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The impact of psoriatic arthritis on patients’ quality of life and importance of an early, accurate diagnosis.

Expert Perspective on the Management of Psoriatic Arthritis

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Continued unmet needs in ankylosing spondylitis (AS) treatment, both pharmacologic and nonpharmacologic, were suggested by high levels of fatigue and pain in patients with AS receiving tumor necrosis factor inhibitors (TNFis), according to a study published in 

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“Managing pain is an important treatment goal in patients with AS, however, pain is often underestimated by clinical disease activity scoring tools, and 20% to 30% of patients report pain despite treatment with TNFis,” investigators stated. “We observed increased levels of inflammatory markers with increasing severity of pain, indicating that patients may not have been adequately responding to therapy or were poorly adherent with their TNFis.”

The Adelphi Spondyloarthritis AS Disease Specific Programme (DSP), a large, multinational survey that identifies disease impact and disease management, collected data between 2015 and 2016 from 13 countries, including those in North America (N America), Europe (EU5), Asia Pacific (APAC), and Turkey and Middle East (T&ME).

Physicians completed forms detailing patient demographics, clinical assessments, concomitant conditions, treatment history, disease status, disease activity, inflammation, and current medication usage. Patients were then invited to complete patient-reported forms, which included Medical Outcomes Study–Short Form (36-item) Health Survey version 2 (SF-36v2), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a general health status, and Work Productivity and Activity Impairment General Health Questionnaire (WPAI). Questions focused on symptoms, disease activity, health-related quality of life (HRQoL), employment status, and current treatments.

Eligible patients were aged 18 years or older with a clinical diagnosis of AS. This study only analyzed those who were receiving TNFis for at least 3 months and had completed the BASDAI pain and fatigue domains.

A total of 705 patients were ultimately chosen for the analysis (N America, n = 253; EU5, n = 328; APAC, n = 88; T&ME, n = 36). Of these patients, 37.6% reported high BASDAI pain scores and 41.3% reported high BASDAI fatigue scores. The percentage of male patients varied from 75.5% (N America) to 100% (T&ME) and the mean age was 36.1 years (T&ME) to 45.1 (EU5).

Most patients (62.4%) reported low BASDAI pain scores, while 37.6% indicated high BASDAI pain scores. In terms of fatigue, 58.7% reported low BASDAI fatigue scores, while 41.2% had high BASDAI fatigue scores. Body mass index, symptom onset, and symptom diagnosis were similar between both patient groups.

Higher levels of pain and fatigue were associated with higher impairment scores and lower SF-36v2, visual analog scale, and 5-dimensional EuroQoL Questionnaire scores. Unsurprisingly, those with severe disease status were more likely to have higher pain and/or fatigue when compared with their low pain and/or fatigue counterparts (pain: 9.1% vs 2.3%; fatigue: 8.2% vs 2.4%). Additionally, more patients with higher physician-rated “unstable” or “deteriorating” disease status were more likely to have high pain and/or fatigue levels (pain: 14.4% vs 2.5%; fatigue: 14.1% vs 1.9%).

Approximately 29% of patients with high pain and 30% with high fatigue indicated feeling happy “little or none of the time” compared with only 12% of patients with low pain and 10.3% with low fatigue.

Flares were also higher in patients with higher BASDAI pain scores (11.4% vs 3.2%) and BASDAI fatigue levels (11% vs 2.9%) as well as reporting higher joint pain and swelling, severity and duration of morning stiffness, and discomfort.

In terms of mobility, far more patients with high pain and/or fatigue reported either “some” or “extreme” mobility or self-care issues or anxiety and depression when compared with those in the low pain and/or fatigue cohort.

Of those who provided employment information, 83.2% were employed. However, patients with higher pain and fatigue were less likely to be employed (pain: 71.6% vs 89.9%; fatigue: 74.3% vs 89.2%).

Nonsteroidal anti-inflammatory drug (NSAID) usage was higher in patients reporting high pain levels when compared with low pain levels (52.8% vs 39.3%).

The study was strengthened by the real-world data presented for patients with AS treated with TNFis globally as well as demonstrating the negative impact of pain and/or fatigue as it relates to WPAI and HRQoL. However, limitations include the study’s cross-sectional nature with its restricted selection of patients, sample sizes, and data collection, such as confining the working age to younger than 65 years. Further, diagnostic decisions may be subjective as they were based upon a physician’s rating of their patient’s disease activity. Levels of change in pain and/or fatigue could not be assessed as information was only captured at the time of data collection. Lastly, while the study was potentially limited by recall bias, this possibility was reduced by collecting data during appointments.

“Our observations indicate the importance of appropriately treating AS to minimize the impact on patients' social lives, work participation, and economic and health burdens,” investigators concluded. “Lastly, our results highlight the need to explore other therapeutic approaches including nonpharmacologic interventions for the management of AS.”

Strand V, Deodhar A, Alten R, et al. Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings. 

. 2021;27(8):e446-e455. doi:10.1097/RHU.0000000000001544

Articles

“Managing pain is an important treatment goal in patients with ankylosing spondylitis, however, pain is often underestimated by clinical disease activity scoring tools, and 20% to 30% of patients report pain despite treatment with TNFis,” investigators stated.

Fatigue and Pain Levels Remain High in Patients With Ankylosing Spondylitis 

Rheumatology Research Foundation recently presented a patient webinar entitled, “Just Diagnosed: Now What?” which featured Academy-nominated screenwriter and patient Emily Gordon with rheumatologist Stuart Kassan, MD. Kassan is a Distinguished Clinical Professor at the University of Colorado School of Medicine.

As a rheumatologist, what are some of the coping methods you can give patients who are newly diagnosed with a rheumatic disease?

The most important thing is getting good information. And good information will really be best derived from the treating doctor, but also some of the very reliable foundations that are available. So as an example, in arthritis, the American College of Rheumatology, Rheumatology Research Foundation, the Arthritis Foundation, Sjögren's Foundation, Lupus Foundation. All of those are very significant sources of information. But really the main source of every patient should be your treating physician.

How can patients advocate for themselves during this journey?

Well, again, being armed with information is key, but also asking good questions. Now, and I sort of have this as a theme in how I treat patients, you need to spend time with patients. The most important thing that can happen between a doctor and a patient is to spend quality time at the beginning of a diagnosis so that questions get answered appropriately and patients feel a little bit more comfortable as to what's going on. Information is key in this in this journey. That’s what it really is: a journey. And then also, I'm getting family involved because any of these diagnoses that people get with autoimmune disease affects families as well. And so, getting the family involved at the get go is very important.

What are some of the barriers that you found that prevent patients from advocating for themselves within the healthcare system?

I keep harkening back to the time thing, and in many clinics, time is not given to patients. And this is a stumbling block for a lot of patients, as well. But also, the other problem is getting bad information. And sometimes people will go on the internet and find various sites that don't give the true picture as to really what's going on. So that's a stumbling block as well. But again, I think getting time with your doctor is the key to really finding out what's going on and then asking good questions.

How can you encourage self-advocacy to empower your patients?

Well, doing some research. A lot of patients come in and say, “Gee, I don't really want to know anything,” because, especially when they're embarking on a new medication, they feel that if they know too much, then they'll experience those kinds of side effects. But again, ignorance is not bliss here. And so, you really want to know what's going on. Sometimes it's very difficult at the beginning of a diagnosis. As an example, when somebody gets diagnosis is diagnosed early with rheumatoid arthritis it can be pretty devastating in terms of those feelings. And sometimes people go into denial. And a lot of times it's the same kind of mechanism that people experience when they get a cancer diagnosis. You know, the stages of initially denial, anger, depression, and acceptance. And in a chronic disease, people go through those same processes as well. Trying to get over the denial piece is sometimes difficult. That's where we have to work with patients as well, in terms of trying to say, “Listen, this is really what you have and you really need to try to try to deal with this.”

Do you have any tips on how to make the most out of a patient's appointment with a rheumatologist?

I tell people to write things down because otherwise you're going to forget them. Sometimes, some doctors are sort of put off by patients when they come in with a list, but I encourage it. I think it's a good idea. The encounter of an office visit is sometimes intimidating and a lot of things that are going on in a patient's mind. Actually, they've done studies looking at what happens when a patient leaves the doctor's office and they retain maybe 50% of what was discussed. So sometimes writing it down and then trying to process it in that in that way is easier. Then you can get questions answered appropriately. And then when you leave, you don't have this feeling like, “Gee, I forgot to tell them this or that,” that kind of thing.

I can imagine it's an overwhelming experience in general. Is there anything else that you would like our audience to now?

Well, the time element is really important. You want to try to get an office visit where there's a fair amount of time allotted to you, number 1. Number 2 is I encourage patients to bring family members, especially early in their in their diagnosis, so that everybody appreciates what's going on. And 2 heads are better than 1. When you leave an office, it's better to have somebody else to sort of bounce this off of and say, “Did he tell you this or that?” and to discuss that kind of thing. Those are very important things as well to bring away from an office visit. Also, part of the time thing is you want to sort of discuss what's going on. Very often at the end of the visit, patients sort of remember other things that come up and those are important things to key into as well because, often, one of the more important things that happens at the end of the visit when a patient says “oh, by the way,” that's often the most important thing that is actually on their mind and it just didn't come to them at the get go.

Videos

Stuart Kassan, MD, discusses Rheumatology Research Foundation's recent patient webinar, "Just Diagnosed: Now What?”

Stuart Kassan, MD: Encouraging Self-Advocacy in Newly Diagnosed Patients

Rheumatology Network interviewed Philip Mease, MD, to discuss recent Phase 3 data from the DISCOVER-1 and DISCOVER-2 clinical trials, presented at the ACR, which demonstrated guselkumab inhibited radiographic progression, and improved symptoms and pain in patients with active psoriatic arthritis (PsA). Mease is Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health and Clinical Professor at the University of Washington School of Medicine.

Can you tell me a bit about the key findings of the data presented at the ACR Convergence?

What we did was we presented long-term data for both clinical radiographic and safety outcomes. Safety outcome included both 2-year data for PsA, but also 5-year data for psoriasis. The overall take home message was that benefits that were seen at the primary endpoint of the phase 3 studies at 24 Weeks was sustained over the 2-year period. And in fact, using a strict analysis of the data, including MRI analysis, we saw increasing ACR responses as well as achievement of things like minimal disease, activity threshold, and so forth. So, that was a bit intriguing. Instead of seeing what we often see as a relative plateau, have benefited at the 24-week mark and then kind of a flatline thereafter, we saw climbing results out to week 52 and even beyond. Is it real? Or is it just simply the phenomenon that patients know that they're on something and are sort of more optimistic about their patient-reported aspects of these various measures? Well, that wouldn't be so true about radiographic outcomes, for example, where we saw a sustained benefit for some of the more objective parameters. But the other concept to think about is, are we by inhibiting a molecule that's fairly upstream from interleukin-17 and tumor necrosis factor (TNF)? Are we somehow over time increasing benefit at a biological level? So that's a valuable question. It's a little tough to know the true answer from this data, but it was what we observed. The key points are that the musculoskeletal benefits were maintained, as measured by the ACR20, 50, and 70 responses over time. The enthesitis in dactylitis, complete resolution was sustained and increased over time. These are slightly more difficult-to-treat domains that do actually take a longer time. Another key finding was that there was essentially no progression in the in the overall population in terms of progression of structural damage as measured by X-ray changes. This was most clearly seen in the patients that were responding well. There was an analysis breaking it down by those that were ACR20, 50, 70, or minimal disease activity (MDA) responders or not. And clearly, the patients that were clinically responding had better radiographic outcomes as well. From a safety perspective, we didn't see increasing infections and there was a relatively low serious infection rate. That was pretty consistent over time; it did not increase. We didn't see new issues arising. We didn’t see venous thromboembolism or arterial thromboembolism, which has become kind of a hot topic because of that issue being seen with some other mechanisms or other drug classes. We didn't see any flare or issues with inflammatory bowel disease, ulcerative colitis, or Crohn's disease, and we didn't see a signal related to major adverse cardiovascular events or infection. We didn't see a signal related to herpes zoster. And we didn't see issues related to any abnormal laboratory parameters. So, from a long-term safety and safety monitoring point of view, the longer that we observe the data, 5 years in psoriasis and 2 years now with psoriatic arthritis, it gives us some reassurance that we don't have to, for example, start monitoring laboratory data or turning to the patient and saying there's increasing infection or increasing worries about this or that. It remains a very stable safety pattern over time. All of this is reassuring and allows us to use the drug with fairly good confidence as we're talking to patients about it.

Can you expand upon improvements in physical function joint manifestation and skin clearance?

As I mentioned earlier, what I alluded to is the fact that although there was substantial benefit seen through Week 24, for example, roughly two thirds of the patients had achieved ACR20 response at that point in time. As we track patients over time through Week 100, for example, we saw that result climbing up to nearly 75% of patients achieving ACR20 response, we saw over 50% of patients achieving ACR50, and about a third of patients achieving ACR70 response. So, all of these are climbing or increasing responses over time. We also saw that complete skin clearance was achieved by nearly two thirds of patients, enthesitis clearance was achieved by nearly 70% of patients, and dactylitis by roughly 80% of patients. So complete clearance of skin enthesitis and dactylitis. These are very high rates and, as I mentioned earlier, an intriguing finding to see it increasing over time.

You mentioned the safety and efficacy of this drug. Were you surprised by the results of this study?

Not so much surprised as reassured when we looked at the overall rates of adverse effects at Week 24 and Week 52. As I mentioned earlier, we just haven't seen any meaning signals for malignancy, which is of course a potential concern for patients, or unusual events like herpes zoster or venous thromboembolic events, which I've seen been seen with some other classes of medication. The rates of serious infection have remained low. And so, what we have seen over time was that we didn't see increases of any of these adverse effects. That implies that the drug is not having a meaningful impairment to our immune responses to, for example, infection, and are not finding any organ system problems like liver or kidney effects or cardiovascular effects. This remains very reassuring data.

What do these results mean for both physicians as well as patients with psoriatic arthritis?

it's very important for physicians to have additional weapons in the armamentarium to treat the disease because what we find is that with most medications, biologics or oral synthetic medications, is that patients tend to have a wearing away of effectiveness over time, for a variety of reasons. Either they develop side effects from medications, or they develop drug antibodies against the medicine they're using, or the immune system just simply works its way around the treatment that is being used. So, it's important to have additional effective medications that are that are part of our therapeutic choices. This is very much that type of medication. It's effective. It appears in the various clinical domains of psoriatic arthritis and has, as we've been discussing today, sustained benefits. It can be both highly efficacious and durable. That's important for patients because they're seeking to get to a state of remission or low disease activity where they're not having to think about the disease as much in their life. The drug is given infrequently, just once every 2 months, so they don't have to be constantly reminded about the fact that they're on a medication by taking a daily oral medication or a weekly or every other week injection. And to clinicians, I think it's good for them to be able to offer a patient something that can be effective as well as relatively safe.

Does your team plan on doing any further research on this topic?

Yes. It's not just my team, but it's the global group of rheumatologists that will be enjoined by Janssen to participate in a number of different upcoming trials. For example, there is an upcoming trial studying patients who investigators consider to have what is called axial psoriatic arthritis, so they have psoriatic arthritis, but they also prominently have as part of their disease, spine inflammation and pain. And the entry criteria will include patients who have demonstrable or objective inflammation, as evidenced by MRI scans of sacroiliac joints or the spine. And we'll have a more deep and granular look to see about the effectiveness of guselkumab in this particular population in this particular domain. Another trial that will be underway is a large trial in which the every 4-week and the every 8-week dosing will be tested to look at radiographic outcomes and we’ll have sought more deep, enriched data on the ability of the drug to inhibit structural damage progression as well as show long term efficacy and safety. So those are examples of Janssen’s commitment to continuing to understand better the overall effectiveness and safety profile in patients with various aspects of psoriatic arthritis.

Philip Mease, MD, explains the recent Phase 3 data from the DISCOVER-1 and DISCOVER-2 clinical trials which demonstrated guselkumab inhibited radiographic progression, and improved symptoms and pain in patients with active psoriatic arthritis (PsA).

Philip Mease, MD: Guselkumab Achieves Long-term Improvements in Psoriatic Arthritis Symptoms

Rheumatology Network interviewed Louis Bessette, MD, MSc, to discuss his ACR presentation, “Impact of Early Pain Improvement on Patient-reported Outcomes in Patients with Psoriatic Arthritis: Results from a Phase 3 Trial.” Bessette is affiliated with the Center for Osteoporosis and Rheumatology of Quebec. He explains why pain is a largely unmet need in this patient population, the study design, and further research his team plans on tackling in the future.

What first inspired you to evaluate if clinically meaningful improvements in pain is associated with greater improvements in other prs.

As a rheumatologist, most patients come into the clinic because they have pain and pain has a major impact on quality of life. And the main reason why patients come to treatment is to improve their pain and functions. So, I think pain is related to many aspects of patient lives. It's very important to understand how can we manage pain, how can we improve pain, how can we maintain pain improvement over time, and what is the impact of managing pain over time as well as the impact on quality of life of our patients.

Why is pain a largely unmet need, particularly in patients with inadequate response to non-biologic disease-modifying antirheumatic drugs (DMARDs)?

I think there's 2 different aspects of pain and pain still an unmet need. I think as rheumatologists we’re able to control disease activity or inflammation, but there are a lot of patients complaining of pain, not always related to their disease activity, but musculoskeletal conditions. Sometimes original pain is also related to inflammatory activity in patients that we're not able to control. And we need better medication to control pain over time and also to control information. Maybe some medications have better impact on residual pain than others. So, I think there's a lot of research going on how to manage pain in our patients and what can we use that to improve pain management.

What we show is that there was a significantly greater proportion of patients who had a meaningful improvement with upadacitinib, both 15 and 30 milligrams. The other group also improved compared to placebo. However, we also found that compared to our daily demand, there were a significantly greater proportion of patients achieving meaningful pain improvement with upadacitinib 15 milligram and that differences started at 20 weeks. And in the 30 milligrams route, the differences started at 4 weeks. We know that 30 milligrams are indicated in clinics that 15 milligrams is used to treat a psoriatic arthritis (PsA). So that was the first finding. The second finding is that for those which achieve this meaningful pain improvement, as I described before, in that group compared to the group who did not met this criteria for meaningful pain improvement at 4 and 24 weeks, they also obtain that meaningful improvement at a better quality of life, higher score or the EuroQoL-5 Dimension (EQ-5D), better improvement in their function as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), better quality of life as measured by 36-Item Short-Form Health Survey (SF-36), and better improvement in work capacity and activity impairment.

What do you believe is the clinical significance of these results?

I think clinical significance is that a lot of patients obtain meaningful pain improvement and are able to maintain that for 24 weeks if they're still on treatment. And the other aspect is relating pain improvement to quality of life. So when you can achieve what we call in our study meaningful pain improvement, these patients have better function and have better quality of life. So, I think pain, as I mentioned before, is really related to many aspects of quality of life of patients. And you know, patient come into our office complaining of pain, not because of swollen joints. Pain improvement is a major, major driver of all the other aspects of quality of life in our patients.

Louis Bessette, MD, MSc, explains the impact of early pain improvement on patient-reported outcomes in patients with psoriatic arthritis.

Louis Bessette, MD, MSc: Pain Improvement and Patient-Reported Outcomes in Patients with Psoriatic Arthritis

Rheumatology Network interviewed Benjamin Terrier, MD, PhD, to discuss his study and ACR presentation, “Rituximab versus Conventional Therapeutic Strategy for Remission Induction in Eosinophilic Granulomatosis with Polyangiitis: A Double-blind, Randomized, Controlled Trial.” Terrier is a Professor of Internal Medicine at Cochin Hospital in France.

Can you give me a bit of background on eosinophilic granulomatosis with polyangiitis (EGPA) and what inspired your team to study the efficacy of rituximab for treating this condition?

EGPA is a systemic disease belonging to the family of anca associated vasculitis. So, it's inflammation of the vessel walls that are associated with antibodies against the neutrophils type of white blood cells that we named anca. And so far, there was almost no studies evaluating the treatments in EGPA, because it's a rare disease. The management was based on all the studies that evaluated the efficacy of the conventional immunosuppressive agents, mainly glucocorticoids and immunosuppressive agents like cyclophosphamide and azathioprine. In the recent French and US recommendation to manage this disease, the question of rituximab efficacy was raised mainly because in the 2 other diseases belonging to the same family, rituximab was demonstrated to be a major treatment. But the pathophysiology of EGPA is a little bit different. That's why we had to evaluate in a prospective, randomized, double-blind study the efficacy of rituximab. Some really small retrospective studies suggested that it could be an effective therapy.

What was the study design that your team developed?

We did a parallel group phase 3 study, which was the comparison of a rituximab-based regimen. So, a combination of glucocorticoids plus rituximab, compared to the conventional strategy, which is based on the severity of the disease. We have a tool, a 5 factor score, which is an a list of 5 items and if there if there isn't at least 1 of these items, the disease is considered to be severe. If there are no items, it's a non-severe disease. The conventional strategy is, in case of non-severe disease, you treat with glucocorticoids alone, and in case of severe disease, you treat with a combination of glucocorticoids plus cyclophosphamide.

The main results is, first, it was a superiority research. So we made the hypothesis that rituximab could be more effective than the conventional strategy. The first result is that it's a negative study showing that rituximab is not superior to the conventional strategy. The rate of complete remission, which was evaluated at 6 months, day 180, showed very similar results. So, it means that for the primary outcome, and for all the secondary outcome, the results were extremely similar between the 2 groups. We can consider that It's negative study. But we could also consider that maybe in some conditions, rituximab could be an alternative to cyclophosphamide, which you probably know could be really detrimental in young female, for instance, because of the toxicity on fertility. But as an epidemiological point of view, we can say that it's a similar result because it was not a non-inferiority study. We also made some subgroup analyses to identify if these results were different according to the subgroups of patients, such as the patients with anca, the patients with severe disease, and the patients with non-severe disease. The results were the same in all of the subgroups.

Not really, because the hypothesis to get a superiority of rituximab compared to the conventional strategy was a very difficult goal to achieve. And we know that the results with the conventional strategy are quite good. So, getting superiority for rituximab was possible, but not the most probabl. But I think it was very important to make the study because so far, for instance, the very recent recommendations were recommending both cyclophosphamide or rituximab, but without getting any data. And I think now, we are able to make some recommendation based on quality data, which is always important to try to find a better management for these patients.

Is there anything else that you would like our audience to know?

No, I think it's important now to evaluate new strategies, especially therapy treatments targeting the interleukin 5. And I think that this study showed that we can make some academic studies in EGPA. It was the first double-blind academic study conducted so far in the world. And I think it showed that we can make some studies in this rare disease, and I hope that we and colleagues will also conduct other studies on these diseases.

Benjamin Terrier, MD, PhD, discusses his study and ACR presentation, “Rituximab versus Conventional Therapeutic Strategy for Remission Induction in Eosinophilic Granulomatosis with Polyangiitis: A Double-blind, Randomized, Controlled Trial.”

Benjamin Terrier, MD, PhD: Rituximab for Eosinophilic Granulomatosis with Polyangiitis

Rheumatology Network interviewed Paul R. Fortin, MD, MPH, FRCPC, to discuss his ACR presentation, “COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases.” Fortin is Professor of Medicine at CHU de Quebec Universite Laval in Quebec, Canada.

What sparked your team's interest in examining the vaccine in those who are immunosuppressed and immunocompromised?

Well, that started when patients started reaching out to us when there was an announcement that there would be availability for COVID-19 vaccines in our province. The studies that have been done before we started our own project had excluded patients with systemic autoimmune rheumatic diseases, like rheumatoid arthritis or lupus, and patients were concerned that they didn't have any data they could rely on to see whether it was safe and efficacious for them. So, with that in mind, we approached our Ministry of Health and [asked] whether they would be willing to provide us with the vaccines and to allow us to study the response and the possible safety aspect of getting the vaccine in these patients.

Why do you believe B cell treatments cause reduction in immune response rates?

This is the catch 22 of immunosuppression, especially when we target the immune system. The immune problem in lupus and in rheumatoid arthritis is often related to the production of these auto antibodies, and we're targeting those producing cells, those B cells. So, by treating our autoimmune disease, we're unfortunately triggering the expected side effects that the vaccine is not going to be able to stimulate a good response. And that differs from other biologic agents where the target is not specifically the B cells. It's quite logical, when you think about the mechanism of action of these drugs, that you would have a different response. And there are several questions that could be asked now, such as the timing of the vaccination compared to timing of the treatments, especially with the cell-depleting antibodies that are given every 6 months. Maybe there could be optimization; we could not standardize the timing in our study at this point, because of the urgency of vaccinating our patients in the context of big waves in our province. The other question that we'll be asking is if you do reach a good level of antibodies, will that be sustaining at 6 months and 12 months? In fact, we're already getting a third dose as per recommendations of the public health agency here in our province and we're measuring the effect of that third dose, so we had to modify our initial protocols for that [as well].

Is there anything else you would like our audience to know before we wrap up?

One of the messages is that the question was patient-initiated. So that's very relevant. And I think it's a good place to say that advocacy can bring results in terms of modifying the public exposure and the public interest in these questions. The second thing is that both McGill University and our university here in Quebec City, Laval University, had ongoing cohorts of patients with rheumatoid arthritis and lupus that had already been followed for many years. So, it allowed us to really turn around very quickly and start a study within 2 months of asking the question when, traditionally, you would wait 2 years before you could start such a big study.

Paul R. Fortin, MD, MPH, FRCPC, discusses the impact of the COVID-19 vaccine in immunosuppressed adults and those with autoimmune diseases.

Paul R. Fortin, MD, MPH, FRCPC: COVID-19 Vaccine for Patients With Rheumatic Disease

Rheumatology Network's Top 5: November 26, 2021

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending November 26, 2021.


Rheumatology Network interviewed Ana-Maria Orbai, MD, FACR, MHS, on her study entitled, “Guselkumab-Treated Patients with Psoriatic Arthritis Achieved Clinically Meaningful Improvements in General Health Outcomes Measured with PROMIS-29 Through 52 Weeks: Results from the Phase 3 DISCOVER-1 Trial.” Orbai is Assistant Professor of Medicine in the Division of Rheumatology at the Johns Hopkins University School of Medicine, and founding director of the Psoriatic Arthritis Program.

Can you tell me a bit about the DISCOVER-1 study design and the methods your team use to determine guselkumab efficacy in patients with psoriatic arthritis?

DISCOVER-1 was a randomized control trial, comparing guselkumab with placebo. Guselkumab is a selective interleukin 23 inhibitor, which is FDA-approved for psoriasis and psoriatic arthritis based on its efficacy. In this phase 3 trial, the primary outcome is American College of Rheumatology (ACR) 20, which is quite standard for psoriatic arthritis clinical trials. But there were also psoriatic arthritis specific outcomes like the minimal disease activity, for example, in psoriatic arthritis, and health-related quality of life outcomes. And the subject of our discussion today is the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 profile, which was also collected to gain additional information on the effect of guselkumab on health-related quality of life, instead of using the traditional measures you are accustomed to, like the 36-Item Short Form Survey (SF-36) and the health assessment questionnaire disability index (HAQ-DI) physical function measure. So, it's a step forward in trying to assess efficacy with newer measures such as the PROMIS profile.

Why did you use the PROMIS-29 instruments in your analysis as opposed to other options?

PROMIS-29 is a generic health instrument. It has several advantages over older measures. And for this reason, it's easy to interpret on the PROMIS scale. A score of 50 is the general population mean. So, if someone has a score of 50 for physical function, this means that they are at the average level in the United States. So then, if we look at scores in patients with a certain disease, or we want to see the effect of a treatment, we are able to see the scores around this 50 and how they are doing relative to the population mean. And the movement with treatment is easy to interpret as opposed to just having a dry score like we are used to with the other measures. Also, because it is a generic health instrument, we can compare the health-related quality of life and the health and function of people with psoriatic disease with other rheumatic diseases with the general population. It allows some generalizability and seeing data across diseases. Another advantage is that PROMIS-29 was generated from a database of questions that are used to assess each individual domain. And these questions were generated from interviews with patients and questions were tested to make sure they didn't perform differently for reasons other than what they are intended to measure. For example, if a question is not built with these considerations, with these scientific considerations in mind, you could easily pick an item that may perform differently in men and versus women just because of how the question is phrased or because of different concepts. So, it's a source of bias if you're not asking the question properly. These questions were tested in the general population to get rid of items or questions that would perform differently in special groups, for example, by sex or by age, and only the questions that were suitable from this perspective were selected to remain in the in the database assessing each of these domains. There is also another way of administering PROMIS instruments, for example, they can be administered as a computer adaptive test, where respondents would get the first question and then, depending on their response, they will get a subsequent question with various difficulty levels so that we can get a really precise score with a PROMIS-29 profile. It's the most simple form of these PROMIS instruments. And still, it performed very well in this clinical trial. It also takes care of concerns that, for example, with a computer adaptive test, you would get different questions every time depending on the patient's response, although that's not necessarily bad. But with the PROMIS-29, all participants got exactly the same questions for questions for each of these domains every time, so it’s identical between participants and identical when they receive the questionnaire the second and the third time.

The first finding in the study was that people with psoriatic arthritis has significantly worse scores than the general population on most PROMIS-29 domains, but particularly in physical function, social participation, fatigue, sleep quality, and a bit worse for depression and anxiety. Treatment with guselkumab versus placebo led to significant improvements in these domains. The primary outcome was at 24 weeks, so there was a statistically significant effect favoring guselkumab. So guselkumab can help patients improve their health-related quality of life scores by a third and a half of a standard deviation, which are considered to be clinically significant improvements. More so, our abstract looks at 52 weeks data. These improvements last throughout 1 year, where these outcomes were measured. So, significant improvement, clinically significant improvements, and these lasted through 52 weeks through 1 year after people started treatment.

And what is the clinical significance of these results?

We already know that from the primary outcomes of the clinical trials that guselkumab improves the manifestations of psoriatic arthritis and that it does so across the spectrum of the disease, including skin, joint disease activity, arthritis enthesitis dactylitis, as well as patient-reported outcomes like pain. It is always useful to show that not only disease outcomes are improved, but that the patient's symptoms and health-related quality of life is improved. If you're making my psoriatic arthritis better, I also expect that my fatigue, physical function, and pain will improve. And this is what has now been demonstrated with a PROMIS-29 profile. I should mention that it was also demonstrated with the SF-36 and with HAQ-DI. And we see that that we can triangulate that the effect of guselkumab can also be seen with this measure with significant improvements in fatigue, physical function participation, pain, interference, and so on.

I'll tell you what this means for me for my clinic. So in in the Johns Hopkins psoriatic program, as well as in many other clinics across the United States, PROMIS-29 measures are collected not only as a part of research studies, but as well as clinical care, at least in our case. So, patients come to clinic, and they complete PROMIS questionnaires before each visit. We are not only able to see the disease activity that we measure during routine care using the joint counts, the enthesitis counts, the skin assessment, and other clinical assessments, but now we also have the patient's perspective, using the PROMIS measures. And knowing that this treatment improves the patient-reported measure as well is very useful. We also have a timeline on when we should expect some of these improvements. We know that as early as week 4, pain, physical function, and all of these outcomes start to improve and then there's buildup across as people stay on treatment longer. So I think it's helpful that patients can tell us if they improve and we can use this course to track early responses to treatment, which are always encouraging and are good motivation to stay to stay on treatment because our treatments can take longer, sometimes weeks or months, to work. It's very useful to have a measure that can tell early on that this is doing something because we're going to continue to see improvement.

Ana-Maria Orbai, MD, FACR, MHS, explains how guselkumab improved PROMIS-29 scores in patients with psoriatic arthritis. 

Ana-Maria Orbai, MD, FACR, MHS: Guselkumab Improves PROMIS-29 Scores in Patients With Psoriatic Arthritis

Soumya Chakravarty, MD, PhD, discusses the unmet patient needs in immune-mediated diseases as well as Janssen’s work in scientific innovation that allows patients to live their lives more unburdened by their disease. Chakravarty is the Sr Director and Strategic Lead in the Rheumatology Therapeutics area at Janssen.

Why do you believe fewer than 10% of patients achieved sustained clinical remission?

 The ultimate goal of all of our diseases that we have in rheumatology, such as rheumatoid arthritis or psoriatic arthritis, is trying to achieve sustained clinical remission. So being able to live without symptoms, and, as you just noted, few patients are currently, with these most common kinds of diseases, achieving that. So why is that? There are a number of factors that underpin these low numbers. First of all, this is a journey for a lot of patients living with rheumatic diseases, in terms of long treatment times, living further years with their disease before actually getting an accurate diagnosis, as well as the appropriate treatment. Secondly, there's also the issue that once the patient actually receives an accurate diagnosis, that can actually take a little bit more time before an appropriate therapy is initiated. And even with the initiation of therapy, in terms of that prescription being written, there may be additional steps with respect to the fulfillment process. This can be lengthy and complicated. There's a journey here for patients as they try to navigate this system before starting on therapy. So, at the end of the day, I think it's very important for us as Janssen to be able to understand, appreciate these factors, and then be able to move forward with addressing them. And so, our ultimate goal here at Janssen, is for those patients to be able to change sustained clinical remission. And the way to really do that is to invest in research. And our R&D pipeline reflects that in terms of our next era of treatments. But it's not only the research; it's not only having a very robust pipeline and working with our R&D colleagues, but it's also innovating and collaborating with all of the different external stakeholders that are out there, be it advocacy groups, academia, private practices, or governmental organizations to be able to ensure that all of those connections that we've talked about along the journey for these patients are being made. And that there's obviously a commitment to ensuring that patients are getting the therapy that they need at the right time. And that treatment choice and shared decision making is being implemented across the board. So hopefully, that gives a little bit of an overview of where we think, at Janssen, we're going on this question of trying to attain remission for our patients.

What are some of the unmet needs and immune mediated diseases?

There’s a tremendous amount of unmet need for patients with rheumatic diseases, despite all of the advances that we've had right in terms of all of the therapies, such as biologics, targets, synthetic disease-modifying antirheumatic drugs (DMARDs), etc, partly to delay in diagnosis and treatment. So that's just what we touched upon as one of the reasons why many of our patients are still not achieving clinical remission. And I think the challenge here is that these diseases that we encounter are chronic illnesses. These are conditions that patients have to live with, have to manage, and have to navigate this journey for many, many years. So that means it can be very debilitating. There can be a lot of challenges with respect to pain and fatigue that come with moderate-to-severe disease that the patients are suffering from. Of course, there's a disruption in quality of life a potentially increased use healthcare resources, and increased cost. And I think the other issue that we have to acknowledge and address is that patients with rheumatic diseases can wax and wane in terms of their disease course. So, not only is it a very long journey that these patients have to experience, but that they can have periods of time when their symptoms flare. That can manifest itself as swollen tender joints, more stiffness, etc. And if their disease is not effectively managed, an issue we have to all be cognizant of is that there could be these recurring painful relapses. This sums up where the unmet needs and some of the challenges remain.

Podcasts

Soumya Chakravarty, MD, PhD, discusses the unmet patient needs in immune-mediated diseases and Janssen’s role in scientific innovation that allows patients to live their lives unburdened by disease. 

Overdrive Podcast: Unmet Patient Needs in Rheumatic Disease

Rheumatology Network interviewed Mithu Maheswaranathan, MD, on his ACR presentation, “Association of Limited Health Literacy with Clinical and Patient-Reported Outcomes in Systemic Lupus Erythematosus: An Analysis from the Peer Approaches to Lupus Self-Management (PALS) Program.” Maheswaranathan is a Rheumatology Fellow at Duke University.

Can you tell me a bit about health literacy and why it's so crucial for patients with rheumatic disease?

 Health literacy is an important social determinant of health. And it's defined as the capacity for individuals to obtain, process, communicate, and understand basic health information needed to make decisions about their health. For example, adequate health literacy is needed to complete tasks like reading and comprehending prescription dosages, understanding health materials or doctor instructions, navigating the insurance and health systems, and managing medications. In rheumatology, our diseases are inherently complex, many with multi-system organ manifestations and difficult to manage medication regimens. And health literacy is crucial for patients with rheumatic disease. For instance, it can impact someone's ability to draw the correct amount of medication for subcutaneous methotrexate injection, understand the consequences of non-adherence, such as potential dialysis in uncontrolled lupus nephritis, and managing medication regimens where we're often up titrating immunosuppressants while simultaneously tapering high dose steroids at disease onset. Low health literacy is associated with worse clinical outcomes, like increased hospitalizations, higher readmission rates, greater use of emergency care, and lower medication adherence. In chronic diseases, it's an important element to address to ultimately hopefully help improve health outcomes.

What was the study design and the methods your team used to determine the association of health literacy with clinical and patient-reported outcomes?

This study used observational and cross-sectional data obtained as part of the Peer Approaches to Lupus Self-Management, or PALS, study, which was an NIH-funded randomized control trial evaluating a peer mentorship program for African American women with lupus. And the trial examined whether this peer mentoring intervention could improve disease, self-management of disease activity, and health-related quality of life in Black women with lupus. As part of enrollment into this study and ongoing follow up, participants completed various health assessments, including health literacy. We were interested to evaluate the associations with limited health literacy in this population. We used some descriptive statistics and other statistical analyses to basically compare the association of limited health literacy with these various clinical factors, including some patient-reported outcomes, and then specifically disease activity as well as damage for some of the other clinical outcomes.

We found patients with limited health literacy had worse patient-reported outcomes as well as clinical outcomes across multiple domains, including lower self-efficacy and worse patient activation, increased rates of depression and anxiety, as well as higher disease activity and lupus damage compared with those that had adequate health literacy.

We knew from some previous work that lupus patients with limited health literacy have worse patient-reported outcomes. However, this study allowed greater insight into what some of the specific factors are that are impacted by limited health literacy. We were surprised at which areas seem to be impacting our patients with limited health literacy related to disease understanding. For example, there were not statistically significant differences between the limited health literacy versus adequate health literacy group for questions on the patient activation measure (PAM) that were related to knowing what prescribed medications do and have confidence to tell their doctor their concerns. However, what was striking was on the problems related to physician patient communication reported in the patient centered care survey. In that survey, those with limited health literacy were more likely to report difficulty in getting answers to their questions that were understandable, having their physician take enough time to answer their questions, and getting as much medical information as they wanted from their physician compared to those without adequate health literacy. These results highlighted a need for rheumatologists to be better informed about ways that we communicate with our patients. Using language that they can understand and spending time to address their questions may be an important element in in terms of things that we can do to improve health literacy.

Were there any strengths or limitations of the study that you would like to highlight?

Our study did include a large cohort of Black women living with lupus and offered insight into this unique patient population with respect to health literacy, a topic that's been under-studied in lupus compared to other chronic diseases. Because various measures were obtained at baseline enrollment and followed up into the PAL study, we were able to analyze the association of many clinical factors with limited health literacy that have not yet been explored in that kind of causal pathway between health literacy and adverse health outcomes. one limitation was that the patient's all self-identified as Black race. So, we don't know whether these results would be generalizable to other groups and patient populations.

Is there anything else that you would like our audience to know before we wrap up?

I do want to thank Dr Edith Williams, who was the PI on the PAL study for the collaboration. And if anyone has any questions, feel free to reach out to me on Twitter @MithuRheum.

Mithu Maheswaranathan, MD, discusses the association of health literacy in terms of both clinical and self-reported outcomes for patients with systemic lupus erythematosus.

Mithu Maheswaranathan, MD: Impact of Health Literacy in Clinical and Patient-Reported Outcomes in SLE

Rheumatology Network interviewed Robert Terkeltaub, MD, to discuss his ACR presentation, “Phase 2 Study Results from a Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate Efficacy and Safety of Tigulixostat, a Novel Non-purine Selective Xanthine Oxidase Inhibitor, in Gout Patients with Hyperuricemia.” Terkeltaub is Professor of Medicine at the University of California, San Diego and Chief of Rheumatology at the VA Medical Center in San Diego.

What initially sparked your interest in addressing the efficacy and safety of tigulixostat in gout patients?

Well, this is a pharma-done study. I'm an advisor, as is Dr Kenneth Saag, to the program. In terms of my interest in advising, I think it's pretty clear when we treat gout patients that we could benefit from having more urate-lowering options in our toolkit. Allopurinol has a fair number of safety issues and dosing limitation issues, especially related to genetics, ethnic, and racial factors in terms of hypersensitivity, as well as issues in terms of some allopurinol resistance described in certain patient populations including Mexican Americans, and South and East Asians, who have a particularly high frequency of a gene variant that is involved in handling allopurinol oxipurinol. We also have issues in dosing allopurinol in patients with more advanced forms of chronic kidney disease. The dosing in the United States is limited compared to the worldwide dosing and so we're often stuck, as clinicians, in terms of having options for primary uric acid lowering that work in specific subsets of patients. We would benefit from other uric acid lowering options. Xanthine oxidase inhibition is the primary targeted route for lowering serum urate. I'm really enthusiastic about new xanthine oxidase inhibitor strategies where we have potent, effective, and safe agents.

Can you tell me a bit about the study design your team developed?

This was a randomized, multicenter, double-blinded, placebo-controlled phase 2 study. It took place in the United States because United States gout patients are different than gout patients outside of the country. There was also a very small active comparator group. But the primary purpose here was to explore the doses that are safe and effective and then to pursue more advanced drug development strategies.

 And what were the results of this study?

There were 3 doses of tigulixostat: 50, 100, and 200 milligrams received once daily and comparisons were relative to placebo. There really wasn't much difference between the 50 and 100 milligram dose, but the 200 milligram dose was substantially more potent. But basically, you're looking at the proportion of subjects who achieved serum urate target. The proportion of subjects who achieved a serum urate of less than 5 milligrams per deciliter was the primary endpoint. This is a more potent and effective target for limiting uric crystal deposits and promoting the resolution of uric crystal deposits. So, the fact that we were looking at a target level of less than 5 milligrams per deciliter was a significant feature of the study.

A secondary endpoint was the more conventional study endpoint of a serum urate target of less than 6 milligrams per deciliter. Typically, with allopurinol use in clinical trial settings, in terms of getting people below 6 milligrams per deciliter, you're talking about 30% to 40%. Here at Week 12 we had between 44% and 47% of people on the lower doses reaching that endpoint of less than 5 milligrams per deciliter. At 200 milligrams a day, 62.2% achieved this goal. And then when you looked at the secondary endpoint, the more conventional endpoint, and one where allopurinol will typically get somewhere between 30% and 40% of people to serum urate target, 50 and 100 milligrams per day got about 60% of people to that particular conventional serum urate target and a whopping 78.4% with 200 milligrams per day. Placebo was negligible at about 3%.

This is very potent, urate-lowering agent. The advantage of a serum urate target of less than 5 is that that's the bare minimum target that we use for people with palpable tophi, which is about 15% to 20% of patients.

Were you surprised by the results of this study?

I was pleased by the results of the study. But I mean, there was background experience that argued for this particular study design and that we would see results that look like this. Importantly, this is the first study in the United so, you really don't know until you try it in that particular population. And gout patient populations are different in Japan and Korea and China from the way they are in the United States, for example. I'm pleased to see that this drug was so effective and then that there were no particular safety signals.

Is there anything else you would like our audience to know about the study or gout before we wrap up?

This is one of a multitude of agents that are now being developed. And I think that the approaches to treating gout are going to benefit from not only monotherapies like this, but also potentially combining approaches to tackle how uric acid is handled in the kidneys and how uric acid is handled in the gut. We're improving the ways that we have of cleaning out urate in the vasculature for the most severely ill patients with gout by tuning immune suppression to recombinant urate therapy. So, it's a pretty exciting era to be working on advancing the effectiveness of care in this disease. This is an example of some of the drug development that's going on that looks very promising.

Robert Terkeltaub, MD, explains the results from a phase 2, dose-finding study to determine the safety and efficacy of tigulixostat in patients with gout. 

Robert Terkeltaub, MD: Safety and Efficacy of Tigulixostat in Gout Treatment 

Ingrid Torjesen is a UK-based freelance health journalist with more than 30 years of experience in health and medical communications. She works for numerous publications including Rheumatology Network, the BMJ and the Economist’s Intelligence Unit. Before her freelance career, her staff jobs included news editor of both Pulse and GP (the two leading UK weekly titles for primary care doctors), and opinion and features editor of the Health Service Journal (the UK’s leading health policy title). She also spent a few years working in Australia, including on Australian Doctor.

Janus kinase (JAK) inhibitors are the newest class of drugs used to treat rheumatoid arthritis. How much do you know about these drugs? Test your knowledge with this quiz.

Rheumatoid Arthritis Quiz: JAK Inhibitors

Rheumatology Network interviewed Courtney Wells, PhD, MPH, MSW, to discuss her ACR study entitled: “Impact of the COVID-19 Pandemic on the Quality of Life of Patients with Rheumatic Conditions: A Qualitative Analysis of Perceived Risk and Decision Making.” Wells is a medical advisor to CreakyJoints, an Assistant Professor at the University of Wisconsin – River Falls, sits on the Minnesota Arthritis Foundation Leadership Board, and serves as the Mental Health Director for the largest arthritis camp in the US. We discuss her initial interest in patient-reported outcomes for a generally underrepresented patient population, the study’s key findings, and strengths of her research.

What first sparked your interest in quality of life during the pandemic for generally underrepresented patients with rheumatic disease?

When we started designing this study, Kristine Carandang, PhD, and several other authors who are also working on the project, were always interested in patient perspectives. That's the work that we do; patient engagement in particular. We have several authors on this project who are patients themselves. And Kristine and I are also both patients who have rheumatic diseases. So, for us, that's square one. We start with the patient perspective and then as we watched the data that was coming out and people's experiences. We realized that there were some pretty significant disparities that were happening. We knew that those disparities exist anyway, but they were becoming clearer and clearer as the data was coming out. We decided that we were going to try to make that a focus of the paper. Certainly, that's not the whole project and we asked about a lot of other things. But that became an integral part of how we recruited for our participants, as well as the questions that we asked.

What were the key findings of your study?

The overall finding by far was that people are struggling not just emotionally during the pandemic but socially [as well]. Their rheumatic diseases were potentially being affected by the stress level that they were experiencing. For some people it was that they had a preexisting mental health condition and that was exacerbated by the stress of the pandemic and then that may be exacerbating their physical health. For other people, they had never had a mental health condition before, and they were either newly diagnosed or they were just really overwhelmed. Maybe they didn't have a mental illness, but they just felt like they were having a hard time coping and they had new symptoms that they didn't really know what they were or how to handle them. But everybody we talked to said that they were pretty overwhelmed. They were struggling to manage their mental health and that that was impacting their physical health, in most cases. Not everybody saw that, but a lot of people said that. And also, one of the things that we found really interesting was that it seemed to be that people's perception of their risk, how at risk they were for developing symptoms of COVID-19, or getting sick, or even dying from COVID impacted their ability to function, their emotions, the decisions that they made around how to cope, and what they were going to do in their day-to-day life.

Is there anything else that you would like our audience to know, before we wrap up?

The other message that we want to send out is that people were generally pretty frustrated with their healthcare. Yes, there were some providers who were great. And they transitioned fine onto telehealth and they were able to do that. But a lot of people didn't have that. They had providers who were saying [they were not] going to see patients for months at a time or people who said that they had to come into the clinic [at a time when] people didn't feel comfortable coming into the clinic. Or there were people who just felt really frustrated with our public health system and how vaccines were being allocated and that people with autoimmune and rheumatic diseases were not being prioritized. We heard a lot of information about all levels of healthcare and that people had a lot of frustrations.

Courtney Wells, PhD, MPH, MSW, discusses the impact of the pandemic on the quality of life of patients with rheumatic conditions, with an emphasis on perceived risk and decision making. 

Courtney Wells, PhD, MPH, MSW: Impact of COVID-19 on the Quality of Life of Patients with Rheumatic Disease

Rheumatology Network interviewed Robert F Spiera, MD, To discuss his ACR presentation entitled, ”Background Mycophenolate (MMF) Treatment Is Associated with Improved Outcomes in a Phase 3 Trial of Lenabasum in Diffuse Cutaneous Systemic Sclerosis (dcSSc).” Spiera is the Director of the Vasculitis and Scleroderma/Vasculitis Program at the Hospital for Special Surgery and Professor of Clinical Medicine at Weill Cornell Medical College. He explains more about mycophenolate, the study design, and the clinical significance of these results.

Can you give me a little bit of background on mycophenolate?

So mycophenolate is an immunosuppressive drug that we've been using in rheumatology for a long time and actually often using it off label. It was originally a drug that was of interest to the transplant world. But now, probably going back about 20 years, it emerged as a really important drug in the treatment of lupus nephritis. And it’s widely used in that context. In the past decade, it's been used more and more in systemic sclerosis scleroderma. Much of that experience has been based on descriptive series of retrospective experiences looking at how patients fared on mycophenolate. There's very little in the way of prospective trial experience with mycophenolate and really no double-blinded, randomized, placebo-controlled trials specifically looking at the efficacy of mycophenolate in scleroderma. Some of the organized experience we have with it, though, does come from clinical trials. So 1 trial was an interstitial lung disease trial, called scleroderma lung study, to where cyclophosphamide was compared to mycophenolate in the treatment of scleroderma-associated interstitial lung disease, with the thought being that mycophenolate is a safer alternative of cyclophosphamide. And in that double-blinded, randomized, controlled trial, patients treated with mycophenolate did as well as patients treated with cyclophosphamide. So it wasn't showing superiority, but it showed non-inferiority with what we thought was the safer medicine. The second robust clinical trial experienced with mycophenolate was in a trial that wasn't specifically designed to look at mycophenolate, but it was in the census trial that showed to be an effective therapy and preventing progression of scleroderma-associated interstitial lung disease. But in that trial, at the discretion of the investigators, patients were allowed to be on background mycophenolate or be on no background therapy, and then would get either [the medication] or placebo. And when they analyzed how patients did in the context of that trial, who were not on mycophenolate, some people were on mycophenolate and some on placebo, it was recognized that patients that had mycophenolate had less decline in their lung function than patients who were not on mycophenolate. So those were some of the background studies that led this to being a drug that's been interested in the treatment of systemic sclerosis, and actually really widely used by clinicians in many parts of the world.

 Does your team plan on doing any further research on this topic?

We have a lot of analyses to do, both of this data and other data embedded in this very robust 365-patient trial. Whether there's any further development of, lenabasum, specifically, is really unclear treatment and did not reach its primary endpoint in this trial. On the other hand, there were some benefits seen, if you did certain post hoc analyses in which for example, patients were on their background immunosuppressive therapies for more than 2 years of the point that when lenabasum was added to their therapy, there seemed to be an advantage. Patients who were on no background immunosuppressive therapy, and then received lenabasum, seemed to do better than patients on no background immunosuppressive therapy that received placebo. But I really don't know whether further development of that will happen. I think that a lot will be learned from this database about the treatment of systemic sclerosis and its various manifestations in general.

Robert F Spiera, MD, explains background mycophenolate treatment and its associated improved outcomes in patients with systemic sclerosis receiving lenabasum. 

Robert F. Spiera, MD: Mycophenolate Treatment Is Associated with Improved Outcomes in Trial of Lenabasum in Patients With Systemic Sclerosis 

Rheumatology Network's Top 5: November 19, 2021

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending November 19, 2021.
