriasis these days, where joints are more of an issue than the psoriasis.

Certolizumab has, like I mentioned, caveat for not crossing the placental barrier, so it’s useful in a woman of childbearing potential. Anti-IL-17s are secukinumab and ixekizumab. They’re great for quick onset of action, great for psoriasis and the joints.

The IL-23s are great for severe psoriasis. If it’s risankizumab, great as a starter product, if it’s tildrakizumab and guselkumab for somewhere in between. I think that’s the way to break them down. They’re all very different if you think about it. Please don’t let a PBM or insurer try and coax you into one or the other.

One thing is, brodalumab is the quickest onset of action of all and it’s great IL-17 for psoriasis as well as joints. That’s the way I work with my patients and how I choose among the biologics.

And, you discuss the pros and cons with each patient. I think that’s very important. The pros and cons of each biologic, the things I mentioned. And, you pick the one that fits their lifestyle best. Bottom line.

I like to give biologics time to work. The newer biologics, the anti-IL-17s and anti-IL-23s, I think, we’re used to even having more efficacy than we have with the anti-TNFs.

Still, I want to give the biologics a few months to see if it’s working because it’s a lot of work, as we all know, to select a biologic for a patient in terms of prior authorization and getting it shipped to the patient, and working with the patient’s insurer. So, we want to give the biologic time.

I don’t want to give it too much time because people who have psoriasis deserve to be clear. They deserve to have a much-improved disease because they’re suffering. But I think three to four months is a good amount of time.

If a patient is not PASI 75, or not about three-quarters clear, by that point, their psoriasis is not about, let’s just put it this way, 75% improved, I would consider switching biologics. That’s the way I decide whether biologics is good enough for a patient.

When a biologic is not working in a patient, there’s a few things you can do because, as I mentioned, it’s a lot of work to get that biologic approved.

I want to make sure that they’re about 75% improved before I decide whether to switch. If they’re less than 75% improved and close to that, we can add methotrexate to a patient.

If they’re close to 75% improvement or not quite there, or I’m using a lot of apremilast these days because I think it’s so much safer than methotrexate to give you that boost over, so apremilast and biologic where you’re not quite at 75% improved, you can try that for two months.

Because there’s a lot of work to change from biologic to biologic. We want to give the biologic we’ve chosen the maximal chance to work. I would only use these add-on therapies for several months because I like having just one medication personally in the long run if we can.

Apremilast, just like methotrexate, whether someone’s 75% improved in psoriasis or more, but the joints are still a bother, a lot of times I’ll use add-on therapy just for joints as well, especially apremilast these days.

You can add on to get a little boost if you’re not quite 75% improved or to treat joints when the psoriasis is already there. Those are two things. You don’t have to switch right away to a different biologic.

What factors determine whether you’re going to switch? I mentioned one, joint disease. What if the joints really aren’t improved at all but the psoriasis really is?

I had that for a patient recently who was taking one biologic, who was PASI 100, but their joints were killing them. We decided to switch to a different biologic. Maybe this patient’s psoriasis will get worse and won’t be completely clear and their joints will get better, we’ll have to find a happy medium. But that’s a reason to switch, is joints.

Another reason to switch is just if it’s not working, like I mentioned before, three or four months. Something else you can do, though, is trying to increase dosing. This is usually off-label because the doses of what we’re giving are usually FDA-approved. It’s hard to get off-label increased dosing.

When I’ve used increased dosing, I’ve done it primarily when there’s really no other choice that I think for that patient works. It’s difficult to get the extra medication for that patient. We usually have to go with samples for that. Increasing the dosing is not my first choice.

Really an add-on therapy temporarily is my first choice. Increased dosing can be used, like I said, temporarily, when there’s no other choice available because you have to get samples from the manufacturer.

I don’t usually switch to a biologic that targets the same pathway if things are not working, with exceptions. One exception is brodalumab. Brodalumab is an anti-IL-17, but it’s much more an anti-IL-17A like secukinumab and ixekizumab.

I’ve had multiple, anecdotally I’m telling you, again, multiple times with patients who are not doing as well with ixekizumab or secukinumab, and we switched to brodalumab and they’re doing fantastic. Because it is in the same anti-IL-17, but it targets much more than anti-IL-17A. It is anti-IL17 A, C, F, and IL-22. So, bunch of other things are targets.

Brodalumab is a much broader-spectrum medicine and will work on people where anti-IL-17s has failures. Never forget, the anti-IL-17s are a good choice for people who have psoriatic arthritis.

If they don’t, and say an anti-IL-17A is not working or anti-TNF is not working, switching to the anti-IL-23 is always a great idea. I think I would do that too. That would be for me more risankizumab because that personally seems to be the most effective of the anti-IL-23s. Like I said before, I reserve tildrakizumab as more of a starter biologic.

In summary, I would try and switch pathways and I would choose the anti-IL-23 pathway if the patient does not have much joint disease. And, say a patient is on an anti-TNF and it’s not working anymore, and they don’t have joint disease, I think risankizumab would be a great choice.

If a patient does have joint disease, an anti-IL-17 would be a great choice, whether it be secukinumab, ixekizumab, or brodalumab, and brodalumab especially if they want a broader spectrum with a quicker response.

I would switch an anti-IL-17 patient with joint disease, who is not getting clearance with secukinumab or ixekizumab to brodalumab because the anti-IL-23s, as far as we know right now, are not FDA-approved for joints, but we don’t have evidence that they work as well for joints. That’s how I would go with my switching.

I don’t think there’s any good data right now to determine which biologics patients will respond to, which therapies, or who may be treatment resistant. This is something that requires further investigation. I know it’s an active ongoing area of investigation.

Then we may, like I mentioned, chose a biologic because someone has more joint disease or verses psoriasis on the skin or vice versa, but we don’t necessarily know who’s going to respond to what.

This is an active way of investigation like I mentioned, and I look forward to finding out in the future, hopefully the near future, so we can figure out which target is best for that patient.

Because it certainly seems sometimes someone will respond to anti-IL-17 and not an anti-IL-23 or vice versa or not an anti-TNF, and one is like magic for the other. We just don’t have the information to determine that at this point.

In summary, some of the key takeaways are, most importantly, that one size does not fit all for biologic. If an insurance company is trying to peg you to use a certain biologic when you think it’s not the right choice for a patient, please push back.

They try and tell us that they’re all the same and their choice is the best because they know best, and that’s not the truth. They don’t know best. We’re the MDs. Even though they may have MDs working with them, their MDs do not have the experience that you have, and especially with that patient because every patient is different.

Certainly, they don’t have experience with the patient that we want that biologic for. That’s only where you can provide the best choice for patients. My first suggestion is to be persistent and pick the biologic you think is best.

We talked about how certain biologics may be better for certain patients even though we don’t know if that patient will necessarily respond to that biologic, but we have clues. We know anti-TNFs may be good for someone with more joint disease than skin disease.

We know that certolizumab is probably best used, and is the only biologic, I should say, compared to all the others, that doesn’t cross the placenta that we know, that’s useful for women of childbearing potential.

We know that anti-IL-17s are great choices for severe psoriasis and joint disease and are safer than anti-TNF. We know that anti-IL-23s are great medicines and risankizumab, compared to the others, is the most effective medication to treat psoriasis, but we don’t know about their efficacy in joints at this point. That’s the way I look at it and help pick and choose.

I like tildrakizumab, by the way, is a starter biologic. For someone who’s needle phobic and doesn’t have that severe psoriasis, not severe-severe, just enough for biologic.

That’s some of the niches that I’ve talked about in this podcast to help you select what’s best for your patient. Speak to your patient and tell them, again, what each biologic does and how it’s dosed and what they can expect and let them choose what they’re most comfortable with.

Thank you for listening. I hope this helps give you some patient profiles to select among all the biologic therapies and some ideas as where to go with a biologic for certain types of patients.

Remember, every patient’s unique and it’s really up to you, are the expert for finding what’s best for that patient, discussing with that patient.

Thanks for listening and please give us feedback. We love to hear from you.

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