Ana-Maria Orbai, MD, MHS

 Ana-Maria, you want to handle number 3 and we’ll wrap this up?

: Thank you. A 57-year-old gentleman presenting with severe plaque psoriasis as well as large joint arthritis, knees, intermediate involvement at left elbow, left ankle. Has had psoriasis since the age of 23, you’re looking at 30-plus years of psoriasis. Treated with topicals, had some improvement with topicals. He had no arthritis at the time of his diagnosis with initial psoriasis, but he got this arthritis fairly recently, 2 months prior to the visit that he got this asymmetric polyarthritis. Past medical and family history unremarkable. Had a screen test, and he then went on, he had some metabolic, CBC [complete blood count], and what not. He was started on methotrexate, 15 mg weekly, we’ll say it’s oral, some small amount of a physiologic dose of prednisone, 7.5 mg daily. He takes that for 2 months, has some clinical improvement. LFTs [liver function test] go up, that’s 4 times the upper limits of normal, right at the 120s for transaminases. They stopped the methotrexate, and they add sulfasalazine, 1 g BID [twice a day]. After 3 months of sulfasalazine, he had some mild improvement of the skin manifestations, but knee synovitis persisted, and CRP [c-reactive protein] still elevated.

We got into treatment on this one a little bit quicker, but impression, any recommended testing, and then what factors would perhaps play a role in the treatment options, and would you ever go down the methotrexate pathway again. Go ahead and give me your thoughts on that, Ana-Maria.

: This is a man with severe disease and possibly undertreated disease. It looks like he’s had severe plaque psoriasis for 30 years prior to this development of arthritis, and in my opinion, he’s developing this arthritis a bit late in his disease course. At age 57, I would definitely look for other types of arthritis, particularly gout, could this be pseudo gout? I would x-ray the large joints to look for calcifications and I would refer him to our musculoskeletal ultrasound clinic to make sure that I’m not missing erosions typical of gout, for example, or that I’m not missing entheseal changes typical of psoriatic arthritis. I would use a few modalities to be able to categorize this with more certainty, the inflammatory arthritis belonging to psoriatic disease.

The other piece could be that he’s been underdiagnosed with this arthritis and he’s had low levels of joint inflammation and we’re diagnosing it late altogether. He’s been using prednisone and methotrexate, and prednisone can I would say mask the joint disease. My concerns with this patient, and then he’s developing complications. He has liver function test elevation. First, I would confirm the type of arthritis that he has to be able to guide treatment. Second, I would diagnose his liver disease. Is he using concomitantly other hepatotoxic things? Is this Tylenol? Is this alcohol, or is it fatty liver associated with psoriatic disease? I would send him to an ultrasound, definitely would stop methotrexate. This would not be somebody I would rechallenge with methotrexate. I’m not sure I would have started sulfasalazine in the first place, and I would be surprised how sulfasalazine helps with his skin because that doesn’t usually happen. Assuming that he has inflammatory arthritis, which I think he has, psoriatic arthritis, then I would go right away to a biologic with 2 priorities: 1., to bring his disease activity down, and 2., to get him off of prednisone. These would be my 2 urgent objectives with this patient. I don’t think we necessarily have a specific indication for 1 biologic vs the other in this case. As Len said earlier, the options are wide open. He does need to get on something else.

: Assuming the liver calmed down a little bit, assuming his liver was from the methotrexate, which again, not knowing all the details, but it sounds like his baseline labs were fine. Someone gives him methotrexate; the liver goes up. Unless he’s starting to drink heavily, take Tylenol, it’s probably from the methotrexate, so I agree with you. Let’s say his liver was persistently high, would you maybe go down another MOA [mechanism of action] vs another, and it’s tough to know.

: I agree with Ana-Maria. First of all, getting 3x LFTs at 8 weeks on methotrexate, he’s got liver disease of some sort or he’s drinking heavily or something like that. He’s got cardiometabolic tendencies, and that’s a high priority. If he was going to get treated, he’s 57, you would avoid things like infliximab [Remicade], etc., and you’re wide open otherwise. That is a very significant finding and probably will represent a comorbidity that we’re going to have to deal with somewhere along the line.

 I think we’d all agree, no sense in rechallenging with it in that scenario.

: Prednisone, treat by the prednisone 7.5 mg. We may not all admit it, we all sometimes have to play with it, but what are your thoughts on that, Sheetal? You’re looking at 7.5 mg daily for 2 months and then they say…so 5 months for this patient. That alone would have led you to go down not necessarily the sulfasalazine pathway, unless this patient just was absolutely refusing biologics. What are your thoughts on that, Sheetal, the oral prednisone?

: Yes, we do avoid it as much as possible, but I know we all use it at some points. I will say that if I had to think of a number of patients that I truly felt had psoriasis, psoriatic arthritis, that I’ve started prednisone on, it’s on 1 hand how few times I’ve done it. Every time I’ve done it was because they needed some functionality and they couldn’t get their drug and they had to. We’ve always paid a price as we taper them off of it, that they had a lot worse manifestations of their disease with psoriasis. Yes, I try to avoid that. That’s a good amount of time for him to have been on the prednisone and I agree, it seems like most of the conventional synthetic DMARDS have already been tried and this is someone that you’re going to go to a biologic like Ana-Maria said. That’s what you’re leaning toward and I don’t see anything that would make me choose one biologic over another.

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Ana-Maria Orbai, MD, MHS, leads the discussion on a real-world case scenario of a 57-year-old man who presents with severe plaque psoriasis and arthritis and shares clinical impressions as well as therapeutic goals for the patient.

Case 3: 57-Year-Old Man With PsA

Another case, case number 2. We’ll have Sheetal run this one. A 26-year-old female coming in with a near history of pain in multiple joints. Pain started in the knees with some mild intermittent swelling, a fairly insidious onset of pain, and then over the next 2, 3 months, it migrated to involve the symmetric ankles, elbows, feet, and shoulders. She complained of some persistent inflammatory low back pain—so they actually call out inflammatory low back pain—associated with morning stiffness going on for about 2 hours. Then for the past month before coming, she has developed these lesions that seem to spare the face, the palms, and the soles. She complained of some fever and fatigue. On exam, she had some mild knee tenderness with some mild swelling, MCP [metacarpophalangeal joints], PIP [proximal interphalangeal joint], pretty diffuse involvement. They don’t talk much about the skin exam, but we’ll assume that the lesions are where they said they were. Routine blood testing, the CBC [complete blood count], comprehensive metabolic panel were normal. CRP [c-reactive protein], SED [erythrocyte sedimentation] rate was elevated, RF [rheumatoid factor] was negative. The only imaging result we have thus far is a hand radiograph that showed right second PIP erosion, and then right fifth PIP fixed flexion deformity. We have intermittent history of exam here, but that being said, initial impressions, testing, then of course looking at the fatigue part of this as well. Give me some thoughts on how you would start approaching this patient.

: If I’m pretending a fellow is presenting this patient and coming out of the room, I would say, it’s a young female, 26-year-old, around the age that we would see psoriatic arthritis about, close to 30 years old, 30 to 50, 1 to 1. Even though the last case was female and she’s female, we see it with equivalent levels in both men and females. The arthritis has been going on for some time. We have a chronic arthritis that has an inflammatory component, symmetric polyarticular arthritis, like the old Moll and Wright criteria would be RA [rheumatoid arthritis] -like in this situation. She also has inflammatory back pain with prolonged morning stiffness. This patient has psoriasis only over the last month, but I guess she’s had a year history of inflammatory arthritis. I would focus on how psoriasis does precede the majority of patients who get psoriatic arthritis approximately 70% of the time, but in a minority of patients, 15% of them, the psoriasis and the arthritis can present simultaneously, and then in another 15%, you can get the psoriasis after they have the inflammatory arthritis.

She has significant fatigue. She is CR negative, rheumatoid factor, has elevation in her inflammatory markers, and after 1 year of disease, she has an erosion seen on radiograph, and has ankylosis. It’s concerning to me that this is somewhat of a rapid progressor with significant polyarticular symmetric psoriatic arthritis with a good amount of progression. I would feel comfortable with the diagnosis of psoriatic arthritis here. For further testing, I’d recommend some imaging of her sacroiliacs, of her spine if she complains of any other areas like cervical disease just to get an idea if we can find inflammation and finding sacroiliitis.

When it comes to the treatment regimen we would recommend, it would be reviewing the domains involved. Her domains involved are her peripheral arthritis, she has axial involvement, she has skin involvement. She has no mention, at least in this stem that I’m reading right here, of dactylitis or enthesitis, although I find that unless you go looking, you won’t find it. I find the more I look for enthesitis, the more I find enthesitis. But currently, the domains based on the stem we have are peripheral joint, axial inflammation, and skin. There’s no mention made of nail changes. It would be going along the lines of agents that would work in these areas. Because we have axial involvement, we would be straying away from the conventional synthetic DMARDS [disease modifying anti-rheumatic drugs]. In this patient we would be looking at a combination of, for her arthritis, possibly NSAIDs [nonsteroidal anti-inflammatory drugs] plus a biologic, but for her skin disease, it would be the biologic. The biologics that I would consider here, I’m not reading any concerning features of demyelination as a comorbidity or inflammatory bowel disease symptoms, but we do need to ask them if they have any diarrhea, mucus, or blood in their stools on a frequent basis. If she doesn’t, then I would be open to anything along the lines from a TNF [tumor necrosis factor] or an IL-12/23, an IL-23, IL-17. There’s nothing that’s stopping me from consideration. One would argue that given her axial involvement, though, maybe we would put the TNF and possibly even the IL-23 family a bit higher than the other families.

: They call out the fatigue as well. There’s some consideration, but they all do a good job. It’s interesting that they call that out.

: Right, this is how I think through it. It’s nice that we have some data on the IL-23 MOA [mechanism of action] with the guselkumab [Tremfya] with fatigue. My hope, as Len said, that we’ll start to look at some of these more patient important metrics in the future clinical trials in PsA [psoriatic arthritis].

: This case is nice because it asks the question of how would you differentiate her pain and fatigue from fibromyalgia? This is important. This patient, this woman clearly has inflammatory disease. She has clinically inflamed joints, she has elevated inflammatory markers, I would say that even if she has overlapping fibromyalgia, this is not so relevant because it’s not going to influence my choice of therapy. It can complicate measuring improvement down the road, but I don’t think that this would be particularly relevant at the first visit because she would also be in pain and fatigued due to her active disease.

: Thank you for highlighting that, Ana-Maria. I agree with you. In this situation, differentiating the pain and fatigue from her inflammatory conditions vs fibromyalgia is clearer because she has a clear inflammation that becomes much grayer when they don’t have much inflammation on exam and then they have these metrics and you’re trying to figure out what it is. Len, were you saying something?

: Yes. I would only add, in fact I agree with everything, it’s a first visit and you know how you’re going to start this therapy. She probably has fibromyalgia and that may become more important down the line as Ana-Maria said. I would get more aggressive earlier in sorting out this inflammatory back pain and whether this is like the pseudo fibromyalgia of spondyloarthritis that we’re trying to understand in young women. Maybe she has a mixed picture of this. Obviously, we’d start with a pelvis film and maybe somewhere down the line, if it was negative, get MR [magnetic resonance] imaging of this. But I agree with everything otherwise. Right now, she has clearly inflammatory disease and needs to be treated.

: First off, sometimes when you see this much of inflammation in a particularly young patient, female or male for that matter, and they do describe IBP, inflammatory back pain, that well, I start believing it more, which is not necessarily fair. You almost start reading into the most subtle changes on the radiograph that you might not otherwise. But, with what’s going on peripherally, we need to be thinking fast that she’s going to be needing something beyond just most likely a conventional DMARD. But I agree, there’s a lot on the checklist to do that first visit, but, at a minimum, getting a radiograph of the sites.

Sheetal Desai, MD, leads the discussion on a real-world case scenario of a 26-year-old woman with polyarticular symmetric psoriatic arthritis and shares her approach to treatment.

Case 2: 26-Year-Old Woman With PsA

Let’s move on to some cases. We’ve got 3 total here. The goal with these “real-world” scenarios is to bring up some interesting tidbits that may come up in clinic, with some comorbid issues and the like. I’ll go ahead and read them out, and we’ll start with Len Calabrese on this first one. This is a 31-year-old Caucasian female, presented to her PCP [primary care physician]. She had some body aches, some difficulty in picking up her child and some of her ADLs [activities of daily living], like cleaning the house. She’s had scalp psoriasis for 6 years, it looks like shampoos had controlled it well. She also had this prior history in her records that talked about some questionable multiple sclerosis [MS].

Physical examination showed some synovitis over the elbows, some PIP [proximal interphalangeal], in the MCP [metacarpophalangeal] joints. She also had some right-knee synovitis. On our neurologic exam, there were no sensory deficits or hyperesthesia; there was not a very accurate motor exam as the patient had some limitation on active range of motion. On imaging, she already had some asymmetric erosive changes in the small joints in the hand, some joint space narrowing in IP [interphalangeal] joints. On laboratory tests, she had elevated CRP [C-reactive protein], modest elevation in SED [sedimentation] rate; let’s make her negative ANA [antinuclear antibody] and rheumatoid factor. That being said, Len, do you have any impressions, further thoughts and maybe treatment thoughts in this regard?

This is a relatively young woman, and she clearly has what sounds like documented psoriasis. I don’t see anything on this exam at this time, but let’s assume this is bona fide psoriasis. She has arthritis, and she has multiple tender and swollen joints, and alarmingly, she has erosions at baseline for our encounter. She hasn’t been on any therapy other than topical, so she’s in a wide open space. The fly in the ointment here is the “history of multiple sclerosis.” That may be real, it may not be real. This is often a difficult disease. This generalized achiness, I don’t see anything on her exam about generalized soft tissue tenderness. When I hear this questionable multiple sclerosis, that usually means a person has some type of fatigability, intermittent, either dysesthesias or pseudo dysesthesias, so that’s in my mind to sort that out.

This person is in trouble. She’s young, and she already has an erosive disease and needs therapy. The first thing I would do, among other things, she’s already been x-rayed, her exam is done; you’re assessing comorbidities here. I don’t hear anything about any bowel symptoms. I don’t know what her habitus is, if she’s elevated BMI [body mass index]. She deserves some baseline lipids even if she’s only 31. I would screen her with a metabolic profile and a hepatitis profile because she’s going on to some type of therapy. I’d go into that MS [multiple sclerosis] deal a little, and if it had a high pretest probability, I’d send her to neurology to have that sorted out. Let’s say she believes she has multiple sclerosis, or somebody has documented this, that’s a fly in the ointment in the progression.

That would be my work-up, and then we’ve got to start talking about picking some therapies here. Let’s say that we can’t rule out the MS at this time, but she’s in distress, she has erosive disease. I would start her on methotrexate, and she’s probably going to escalate to a biologic, but she’s got to go down this road. Methotrexate and multiple sclerosis go together just fine. There are some soft data that it may be helpful. Try to get her on this for 3 months and educate her, and see what’s going on. Anybody else have strong feelings any other way?

: I agree. If she does have some questionable MS because of the demyelinating concerns, historically with one of the other TNFs [tumor necrosis factor inhibitors] in development in the 1990s, we have to avoid the anti-TNFs here. You’re going to be starting with methotrexate, which I feel like we all still do, start methotrexate in the majority of our patients before we rapidly go on to biologics, depending on how the patient does.

: It’s so tough, the MS paradigm; this is just a scenario, but it does happen. You’ll see it with these EMRs [electronic medical records] and 50 diagnoses, and you don’t know which is what. Same thing with inflammatory bowel, which is really just irritable bowel, but you start wondering and ask, “Who’s your GI [gastrointestinal] doctor?” Well, “I don’t have one.” “Who’s your neurologist?” They say, “I don’t have one.” “Did you ever see a neurologist?” “No, I never saw a neurologist.” We trust our patients; we listen to our patients. It’s hard to not see something like that on the chart and go out, I’m not one to sit there and start imaging the brain. I’d need neurology’s help. But a nice little look at her records, I hope we had a primary care provider who at least sent them our way.

: Yes, with who made the diagnosis. I agree. We’ve put that up there, it needs to be sorted out.

: Let’s assume, again, as Sheetal was saying, the nice thing about living in 2021 is we have NOAs [notices of admission]. If this was 2009, it would be a bit more challenging. But a good case. Ana-Maria, anything on your end? Do you have anything to add to this particular scenario?

: This case is not unusual. If we all mentally think through the CASPAR criteria and we did our due diligence, we checked rheumatoid factor, we checked anti-CCP [anti-cyclic citrullinated peptides] to rule out rheumatoid arthritis. This young woman is unlikely to have gout, especially with this presentation with MCP, PIP, DIP [distal interphalangeal], large-joint arthritis. I would not hesitate to go to an IL-17 [interleukin-17] inhibitor or an IL-23 inhibitor in her case. I would initially overlap with the methotrexate. If she didn’t achieve remission in those 3 months, with this burden of disease, in my experience I’m not sure we can expect her to achieve remission in 3 months with methotrexate. I feel this is someone who is going to need more therapy.

: And an IL-17 inhibitor is right there. I would just grab it.

Leonard H. Calabrese, DO, leads the discussion on a real-world case-based scenario of a 31-year-old woman with psoriatic arthritis and shares clinical impressions.

Case 1: 31-Year-Old Woman With PsA

: We’re going to wrap up this section. Ana-Maria, can you talk about some concepts about switching therapies? It’s not always an easy topic. What are those circumstances, for example, not enough efficacy and tolerance, do you go with the same class or move around? Give us your thoughts on that, Ana-Maria.

: This is a very frequent question in the clinic. Our therapies don’t last forever, even if they’re a good match with the patient’s phenotype. Even if there’s a good response initially, they can have secondary failure for various reasons, whether that’s because they develop antidrug antibodies, or maybe the disease finds a way to overcome the mechanism that we’re inhibiting, and then we have to press a different button. Our ability to measure the reasons why patients are failing therapy is not so great. We have antidrug antibodies for a few therapies. Unfortunately, studies of strategies of measuring drug concentration and antidrug antibodies, if anything, have been discouraging us from measuring them; although I’m still curious and I think it’s helpful for some patients. It’s going to happen in clinical practice, and depending on our judgment with the patient, we may be staying in the same family or maybe switching the mechanism of action [MOA].

A more concrete example is if somebody has secondary failure, but otherwise had an excellent response to a TNF [tumor necrosis factor] inhibitor, there’s no reason to not try a second TNF inhibitor, if they responded and did well initially. If there are new disease manifestations, for example, somebody who had, in principal, arthritis, maybe mild psoriasis, and all of a sudden they have worsening of their psoriasis, so their phenotype is worsening or we see new manifestations, then I would be more tempted to try a different mechanism of action, an IL-23 [interleukin-23] inhibitor or an IL-17 inhibitor. As we discussed earlier, it’s not a one-way street.

Following disease activity and the patient’s course is very important. It’s an experience-based decision and shared decision-making with the patient whether we’re going to continue doing the same thing or similar things that we’ve done, or are we going to switch mechanism of action? Switching the mechanism of action has been my go-to approach. I find myself more often doing this because we have these choices. You’re thinking, if now I press a different button, I’m going to get more results, and that’s what I’m seeing in my clinical practice. In full disclosure, I feel that I have patients who have worse skin disease than most other clinics, but there’s variation here. Any other thoughts?

 It’s not an easy answer, looking at the clinic data. I had 2 patients who came from dermatologists, and it’s always that classic question of, “Look, their skin did great. Their joints, they’re not really good. But, oh my god, their skin is great.” Some of the dermatologists, I don’t like to use the word flip-floppers, but they love to rotate their MOAs, and they’re comfortable doing that a bit too soon. What happens to me a lot of times is when someone has found that, and some of these people have horrific skin involvement, when their skin is just beautifully done, it’s hard for the rheumatologist, or anyone for that matter, to say, “We’re going to switch over to this one. Pray that your joints get better, and I hope your skin continues to do well.” Now fortunately, with some of the new MOAs, the skin part is OK, but switching is not always easy. They have to come off their therapies, there’s that period of potential flare with switching therapies, and there’s no guarantees when you switch over.

I was going to ask others, either Len, Sheetal, or Ana-Maria for that matter, do you find—because there are some who still do this, they are fine adding a conventional DMARD [disease modifying antirheumatic drug] to, for example a TNF, a monoclonal, if the dermatologist didn’t have them on it, but their joints are not doing that great, not necessarily dactylitis. Do you all find that adding, say methotrexate—they hadn’t been on methotrexate, they’re not on the drug from a psoriasis standpoint—do you find adding a conventional DMARD helps in some cases in PsA [psoriatic arthritis]? Len, I’ll let you go with that.

: If your TNF is failing and it’s arthritis, you’re in big trouble to begin with, because the other agents, while they’re all good, none of them are superior to a TNF for particular disease. That would be my natural inclination, to add a conventional synthetic DMARD in that setting, if the patient is up for it. We’re talking arthritis here, and I’d be interested to hear what Sheetal and Ana-Maria have to say.

: I would agree, and I would say that we have a dermatology room clinic, and we have patients, as you guys said, who are rapid cyclers from the dermatology side, who have tried many agents. Once they get to the agent that works amazing on the skin, and it’s had some efficacy in the joints, but it’s not as great, especially if they’ve been a rapid cycler, I will add a DMARD to see if I can boost the efficacy of the joints. That way they can stay on the same agent. We all get this. We’ve had patients who have cycled through practically every drug, and then you wonder if they were on the drugs long enough, and you feel like you have to go back to the beginning and reevaluate again. I do find that I add the DMARD. I will say that I don’t add the DMARD for the arthritic component if they have absolutely no benefit in their arthritis. Let’s say their skin improvement is above 50%, 60%, 70%, and they’re happy, and their joint improvement is about 30%, 40%, and I’m trying to boost it, then I will consider adding a DMARD.

: I’ve been fascinated also, and sometimes you’re lucky when it happens, but something as simple as an NSAID [nonsteroidal anti-inflammatory drug], while I know we have all the comorbid issues with that. But it’s fascinating when you have a 32-year-old who says, “No one told me about” a certain anti-inflammatory, and that’s just enough to cover that. It’s clearly not disease modifying, but [we try] every trick we can. Again, switching therapy, and it comes up, it’s what we do. I tell patients there are no guarantees, particularly someone who’s been rapidly cycling through, sometimes in dermatology, sometimes rheumatology, but I’ve seen it a lot on the dermatology side.

: How many times do you feel like it’s a game of tag? We think it’s a psoriasis, then I tag the dermatologist, and now the psoriasis is better, and it’s the arthritis. It’s like a game of tag, you’re it, you feel like you’re constantly going back and forth with some patients. I feel like the number of patients who get amazing improvement in both skin and arthritis is lower than what I would expect.

: It’s lower than what I would expect from seeing clinical trial data and everything. In reality, it’s that they get an amazing response in one and a good response in the other, and then it’s weighing for the patient what’s more important for them and their functionality.

Ana-Maria Orbai, MD, MHS; Anthony M. Turkiewicz, MD; Leonard H. Calabrese, DO; and Sheetal Desai, MD, comment on the appropriate circumstances to switch therapies for the management of psoriatic arthritis.

Ana-Maria Orbai, MD, MHS

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