There are many challenges, as most rheumatologists know, dealing with rheumatic diseases, and this is true even prior to the pandemic. Our diseases are often challenging to diagnose. They’re multifaceted, and we lack all-encompassing diagnostic tests that are both absolute sensitive and specific; we have to rely on clinical diagnosis, and that’s not always easy. That’s one of the enjoyments of our field as well, but certainly this is challenging.

Once we’ve made a diagnosis, we have chronic diseases without cures, and although our treatment options have expanded in many different diseases, we still don’t know what treatment a particular patient is going to respond to best. When we’re thinking about first-line therapy or sequential therapy, second, third line, we don’t have a diagnostic test yet that will help us predict which drug is the best for that particular patient. Similarly, as I mentioned, our diseases are multifaceted and complex, so assessing a patient is equally challenging.

Determining how our patient is doing on therapy can be very time consuming and tedious, and we would benefit if we had biomarker that gave us a snapshot, a global assessment of how our patient is doing. That would help aid and facilitate our treatment of these patients in the COVID-19 [coronavirus disease 2019] setting. Although our treatment options have expanded in many different diseases, we’re still lacking treatment options in many of the diseases we treat.

The good news is there are a lot of clinical trials ongoing in some of these diseases, and it looks like in the future we’ll have more treatment options. Once we’ve picked a treatment option for our patient, and even when they’re responding, patient adherence and compliance is often an issue. Also, one of the biggest challenges we are continually facing is accessibility and costs associated with these medications.

The goals of therapy and the factors that guide therapy in patients with psoriatic arthritis are many. Each patient we’re confronted with in that room in that moment is different, and our treatments are individualized. We really have to have a good appreciation that this is a heterogeneous disease; it’s multifaceted. Each patient is unique.

The things that we look at are the domains that are involved specifically to psoriatic arthritis. We’re looking at skin involvement, peripheral joint involvement, spinal involvement, enthesitis and dactylitis. We’re looking at the severity of several symptoms within each domain. Specifically, we’re often looking at the severity of skin and joint involvement to help guide which treatments we may choose. We’re keeping this in the back of our minds, and we’re rapidly trying to formulate which is the best therapy.

We’re doing that in the context of other factors, such as comorbidities. Does the patient have inflammatory bowel disease [IBD]? Have they been diagnosed formally with inflammatory bowel disease, or are you suspicious that they have inflammatory bowel disease? That often happens as well. We see patients who have not been formally diagnosed with IBD, but they give this long-standing history of their abdominal pain, bloating, diarrhea, and maybe even mucous in their stool and sometimes even blood, but they’ve not been formally diagnosed.

Here we’re thinking that the patient may also have inflammatory bowel disease. They may have more subtle symptoms as well. They may provide a family history as well. This is one of the comorbidities that we think about. We also think about other factors, such as previous history of infections, diabetes, fatty liver disease. Then obviously we must factor into the equation patient preferences. Does the patient want an oral agent? Do they want something that they can self-administer at home?

Are they OK with subcutaneous injections? Do they prefer something that is administered by a health care professional, and the frequency of administration of the treatments. We also must look at what have they tried and failed in the past? Are there data that can help us guide our treatment decisions in terms of clinical trials, looking at failed therapies in the past, and what agent we should use next?

For those of you practicing rheumatology, you know that our field, our specialty, is challenging. This was true even prior to the pandemic that we’re in. Barring the issues that have come about with the pandemic, there are many challenges in the practice of rheumatology and treating our patients with rheumatic diseases. To begin with, we are often confronted with the fact that we don’t have all-encompassing tests that are very sensitive and at the same time specific to be able to accurately diagnose our patients with particular conditions.

A lot of our diagnoses are based on clinical judgment, classification criteria and diagnostic criteria, so there’s some room for practicing the art of medicine. This is one of the enjoyable parts of our specialty, but at the same time challenging in terms of making a definitive diagnosis many times. Once we’ve made a diagnosis, we’re very fortunate that in many of our diseases the treatment options have expanded in the last several years.

We are left in many diseases without treatment options, but the good news is there are a lot of clinical trials in progress even within these diseases, and so there may be hope in the future with some of these diseases that we don’t have approved medications for. In terms of the diseases for which we do have treatment options, we still don’t have cures. We are confronted with the fact that our patients have chronic diseases without cures, and we don’t often know what is the best therapeutic option for that patient.

We don’t have a way of predicting what drug a patient is going to respond to best as first line or as second or third line as we sequentially treat these patients with various agents; this is also another one of our challenges. Another of our challenges is that our diseases are oftentimes multifaceted, and our assessments of these patients can be very cumbersome, very time consuming, and require a clinician to be a good clinician.

It would be nice if we had biomarkers that would give us a global assessment of how our patient with a particular disease is doing, and we could base changing therapy or continuing therapy based on perhaps a number. That would be helpful for us. Some of the more common challenges that we deal with also include that our patients are oftentimes not adherent to medications for a variety of reasons.

We’re very fortunate that our treatment options have expanded. We have many FDA approved drugs within different diseases, and over the years these treatments have become very targeted, very select. They oftentimes can produce good results, and they’re cleaner, perhaps, than some of the drugs that we were using in the past that were not specifically developed for those particular diseases. In general, our efficacy has improved, our toxicity has reduced, Despite that, patients are oftentimes not adherent with therapy over the long term for a variety of reasons.

Studies support that, when you look at claims data, that patients often do not refill their medications or stay on therapy for a variety of reasons. This may include loss of response over time. It may include [adverse] effects. It may include coverage issues. It may include that the patient is feeling good and decides to stop therapy because they’re feeling good. I’ve seen that happen many times as well.

There are a variety of reasons that patients might not be adherent to medications. A lot of times patients are concerned about [adverse] effects. They haven’t experienced [adverse] effects, but they’re concerned about potential [adverse] events that they’ve heard about on TV, they’ve read on a package insert, they’ve heard from their pharmacist or other people. So they start to perhaps deviate away from the intended use of that drug, and they start to vary in terms of frequency of administration and so forth.

Last but certainly not least, one of the biggest challenges we face is that the drugs we have are often very costly. Although there are a lot of different avenues available to help reduce the out-of-pocket costs, there is significant cost associated with these medications. There are issues in terms of cost, coverage, and accessibility. There are always issues with insurance formularies, prior authorizations. There are always these continuous challenges despite the fact that we do have effective therapies for a lot of our patients.

Rheumatic Disease Challenges and Goals of Therapy

 I had the honor of presenting at this last ACR Convergence [American College of Rheumatology annual meeting]. It was a unique but pleasurable experience being able to present virtually from my home. I was able to present and enjoy being a part of the meeting and attending sessions myself. I presented on treatment options for patients with psoriatic arthritis.

When we’re confronted with patients with psoriatic arthritis, the decision for treatments can be complex. We’re fortunate that our treatment options have expanded in the last several years, and we have a lot of options. Because of that, we can afford to be choosy in terms of what treatment option we want to pick first, and certainly as we pick different options sequentially after patients have tried and been intolerant to or failed various treatments.

Typically when I’m confronted with a patient with psoriatic arthritis, I fully appreciate that this is a heterogeneous, multifaceted disease, so I want to get an idea of what is going on with the patient in terms of domains that are involved. Do they have skin involvement, and how much involvement? Do they have peripheral joint involvement, and how severe is that? We look at enthesitis and dactylitis and spondylitis and nail disease. And again, we look at the severity of each of these domains, and we refer mentally to our knowledge of different treatment options and how they work within each of these domains.

We think about what’s the published literature? What’s our clinical experience with these different treatment options in terms of response within each of these domains? We also must take into consideration if there are data to support radiographic inhibition, if that patient, we feel, is at risk for radiographic progression. We certainly need to keep that in mind. We also must look at comorbidities. We have to know what else is going on with that patient. Do they have fatty liver disease? Are they obese?

Are there fertility issues that we need to be aware of? Have they been formally diagnosed with inflammatory bowel disease? Or are we suspecting that they may have mild disease, including microscopic involvement, and they just have to date maybe symptoms such as abdominal pain, bloating, diarrhea, but have not been formally diagnosed? Then we must factor in patient preferences. Do they want an oral agent? Do they want a self-administered injection?

Do they want IV [intravenous] therapy? Do they want to come in for an IV or an injection that’s administered by a health care professional? These are all the kinds of things that we must factor in. Certainly, the frequency of administration, that may be important to the patient as well. And certainly, coverage and cost is something that we need to factor in.

We are blessed to have a lot of different treatment options available for our patients with psoriatic arthritis, and all of us have gotten good at running this algorithm in our minds when we are picking a treatment option for a patient who’s sitting with us in the room at that particular moment. There’s this continuous kind of calculation going on in our minds.

Psoriatic Arthritis Treatment Factors: Comorbidities

 The presentation by Naomi Serling-Boyd, MD, et al at the ACR Convergence [American College of Rheumatology annual meeting] was reassuring in many ways. At the beginning of the pandemic, we were all concerned that our patients with chronic autoimmune inflammatory diseases on various immunosuppressants may be at an increased risk of contracting COVID-19 [coronavirus disease 2019] and complications from the virus itself. There was an earlier report that perhaps patients with rheumatic diseases on immunosuppressant drugs were requiring mechanical ventilation more frequently than their counterparts without these diseases, without these therapies.

This was a cohort study conducted within a large health care system that comprised both academic centers and community hospitals. Patients with rheumatic diseases, mostly rheumatoid arthritis and lupus, on various therapies including corticosteroids, conventional synthetic DMARDS [disease-modifying antirheumatic drugs], biologics, and hydroxychloroquine, who had contracted COVID-19 were compared to patients who were COVID-19 positive as well, but did not have these rheumatic diseases.

The outcomes that we’re looking at were rates of hospital admission, rates of admission to the ICU [intensive care unit], requirement of mechanical ventilation, and death. And when the patients were normalized or matched for other background factors, such as age, sex, race, smoking history and other comorbidities, there was not an increased risk associated with having these rheumatic diseases and on these various therapies for those outcomes.

They were well matched, which is reassuring for us and for our patients. They also looked at and reported on the rates of requirement for mechanical ventilation in patients with rheumatic diseases who had COVID-19 early in the pandemic as opposed to later in the pandemic. The trend was similar to what we’re seeing in our clinical practices as well, that patients are requiring less mechanical ventilation, not only for the general population without these diseases, but for our patients with autoimmune diseases as well.

Data on COVID-19 in Patients With Rheumatic Disease

 John Stone, MD, PhD, presented a late-breaking abstract at the ACR Convergence [American College of Rheumatology annual meeting] on the use of interleukin-6 [IL-6] inhibition in patients with COVID-19 [coronavirus disease 2019] not on mechanical ventilation. This is important information. This was a randomized, double-blind placebo-controlled trial, a fairly large trial randomizing patients to interleukin-6 inhibition along with standard therapy versus standard therapy alone in patients hospitalized with COVID-19 who had elevated acute phase reactants.

They had to have 2 out of 3 other factors, including temperatures greater than 38 °C, pulmonary infiltrates on imaging, or the need for supplemental oxygen. These were very sick patients, and they were randomized 2:1 to receive standard therapy plus interleukin-6 inhibition versus standard therapy alone. The outcomes they were looking at were the time to ICU [intensive care unit] admission and time to a requirement of mechanical ventilation.

Those were the primary outcomes. The secondary outcomes they were looking at were the time to worsening of clinical picture as well as the time to not requiring oxygen. Basically, this was a negative study. There was no difference in terms of the risk for requiring mechanical ventilation, ICU admission, or death between these 2 groups, the ones that were receiving interleukin-6 inhibition versus those that were not. And similarly, time to improvement and time to worsening of clinical picture was the same as well.

During the course of this pandemic we’ve all been confronted with patients calling and asking about their therapies, and I think this was more true earlier in the pandemic when we knew less. It was nice to see at the ACR Convergence that there was a lot of information that supported the decisions we were making earlier on. We may have been more conservative in the beginning. And there are data to support that a lot of the treatment changes that were being made prior to the ACR coming out with their recommendations in early, mid-April, that a lot of the treatment decisions and changes in therapies were driven by patient preferences.

The patients were making changes to their therapies. After the ACR recommendations, a lot of the treatment decisions that were occurring were physician driven. That’s because we have a better foundation. In terms of what I’ve been doing with my patients, it’s been reinforced by what my colleagues have been doing and what was presented at the ACR Convergence, and that is in stable patients on therapy, we are not recommending that they stop or interrupt therapy.

It’s important for them to practice all the measures that we all need to be practicing. That includes social distancing, handwashing, the use of masks. The nice thing was that early in the pandemic we had these concerns that we might see a lot of infections in our patients or worse outcomes. That wasn’t the case, at least in my practice and from the colleagues I’ve talked to and the experiences that I’ve heard. I think part of that has to do with the fact that our patients, prior to the pandemic or during the pandemic, didn’t need a lot of convincing.

They were the first ones to buy into using masks and social distancing and handwashing. They were well aware that they had a chronic underlying autoimmune inflammatory disease and they needed to be very careful. There was a lot of concern about the continuation of medication, and we got a lot of questions in the beginning. But as things have played out, we’ve made the right treatment decisions in encouraging our patients to continue on therapy because the benefits seem to be outweighing the risks.

And certainly, our patients, based on the information that we have, are not at an increased risk of COVID-19 or complications thereof based on their disease or their therapies. Perhaps it’s the other factors and comorbidities that play a bigger role.

IL-6 Receptor Blockade in ICU Patients With COVID-19

 The availability of the ACR [American College of Rheumatology] guidelines for the treatment of our patients with rheumatic diseases during this time of COVID-19 [coronavirus disease 2019] has been very helpful. It has reinforced what a lot of us were thinking intuitively, but it’s nice to have something in print, something available on a web page, for not only us to refer to, but for our patients to see that we’re not just making things up by the seat of our pants, that there are other experts who have gotten together and come up with these guidelines.

This is a living document as they refer to it, and things evolve. Having these statements and these guidelines have helped reinforce what I was doing, and what a lot of our colleagues are doing as well. It has been reassuring to be able to tell patients that, “Look, you have a chronic autoimmune inflammatory disease, and based on the information we have, it’s important for you to continue on your therapy, and the benefits are outweighing the risks.”

I have some examples of the kind of tools I use to educate my patients about that. I break it down in layman’s terms, and they seem to understand the importance of continuing on therapy. Obviously we emphasize the importance of the measures that we really all need to be doing in terms of social distancing, handwashing, the use of the mask, hand sanitizing, and so forth.

The guidance also expands on what do you do when your patients have known exposure. They don’t have symptoms necessarily. They don’t have COVID-19, or at least we don’t know, but they’ve had exposure. That’s been nice to refer to as well.

Treatment Modification: ACR COVID-19 Guidelines

 The most common reason for referral to us of a patient with psoriatic arthritis is from a dermatologist who has been seeing the patient for their psoriasis and has picked up that the patient has pain or swelling in a joint, swelling in a whole digit, or other pain complaints. For whatever reason, the dermatologist has asked the patient about it because they know the importance of screening for psoriatic arthritis or because the patient has just brought it up and said, “Hey, Doc, what do you think about this swollen digit?”

When we see the patient, 1 of the interesting things is that they will often remember that their symptoms have gone back for some time, and sometimes it’s enthesitis but not arthritis that the patient remembers. For example, a difficult Achilles tendon pain problem, plantar fascia, or even chest pain because of the enthesitis in the rib cage. Enthesitis and arthritis bring the patient to our attention. A more difficult area for us to evaluate is back pain. The patient may either have back pain at the initial presentation of psoriatic arthritis or develop it later on. Sorting it out from a degenerative arthritis is often difficult.

All these things are what bring the patient to us, but if we dive further we find other symptoms. Fatigue is a very prominent issue, and sometimes the comorbidities are obesity, hypertension, or hyperlipidemia. For those we have to get on the patient to make sure they’re attending to them with their primary care physicians.

These are the ways in which we see these patients, and they typically have multiple clinical domainsoccurring. I’ve already alluded to several, in addition to skin and nail disease, and all of them significantly impact them in terms of function and quality of life.

Of course, history and a physical are how we make the diagnosis. One of the interesting things to support that point is that in the PREPARE study that we published in 2013, where in nearly a 1000 patients attending psoriasis clinics were seen by a rheumatologist, and 30% were noted to have psoriatic arthritis. It turned out that just doing the history and physical could, essentially, correctly diagnose virtually every patient. We were allowed to do additional lab and imaging, but it was only rarely that we would need to have that in addition. So the history and physical are key.

The nature of joint pain: Is there stiffness involved? Is the joint pain persistent and not evanescent? The distribution of joints that are involved: Is there evidence of enthesitis at the heel or around the knee? Is there evidence of back pain? Does the patient have evidence on exam of swelling in their joints or swelling of a whole digit characteristic of dactylitis? Do they have evidence of nail disease, which was 1 of the common coexisting cutaneous aspects with psoriatic arthritis? This really helps establish it.

In terms of laboratory, unfortunately there is no biomarker, like rheumatoid factor or CCP, that can help us make the diagnosis. In only 30% to 40% of patients, even with active psoriatic arthritis, was their acute phase reactant of SED [sedimentation rate] rate or C-reactive protein elevated. If they’re elevated and we see them change with treatment, then this can be a useful biomarker. But in many patients, this is not present. Imaging can be helpful, especially in our clinic. Advanced imaging with ultrasound looks for evidence of synovitis, for example, or enthesitis using gray scale. Power Doppler can be very helpful in making the diagnosis and contrasting the disease with osteoarthritis or even gout, which can be in the differential diagnosis, as well as rheumatoid arthritis or spondylarthritis.

The CASPAR [Classification Criteria for Psoriatic Arthritis] criteria is a classification system. It’s not intended to be diagnostic, although some clinicians will use it in that way, including dermatologists. The CASPAR criteria were published in 2006. It was a 4- or 5-year effort. Our center [Swedish Medical Center in Seattle, Washington] was 1 of the participating centers, and it came up with the following elements. If a patient has, in your opinion, synovitis or arthritis that is inflammatory in nature or enthesitis or spondylitis that is inflammatory in nature, then that’s the stem of the criteria. If this is met, then you can apply the rest of the criteria. If the patient currently has psoriasis, that gives them 2 points toward the necessary 3 to be classified as PsA [psoriatic arthritis]. If they have a negative rheumatoid factor, that gives them another point. Although we found in the CASPAR study that about 5% of PsA patients had rheumatoid factor positivity, so its positivity does not rule it out. If they have some nail changes or a few other features that will give them the points. The most common way of classifying them is with current psoriasis and a negative rheumatoid factor, and that gives a specificity of 99% and sensitivity of 93%, which is very good for classification criteria. In this way we classify patients to bring them into trials, but these are also useful questions to ask and examine patients as we’re looking for evidence of psoriatic arthritis.

Accurately Diagnosing Psoriatic Arthritis

 There were 2 phase 3 trials, known as DISCOVER-1 and DISCOVER-2 that led to the approval of guselkumab in the treatment of psoriatic arthritis, which is relatively recent. In DISCOVER-1, which was a smaller trial, about 30% of the patients had been treated with TNF [tumor necrosis factor] agents previously and 70% were bio-naïve. In that study, the ACR20 response at 24 weeks—the primary end point—was highly statistically significant compared with placebo. Two dose arms of guselkumab were studied, giving it every 8 weeks, which is the same as the psoriasis dosing, or giving it every 4 weeks. As it turns out, the approval is for every 8 weeks, and the data with that showed an ACR20 response of 52%. The skin scores were very high, with 76% of patients achieving a PASI 75 [Psoriasis Area and Severity Index decrease of 75%], for example, and in the psoriasis trials those numbers are even higher. Guselkumab is turning out to be, like the other IL-23s, 1 of the best agents we have in treating the psoriasis component. There was also very meaningful resolution of enthesitis and dactylitis with guselkumab in this trial.

In DISCOVER-2, this was a completely bio-naïve population. Here we saw two-thirds of patients achieving an ACR20 response at week 24 and high rates of resolution of enthesitis and dactylitis, very high skin responses, and improvement in patient-reported outcomes, such as function, pain, and fatigue. Interestingly, this trial was 1 of the first that led to the FDA allowing in the claim or in the label for guselkumab to say that it can benefit fatigue. We know that that’s a very important issue for our psoriatic arthritis patients, and so this is actual recognition of them.

In that trial, the every-4-week dose was able to show statistically significant ability to inhibit structural damage progression by x-ray. The every-8-week dose just barely missed that. It looks like the drug is able to benefit, but it could be a dose issue. Safety profile was very good, with very low rates of serious infection. There was no signal for things like cancer, cardiovascular events, herpes zoster, malignancy, or inflammatory bowel disease, so a very reassuring safety profile was achieved.

In the more recent meeting, we saw a very interesting study with guselkumab in which the spondylitis aspect of PsA [psoriatic arthritis] was explored. I use the word 

 because it wasn’t a definitive study with MRI scans and so forth, but it was an effort to see whether the drug would benefit the symptoms of spine disease. The reason this is an interesting question is because historically we’ve seen 1 agent, a similar P19/IL-23 inhibitor, have a trial in ankylosing spondylitis and not show benefit compared with placebo. We’ve also seen the same with ustekinumab, which is an IL-12 and IL-23 inhibitor. There was some question about whether the drug would work in the spine. In this subset analysis, patients who had clearly abnormal, sacroiliac joints on x-ray and had elevated spine pain scores—and were considered by the investigator to have axial PsA [psoriatic arthritis]—were included. We saw with both dose arms of guselkumab clear improvement of spine-related symptoms in the form of improvement of BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], the spine pain question, the ASDAS [Ankylosing Spondylitis Disease Activity Score]. So it gives us some window into the idea that maybe the IL-12/IL-23 inhibitor is working in axial PsA [psoriatic arthritis], even though another agent didn’t seem to work in ankylosing spondylitis. We know that there are enough differences between axial PsA [psoriatic arthritis] and ankylosing spondylitis that maybe there is some immunobiologic reason why this would be the case. This is going to be further explored. Again, I consider this data exploratory, and we’ll see more learning about whether IL-23s worked well in axial PsA in the future.

Guselkumab for Psoriatic Arthritis

 These were very interesting data. Deucravacitinib is an oral medication. It is a selective tyrosine kinase 2 inhibitor, a TYK2 inhibitor. So in the Janus kinase family there is JAK1, JAK2, JAK3, and TYK2, so all these are considered part of the Janus kinase family. They have a role in facilitating signaling from a receptor on, say, an immune cell surface for a potentially pro-inflammatory cytokine, which then signals into the cell and gets the cell to turn on and produce more inflammatory cytokines. Giving an inhibitor to 1 of these JAK molecules inhibits this signaling. There are many pro-inflammatory cytokines that signal through this mechanism. And whether it’s a JAK1 and JAK3 or a JAK1 and TYK2 at the receptor site makes a difference in which cytokines are doing the signaling. For example, if they are, TYK2 we know has a role in inhibiting signaling by interleukin-23. From the data that we just discussed with guselkumab, we know this a very important cytokine in the pathogenesis of psoriasis and psoriatic arthritis. There are other cytokines that are affected as well.

This particular molecule, deucravacitinib, is also unique in that it is an allosteric inhibitor that attaches to the regulatory domain instead of the ATP-binding active side of the catalytic domain. It is extremely specific for TYK2 in that way, and this ultimately may have some impact on efficacy or safety.

This was a phase 2 trial, and the results were good. We saw at ACR20 [American College of Rheumatology 20% improvement] that the response at week 16 with the 6-mg dose was 53%; with the 12-mg dose, it was 63%. We also saw over time that there was a quick onset of action upon reaching these particular end points. We saw a statistical separation between the treated groups and placebo with ACR50 response or ACR70 response, and we also saw significant improvement in function, SF-36 [Short Form 36 health survey] physical component, the Leeds Enthesitis Index, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, and the achievement of minimal disease activity goal in about 23%, 24% of the patients, depending upon the dose arm.

Of course, we anticipated that we would see a good skin response because of this particular mechanism of TYK2 inhibition. We’ve seen a separate psoriasis phase 2 study, in which 69% of patients had achieved a PASI 75 [Psoriasis Area and Severity Index decrease of 75%], response. This is a little higher than what we’ve seen with the other JAK inhibitors, and it’s consistent with this mechanism. We saw good rates of skin improvement in this trial, and this is exciting. Oral is a new mechanism; the safety profile was very good in both this trial and the psoriasis trial. We really haven’t seen much in the way of signal of major problems, so we’re very much looking forward to this moving forward into a phase 3 study.

Deucravacitinib for Active Psoriatic Arthritis

 The EQUATOR-2 trial was a study of filgotinib, which is a relatively JAK1-specific JAK inhibitor, in patients with psoriatic arthritis. That study has been reported out previously and was published in 

. It showed high rates of response in terms of ACR [American College of Rheumatology] scores on enthesitis and dactylitis and improvement of physical function, all the things we want to see in the psoriatic arthritis trial. This was a study looking more specifically at the end point of enthesitis. What we saw was that by the end of the original study, at week 16, we had seen resolution of enthesitis in 52% of patients, compared with 26% on placebo, using an end point known as the Leeds Enthesitis Index. We also saw 35% of patients on filgotinib vs 23% on placebo using a Canadian enthesitis measure called the SPARCC [Spondyloarthritis Research Consortium of Canada] score.

As we tracked patients out to week 52, two-thirds of patients achieved complete resolution of enthesitis using both scoring methodologies. What does this tell us? Because it took a little bit longer than the 16-week mark to achieve the full benefit, the enthesitis domain is a little tougher to treat. It’s less vascular. There is more biomechanical pressure and microinjury going on. So it’s not that unusual to see only the partial benefit, in this case, of about half the patients achieving full resolution. That is good at week 16, but we have even better results as we go out over time. It’s telling us to be patient in your patient who’s in front of you who has, say, a troublesome Achilles tendon insertion site that’s providing problems with work or exercise. Whether it’s with this drug or with other drugs, we’ve seen this longer time to complete resolution.

Treating Enthesitis in Psoriatic Arthritis Patients: Filgotinib

 These data are from the SELECT-PsA 1 and 2 trials using a drug known as upadacitinib, a relatively specific JAK1 inhibitor, in the treatment of psoriatic arthritis. In the SELECT-PsA 1, which was a larger trial involving bio-naïve patients and the primary end point, the ACR20 [American College of Rheumatology 20% improvement] response was seen in 71% of patients on the 15-mg dose of upadacitinib and 79% on the 30-mg dose. There was an adalimumab reference arm in which 65% of patients achieved an ACR20 response.

They’re very similar, and actually the 30 mg was superior to adalimumab, and all these were superior to placebo. These are very high rates of response, and we saw correspondingly high rates of ACR50 and ACR70 response as well. The resolution of enthesitis was 50% to 60%, and the resolution of dactylitis was 70% to 80%. These are for all the arms of the study. These are excitingly good results.

Also, in the skin we saw two-thirds of patients having a PASI 75 [Psoriasis Area and Severity Index decrease of 75%] response, which is very good. In terms of achievement of minimal disease activity, in this trial about a third of patients in the 15-mg arm and 45% in the 30-mg arm achieved this. Also, x-rays were assessed, and we saw inhibition of structural damage progression in the radiographs.

The adverse-effect profile was similar to what we’ve seen in rheumatoid arthritis. There was a bit more herpes zoster in the upadacitinib-treated patients with some dose effect, with more in the 30-mg dose, and this was true of the serious infection rate as well.

There was a single VTE, or venous thromboembolism event, in the placebo group, 1 in the upadacitinib 30-mg group, and 2 in the adalimumab 40-mg group. So it’s balanced between the different arms of the study.

A second trial, which I had the opportunity to present, was the SELECT-PsA 2 study, for patients who had had previous exposure to the biologic agents, such as TNF [tumor necrosis factor] inhibitors. In that trial we also saw good ACR responses. For example, in the 15-mg dose, 57% achieved an ACR20 with high rates of enthesitis and dactylitis resolution, good skin responses, and about a quarter patients achieving minimal disease activity criteria.

The safety profile in that trial was pretty similar to what I just mentioned, in SELECT-PsA 1. This drug is going forward with the FDA application for approval in psoriatic arthritis as well as axial spondylarthritis, so we’re excited to see additional entries into the JAK inhibitor class that we will be able to use as effective oral medications in psoriatic arthritis.

One of the things I find very exciting doing research and education in the fields of psoriatic arthritis and spondylarthritis is how much these conditions have come to the fore, with much more interesting research on pathophysiology, on clinical presentation, on how you measure the diseases. Or how we can develop biomarkers to try to identify the diseases earlier and develop measures that are targets of low disease activity or remission, which we try to achieve so we can practically use that in the clinic.

We saw a number of abstracts in all these areas, so I’m really proud that there are so many rheumatologists around the world who have a real interest in these diseases and are seeing that these patients get treated effectively. It’s become a substantial part of our meetings, so I’m happy to see them.

Optimal Management of Rheumatic Disease During COVID-19