“The ICD can mediate the pro-inflammatory effects of MIF,” Dr. Haroon says. “The antibody cannot recognize the cleaved, intracellular CD74. So, that decrease in intracellular CD74 indicates active signaling of the MIF-CD74 axis in AS patients’ monocytes.”
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Although AS patients in the progressor group tended to be smokers, smoking didn’t stand out as a factor in this analysis. NSAID use also didn’t appear to affect disease progression.
We Need Better Therapies
Rheumatologists have few options to manage AS symptoms and disease progression, says Dr. Haroon. First-line therapy is an NSAID to control inflammation and pain, followed by TNF inhibitors if a patient does not respond.9
“For [AS] treatment, we have been extrapolating drugs used in [rheumatoid arthritis (RA)]. NSAIDs help only a small proportion of patients with AS. Disease-modifying antirheumatic drugs [that are] helpful in RA have no efficacy in axial disease,” he says. “TNF inhibitors and IL-17 inhibitors control disease symptoms in only 50–60% of patients. There are no good prognostic algorithms for predicting treatment response in AS.”
MIF could be a promising target for the development of a new, more effective therapy for these patients and a way to better identify patients at risk for rapid disease progression, he says.
“MIF is the first innate immune cytokine … shown to drive both disease processes directly,” Dr. Haroon says. “MIF appears to be upstream of both TNF and Th17 cytokines. MIF may not only be a good target for treatment, it may also be a good biomarker to identify AS patients who have a particularly aggressive disease course. These patients could be selected for close follow-up and aggressive treatment, and enrolled in targeted therapeutic trials.”
Susan Bernstein is a freelance journalist based in Atlanta.
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