“Many hurdles” stand in the way of precision medicine for rheumatoid arthritis


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Cohen S. Advances in treating rheumatoid arthritis with precision medicine – how close are we? Presented at Biotherapeutic Summit X. May 11-13, 2023 (hybrid meeting).

Disclosure:
Cohen is reportedly consulting or investigating Amgen, Abbey, Boehringer Ingelheim, CoHealth, Merck, Pfizer and Sandoz.


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According to Biotherapeutic Summit presenters, the slow progress towards precision medicine in rheumatoid arthritis is characterized by increased use of serum biomarkers and new approaches to biopsy, but there are “a mountain of hurdles. ” remains.

“We have been working hard for years to advance rheumatoid arthritis treatments towards more precision medicine.” Dr. Stanley Cohen, He, a clinical professor of internal medicine at the University of Texas Southwestern Medical School and co-director of medicine at the Metroplex Clinical Research Center, told attendees.

Images of hands with arthritis

“Precision medicine in rheumatoid arthritis faces many hurdles, but we are making progress.” Stanley Cohen, medical doctor, said to the attendees. Image: Adobe Stock

He said the conventional wisdom of a decade ago was that much of the pathogenesis of rheumatoid arthritis occurred through the TNF and interleukin-6 pathways, and drug therapy targeting these pathways was the most likely to be successful. suggested that it was

Stanley Cohen

But genomics, proteomics, transcriptomics and metabolomics, which Cohen called the “age of omics,” have brought the field closer to a more specialized therapeutic paradigm.

Rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or four shared epitope-positive domains may be pushing rheumatoid arthritis treatment toward precision medicine, Cohen said. Role of the synovial membrane in treatment selection. prime cell. and liquid biopsy.

Regarding seropositivity, Cohen noted that analysis of rituximab (Rituxan, Genentech) showed that both RF and ACPA positivity correlated with greater treatment response.

“But Rituxan in rheumatoid arthritis is commonly used as a salvage therapy,” he says.

Seropositive patients have a greater response to the drug than seronegative patients.

Similarly, in a post hoc analysis of trials comparing abatacept (Orencia, Bristol Myers Squibb) with adalimumab (Humira, Abbvie), results showed that higher ACPA titers improved responses to abatacept. But Cohen didn’t like to draw firm conclusions.

“Perhaps abatacept may respond somewhat better in ACPA-positive patients,” he said.

Similar conclusions were reached with the results of the AMPLE study.

“Here, there appeared to be a signal that high titers of ACPA or shared epitope positivity might enhance responsiveness to abatacept,” Cohen said.

He added that more research is needed to better explain the relationship between biomarkers and treatment.

Turning to the synovium, Cohen discusses how rheumatoid arthritis histologic subtypes, including lymphoid/myeloid, diffuse myeloid, and myomatous intestinal immunity, may be clinically useful. discussed.

“Patients with lymphoid/myeloid systems are more likely to have rheumatoid arthritis than nonspecific arthritis,” he said. “For the first time, information from the synovium may provide information about what happens to patients from a prognostic perspective.”

Although data on this are not yet ready for “golden time,” Cohen expressed hope that the synovial membrane could help bring the treatment of rheumatoid arthritis to precision medicine.

“Synovial gene expression may help us understand which patients need to receive more aggressive treatment,” he said.

Up to that point, an R4RA study comparing rituximab with tocilizumab (Actemra, Genentech) showed that patients with diffuse myeloid signatures responded better to tocilizumab by RNA sequencing and synovial gene expression. was shown.

According to Cohen, if there’s one approach to precision medicine for rheumatoid arthritis that’s far into the future, it’s prime cells.he focused on data from Dana Orange, M.D., M.S., This indicated that PRIME cells are activated by B cells in the blood just before RA relapses.

“I don’t know what to do with this data, but it’s interesting,” Cohen said.

Liquid biopsy, on the other hand, is a precision medicine approach and could be used because synovial biopsies are difficult to perform, he added.

“We’re not good at synovial biopsies,” Cohen said. “It’s hard to get tissues.”

Liquid biopsies are blood-based and therefore less invasive.

Cohen emphasized that the PRISM RA tool as a predictor of non-response to TNF inhibitors is a potentially minimally invasive way to guide clinical decision-making. However, although the data show a high positive predictive value, there are varying levels of sensitivity and specificity associated with this product.

“There are many hurdles to precision medicine in RA, but we are making progress,” Cohen said, before, in the words of Winston Churchill, “we are at the end of the beginning.”



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