‘Set the target, assess, adjust’: Drug choice for RA, PsA hinge on safety, efficacy, risks
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DESTIN, Fla. — Efficacy is just one of many factors that should be considered when choosing therapies for rheumatoid arthritis and psoriatic arthritis, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“If you are not on target, you have to make choices,” Daniel Aletaha, MD, of the division of rheumatology at the Medical University of Vienna, in Austria, told attendees. “This is what I am going to reflect on for a bit here today.”
Aletaha stressed that he had no clear answers about how to choose treatments in RA and PsA. “Context matters,” he said, noting that “drug safety gestalt, patient multimorbidity profile, cost, disease manifestation, access and anticipated efficacy” are all factors that should go into therapeutic selection.
While he acknowledged that FDA approval can inform rheumatologists that a drug is efficacious, efficacy is not the only parameter used by clinicians to make treatment decisions.
“Approval is just a bar that tells us they passed a test of efficacy,” Aletaha said. “Efficacy is a starting point. But you are looking for strategic evidence, strategic trials that tell you how to use this drug, how it will work in clinical practice and how it compares to other drugs.”
Aletaha offered the example of methotrexate in RA vs. PsA to highlight a broader interpretation of what efficacy can mean.
Conventional wisdom suggests that methotrexate is a good first choice for patients with RA but is a poor first choice for axial spondyloarthritis. “In PsA, it is a maybe,” he said. “There is no clear yes or no.”
But despite that “maybe” status, Aletaha showed that patient retention rates for MTX are “almost identical” in RA and PsA, meaning that as many PsA patients as RA patients who begin using this medication will continue taking it. “Retention rates in clinical practice are almost the same as efficacy,” he said. “Retention rate is a rough, not very precise, indicator of its value. But it does show its value.”
It was in this context that Aletaha addressed the concept of “precision medicine” in rheumatology.
“There is a narrow meaning of precision medicine that people use: molecular composition used to predict drug choice or outcomes,” he said. But this does not reflect the reality of rheumatology practice. “There are currently no clinically useful baseline biomarkers that can be used in individually tailored biologic treatment in RA.”
The reality of clinical practice is that precision medicine can take many forms. “There are shades of precision,” he said. “It can be precise or not precise.”
Aletaha suggested that there are “different levels” of precision. “In real clinical practice, you do an exam and take images, and then you make a choice,” he said.
Depending on the patient’s response to that choice, more steps may be required. “You do a lab test; you do a biopsy,” he said. “With each step your treatment becomes more precise.”
If there is another critical component of precision medicine in current rheumatology practice, it is safety. “We are really looking at safety rather than efficacy,” Aletaha said. “We are matching patient comorbidity profiles with specific adverse event profiles. For example, if we have had a patient who has had a couple of herpes zoster episodes, we do not think about which drug is more efficacious, we think about which drug is less likely to cause zoster reactivation.”
Returning to the topic of regulatory approval, Aletaha suggested that it is for all of these reasons that both the American College of Rheumatology and EULAR are “very vague when it comes to telling you which drug to choose” in RA and PsA. “Every individual is different,” he said. “We need to balance the risk of disease with risk of therapy.”
To that point, he offered a simple plan for rheumatologists to follow: “Set the target, assess, adjust,” he said.
As a final point, Aletaha highlighted the importance of shared decision-making. “If patients are not with you, any drug will not work,” he said.
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Aletaha D. How to make the right treatment choice in arthritis: efficacy, safety, context, and preference. Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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