Upadacitinib Versus Adalimumab in Psoriatic Arthritis

Among patients with psoriatic arthritis (PsA), treatment with upadacitinib (Rinvoq) led to greater improvements from baseline in Routine Assessment of Patient Index Data 3 (RAPID3) scores compared with adalimumab (Humira) from week 16 to week 56 and greater improvements versus placebo over 56 weeks, according to a post-hoc analysis presented at the recent American College of Rheumatology (ACR) annual meeting.

In this third of four exclusive episodes, MedPage Today brought together three expert leaders in the field: moderator Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, is joined by Melinda Gooderham, MD, MSc, of the SKiN Centre for Dermatology in Peterborough, Ontario, and Neil Korman, MD, PhD, of Case Western Reserve University in Cleveland, for a virtual roundtable discussion on the study findings.

Following is a transcript of their remarks:

Blauvelt: Hello everyone. My name is Dr. Andy Blauvelt. I’m a dermatologist and president of Oregon Medical Research Center in Portland, Oregon. This is a large clinical trial center. I also have a lot of experience taking care of psoriasis patients with and without psoriatic arthritis. Joining me today are Melinda Gooderham from Peterborough, Canada, who also runs a large clinical practice and clinical trial center, and Dr. Neil Korman from Case Western Reserve University in Cleveland. So, welcome to the two of you.

Today I just wanted to talk about what happened just at the ACR. And in this session we’re going to be talking about two particular drugs for psoriatic arthritis that you may not know as much about compared to the classic biologic drugs. So we’ll be discussing upadacitinib, which is FDA approved actually for PsA, and some new data coming from the ACR on upadacitinib.

The other abstract is going to be discussing some phase II data, longer-term phase II data for deucravacitinib [Sotyktu], which is a selective TYK2 [tyrosine kinase 2] inhibitor, so technically a JAK inhibitor, but a different type of JAK inhibitor that selectively attacks TYK2. So we’ll be discussing these two abstracts and how maybe these two new drugs are going to be fitting in the PsA treatment paradigm.

So the first abstract I’m going to describe briefly then ask for comments on is an abstract where patients were on upadacitinib 15 mg a day versus placebo versus upadacitinib 30 mg a day versus adalimumab. So there were four different groups — two different doses of upadacitinib, a placebo control, and then an adalimumab reference arm.

Now, what the authors did here was look at scoring from a patient-reported outcome called RAPID3. And so these are questionnaires that the patients were filling out in this trial. And RAPID3 encompasses several domains of psoriatic arthritis. It encompasses a pain domain from 0 to 10, a sort of a global assessment of improvement in disease also from 0 to 10, and then a quality-of-life measure from 0 to 10. So the total RAPID3 score is going to be 30 as the max, the worst possible disease in all of these domains, and 0 being the best.

And they gave some guidelines for assessing sort of the views of how to look at this RAPID3 data. So, if patients had a 3 or less that was considered basically doing great, the best possible score, 3 to 6 was mild, 6 to 12 moderate, and over 12 would be more severe PsA based upon this measure.

And so what they have found was actually over 56 weeks, the patients on upadacitinib 15 mg a day — so actually they didn’t report out the 30 mg data — but those on 15 mg a day actually did better in terms of this patient assessment of this RAPID3 compared to the adalimumab group. Pretty interesting for me. So that over the course of a year taking upadacitinib, they reported less pain, less impact on quality of life, more global improvement in their disease, when you compare these two, upadacitinib with the classic adalimumab.

So, I’m going to open it up now and get some thoughts. Melinda, what did you think of this particular abstract?

Gooderham: Yeah, I found it very interesting because of the quality of life. I’d previously seen the data showing that upadacitinib can have better effects than adalimumab, which as you say is a bit surprising, because in our minds, I think we’ve always thought adalimumab, gold standard. And then you come out with this pill that we are using even in other conditions and it’s actually working better for PsA. So to see the patient-reported pain, quality of life also improving, along with other efficacy measures, I thought that was pretty interesting.

Blauvelt: Yeah. How about you, Neil? What did you think of this one?

Korman: So I had some preconceived notions based upon multiple interactions with my rheumatologic colleagues who all say, “oh my God, this stuff’s a home run. This is the best drug there is for PsA. I’m using it almost entirely.”

Blauvelt: Interesting.

Korman: So it’s nice to see that the data supports their opinions … you’re asking how we see it. I haven’t seen enough people on upadacitinib for PsA to be able to comment from my experience, but from my colleagues who treat a lot of PsA, the answer is this is a great drug. This is a top of the line drug. And, so yeah, we have to rethink our idea that TNF [tumor necrosis factor] is the holy grail, gold standard for PsA.

Blauvelt: Yeah. In fact, I go so far as saying that I think the launch of upadacitinib for PsA was really low key and not hyped. And we’re all psoriasis experts and I’m going to admit that when upadacitinib was approved for PsA, I didn’t know about it for awhile, and it took me some time, and when it got approved for atopic dermatitis earlier this year, everyone would say, “oh, by the way, it’s been out and it’s approved for PsA as well.” And so I had to kind of go backwards a little bit and think about it and learn about the upadacitinib PsA data. I don’t know if you guys are using it much, but I just think that its just been kind of a low-key introduction in the PsA field. I don’t know if you feel the same way.

Gooderham: A hundred percent, same as you. I found out after the fact, and when I saw the data, I was like, wow, how come I didn’t know this?

Korman: Well, the problem though is that the three of us don’t treat a lot of solely PsA. Okay? So that’s why we’re not going to have a lot of this drug because it doesn’t look particularly exciting for straight psoriasis. So it’s much more common that we’ll see a patient who has really bad psoriasis and, you know, bad enough psoriatic arthritis. So that’s not a patient for this, the patient for upadacitinib is someone who’s got bad psoriatic arthritis and barely noticeable skin disease.

Blauvelt: Yeah, interesting. So I do know also that the drug has not been picked up as much as maybe as the company would like for atopic dermatitis. And there the data looked terrific to me, to me it has the best efficacy of any drug for atopic dermatitis, but I think it’s because of safety. And dermatologists have been shy over the labeling in upadacitinib. … How are you describing safety of this drug when you’re considering using it in one of your patients?

Korman: So what I do is, in my mind’s eye, I am using this drug for my atopic patients. And now another drug, another JAK inhibitor, for the alopecia areata patients, I’m thinking the best patients are the ones who are the youngest and the healthiest and have the least comorbidities because of all the noise and hype around the ORAL Surveillance study where the JAK inhibitor safety profile got stuck onto everything, even drugs [for which it] didn’t occur.

So, this is a study in rheumatoid arthritis that was demanded by the FDA, I don’t know, 6, 8 years ago when tofacitinib [Xeljanz] came to market and they tried to look at both 5 and 10 mg doses and the FDA didn’t like what they saw for the 10 mg. So they approved the 5 and they said, go do this study. So the study was done, it was finished, I don’t know, a year ago. And maybe 9 months ago or something, the FDA came up and said, well, here are all the warnings for tofacitinib, but P.S. these warnings will all get applied to every other JAK inhibitor that currently exists or that ever exists in the future. And sadly even to a topical JAK inhibitor.

So, a bit rough and this is why most of our colleagues are unwilling or afraid. And I warned my rep, I said, don’t hold your breath. You know, maybe you’ll see two or three of these in the first 3 months. Don’t expect a lot.

Blauvelt: I think it’s unfortunate, in my opinion, because those patients were just so different than our patients. They had to be over age 50, they had to have at least one cardiac risk factor, and 75% of them were on either methotrexate or prednisone in addition to the tofacitinib. And then we get the safety in that population. And as you guys know for the dermatology diseases, JAK inhibitors were monotherapy. They tend to be much younger patients, healthier. And we just haven’t seen the boxed warnings play out in the derm diseases, except for, in my opinion, the serious infection data.

So, to me, we do see a serious infection signal in the derm conditions as well, but we’re not seeing cancer, death, venous thrombosis, and what’s the other one?

Korman: Cardiovascular disease.

Blauvelt: And MACE [major adverse cardiovascular events] in the derm diseases, or at least hasn’t played out yet. So I think it’s unfortunate. We’re kind of stuck with this labeling. Yet I think that drugs are going to turn out to be safer than, definitely safer than, what we saw with the rheumatoid arthritis population, and maybe comparable to other drugs that we use in dermatology and that we don’t have problems with.

So, Melinda, what’s your take on safety and JAK inhibitors?

Gooderham: Completely agree. Actually, it’s done really well in AD [atopic dermatitis] in Canada, actually, upadacitinib, quite a number of people are prescribing it. And when we have meetings, everyone has cases to discuss. So I think we are getting some experience and completely agree with you. The only thing that I’ve seen are some infections. Herpes infections. A lot of people on either reactive or proactive antivirals, and a couple cellulitis, but none of the other issues, the more rare things. And, again, younger population, no pre-existing risk factors.

But that is what I do discuss with my patients. You might have increased risk of infection, here is your prescription for your antiviral when you need it, call me if you’re having other issues, if you need an antibiotic.

Blauvelt: Yeah, I think dermatologists, for me, my opinion is that they’re going to have to learn how to use this class of drugs. We have psoriatic arthritis indication, we have atopic dermatitis indication, we have alopecia areata indication, we have a vitiligo indication for topical use — it’s just not going to be good if they say, no, I don’t want to use this class of drugs. It just seems like they’re too important, kind of new drugs in our armamentarium for a wide variety of things where we don’t have much to offer. And I think, coming back to PsA, it’s nice to be able to offer, I think, a nonbiologic option for patients who are having continual problems with their joints.

Watch episode one of this series: Safety and Efficacy of IL-17 Blockers for Psoriatic Arthritis

Watch episode two of this series: IL-23 Inhibitors for Psoriatic Arthritis

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