‘Devil is in the details’ for choosing relevant targets, endpoints in RA, PsA
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DESTIN, Fla. — Making sense of the myriad targets for the myriad disease domains in rheumatoid arthritis and psoriatic arthritis presents ongoing challenges for every rheumatologist, a presenter said here.
“Remission is a term we use a lot, but it needs to have a meaning,” Daniel Aletaha, MD, of the division of rheumatology at the Medical University of Vienna, in Austria, told attendees at the 2023 Congress of Clinical Rheumatology-East. “That is what I am going to elaborate on a bit.”
While most rheumatologists would agree that they would aim to get every patient into remission, Aletaha acknowledged the complex challenges associated with reaching this goal in RA and PsA. “The devil is in the details.”
The discussion raised the pros and cons of several outcome measures in both diseases.
Regarding the DAS28, Aletaha suggested that patients may fulfill this criteria but can still have one, or two or as many as 12 swollen joints. In addition, in clinical trials, approximately 30% of patients can meet DAS28 criteria and still have multiple swollen joints.
The reason DAS28 continues to be used in clinical trials is because it is not as “stringent” as other measures, including the Boolean criteria for remission. “If you are going to do a study that targets remission as an outcome, it is pragmatic to use DAS28,” Aletaha said. “But people hear remission and think of patients who are doing fine; they do not consider that these patients may have residual disease activity.”
Aletaha does not want to discourage researchers from continuing to study DAS28, but he offered his own pragmatic point. “Sure, use it,” he said. “But don’t call it remission.”
While the Boolean criteria, due to its stringency, may be a stronger measure of remission, Aletaha noted that this metric also comes with disadvantages.
The main issue is that many patients will meet endpoints for three of the four criteria — tender and swollen joint count, along with C-reactive protein — but fail to meet the criteria for Patient Global Assessment (PGA).
“Pain score is causing patients to miss remission in the Boolean criteria,” Aletaha said.
He noted that multimorbidities ranging from depression to fibromyalgia are the sources of pain in many patients, causing them to miss the Boolean endpoint.
In response to this issue, the Boolean criteria were updated in 2022 to make the PGA slightly less stringent while still reflecting the pain that so many patients feel.
Digging into the details, Aletaha encouraged rheumatologists to differentiate between pain associated with RA and pain associated with other comorbidities that patients may be experiencing. “The distinction between RA-related pain and unrelated pain is notoriously difficult,” he said.
The last metric Aletaha addressed in RA was low disease activity. “Everyone in clinical practice would say it is impossible to get every patient into remission,” he said. “If you have a long-standing patient who is doing well, it might be acceptable to go for LDA.”
While Aletaha acknowledged that LDA is also poorly defined, he suggested that if a patient is responding well to a TNF inhibitor or an interleukin-targeted therapy, this could be sufficient intervention. “If the patient is happy with LDA, you can possibly be happy, too.”
Because psoriatic disease is so much more complicated and involves so many more clinical domains, Aletaha suggested that making sense of the possible endpoints and targets can be overwhelming. He noted the Psoriasis Area and Severity Index (PASI), body-surface area (BSA) for skin, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Disease Activity Index in PsA (DAPSA) and Clinical Disease Activity Index (CDAI) as measures that each come with their own pros and cons. A Boolean metric can also be used in PsA, along with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) algorithm.
Aletaha suggested two potential courses of action for sorting out all these endpoints. The first is a “unidimensional approach,” where the rheumatologist treats each domain separately. The argument in favor is that it is clear which domain is responsible for failing the target. The argument against is that there are “multiple potential targets” at any given time.
Conversely, there is the “multidimensional approach,” where all the domains are combined into a single target. This single target is the key “pro” for this approach. However, the “con” is that all domains need to be formally assessed every time, according to Aletaha. “All have different treatment algorithms,” he said.
“Psoriatic disease is really complex,” Aletaha added. “The same way we treat complex patients, we have to treat complex disease.”
As a final point, Aletaha urged attendees to consider the time and effort required to help any given patient achieve any of these endpoints. “We have to balance what we are hoping to achieve with the costs, risks, side effects and resources in our medical practice.”
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Aletaha D. What is the right target in RA and PsA? Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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