Shimizu and colleagues in 2003 found a high prevalence of obstructive sleep apnea among patients with RA and that treatment with continuous positive airway pressure resulted in reduced RA activity.7 Pilot research presented at the 2014 ACR/ARHP Annual Meeting by Stavrakis and colleagues suggested that HRV measure could provide a sensitive inflammatory biomarker in systemic lupus erythematosus (SLE).8 Several conditions, such as sleep apnea and restless legs syndrome, are linked with a decreased parasympathetic tone that can be assessed by HRV.
Dr. Holman has established a research and diagnostics company, Inmedix LLC, that is exploring the efficacy of measuring HRV with the proprietary Omegawave device to help predict patient outcomes to anti-TNF therapy. The company is working to obtain FDA 510(k) clearance on the core technology platform, called ANS Neuroscan, and plans to conduct multicenter clinical trials. Eventually, the company hopes to gain FDA premarket approval (PMA) for the ANS Neuroscan as a patient management tool for RA treatment and, later, for SLE and multiple sclerosis.
Robert Ettlinger, MD, retired after 35 years as a rheumatologist in Tacoma, Wash., and who now serves on the Inmedix scientific advisory board, says the field of rheumatology continues to search for a reliable marker that could help identify which patients are likely to respond to certain therapies. “When treatment with regular DMARDs [disease-modifying antirheumatic drugs] and three different classes of biologics has failed and patients still have active disease, and you can’t get them down from 15 mg of prednisone, then you start thinking that ‘this chemistry set I am using in this patient is not working.’”
“Dr. Holman feels that if we know from the outset who the nonresponders are going to be, with a very high predictive value [by assessing parasympathetic tone via HRV], then maybe we wouldn’t keep knocking our head against the wall trying all these different therapies,” Dr. Ettlinger says. “We could cut to the chase with the first therapy adjunctively that could be expected to enhance this cholinergic antiinflammatory reflex, whether it be chemical or mechanical.”
Rheumatologist Lee S. Simon, MD, a former division director of the FDA’s Analgesic, Anti-inflammatory and Ophthalmologic Drug Products and now a principal at SDG LLC, FDA regulatory and clinical development consultants, says that some additional research with larger groups of patients will be needed before Inmedix can gain PMA for use of the HRV device for this indication. If future large clinical trials prove its effectiveness in predicting responsiveness to therapy, “that could be very helpful,” he says.
