Synovial imaging, biopsy fall short of 'the promised land' to guide RA therapy
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Advanced imaging and biopsy of the synovium have not led clinicians to “the promised land” in terms of guiding treatment for rheumatoid arthritis, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
William F.C. Rigby, MD, professor of medicine, microbiology & immunology at the Geisel School of Medicine at Dartmouth-Hitchcock Medical Center, discussed three main topics in his talk: One was the utility of imaging to predict transition to RA; the second was drug tapering; and the third was investigating the future role of synovial biopsy in predicting response in RA therapeutics.
It was clear that there are more questions than answers to these questions. Rigby discussed how the “seductive model” of RA pathogenesis is that anti-citrullinated protein antibodies (ACPA) form as mucosal IgA, progress to systemic IgG1 and, eventually, to synovitis over the course of months. “But the answer is not that easy,” he said. “Often, we are talking about years or even decades.”
Rigby then took a closer look at a number of data sets from ACR Convergence 2020 that highlight his three topics.
In terms of imaging, he cited data from Rogier and colleagues, who combined findings from three cohorts comprising more than 700 patients to determine the impact of ACPA positivity and synovitis as parameters for progression to RA.
Results showed that “ACPA positivity was kind of all over the map,” according to Rigby. He added that the presence or absence of synovitis on imaging may not necessarily guide treatment decisions.
“When someone comes into my office with joint pain and ACPA positivity, but I can’t find anything on exam, I do not think there is a role for MRI or imaging for advancing beyond watchful waiting. When 50% of your patients are not going to progress, it is not worth imaging.”
Turning to the topic of treatment tapering, Rigby highlighted findings from Curtis and colleagues in the SEAM-RA study. Participants were undergoing methotrexate monotherapy, etanercept (Enbrel, Amgen) monotherapy or combination with the two drugs.
“Once you get into remission, you really need etanercept, but you do not need methotrexate,” he said. “Etanercept has the unique property to not induce anti-drug antibodies. This study established the key role of etanercept in maintaining remission.”
The implications of this on the field are important, according to Rigby. “We can transition away from the requirement of methotrexate as an anchor drug for patients for the rest of their lives,” he said.
The ARCTIC-REWIND open-label study also investigated the question of tapering, with patients in remission for >12 months on stable TNF inhibition assigned to continued stable TNF inhibition or tapering to a half dose. Patients were also treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
Results showed that 5% of patients in the stable TNF arm experienced flare at 1 year, compared with 63% in the TNF taper arm. As to whether a csDMARD can maintain remission, Rigby offered a simple response. “The answer is no,” he said.
As for the question of synovial biopsy, Rigby discussed findings from Rivellese and colleagues that included 164 patients with an inadequate response to a TNF inhibitor who underwent synovial biopsy prior to treatment with rituximab (Rituxan, Genentech) or tocilizumab (Actemra, Janssen).
“In a TNF inadequate responder population, synovial pathology was not predictive of interleukin (IL)-6 or B cell-dependent underpinnings to synovitis,” Rigby said. “The synovium has not led us to the promised land in terms of treatment response.”
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Rigby W. RA. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 5-6, 2021. (virtual meeting).
Curtis JR. Abstract 0939. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
Lillegraven S. Abstract 2010. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
Rivellese F. Abstract 2005. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
Rogier C. Abstract 481. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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