Cryoneurolysis Shows Promise in Treating Knee Arthritis

Norra MacReady

March 31, 2017

A little-known treatment shows promise in decreasing pain and disability associated with mild to moderate knee osteoarthritis (OA) for up to 5 months, the authors of a new randomized controlled trial report.

In an intention-to-treat analysis, cryoneurolysis at the infrapatellar branch of the saphenous nerve was associated with a significant decrease in pain compared with patients undergoing a sham procedure, Richard Radnovich, DO, and colleagues write in an article published online March 21 in Osteoarthritis and Cartilage.

These findings compare favorably to the effects of other treatments for knee OA, including nonsteroidal anti-inflammatory drugs, opioids, and viscosupplementation, they add. Cryoneurolysis might be a good choice, "particularly as part of a changing healthcare landscape that seeks to identify effective and safe non-pharmacological options to treat chronic pain."

Cryoneurolysis consists of freezing and essentially destroying the peripheral nerve axon, thereby "allowing for complete regeneration and functional recovery of the nerve," the authors explain. "The nerve axon is able to regenerate along the previously established path to eventually reinnervate the sensory receptor."

In this study, the investigators used the iovera° device (Myoscience, Inc), which consists of a handpiece equipped with a nitrous oxide cartridge and three closely spaced 27-gauge closed-end needle tips. The nitrous oxide flows from the cartridge to the needle tips, creating a "highly localized cold zone."

Myoscience, Inc, which makes the device, funded the study. "There are other cryo devices; the size and ease of use of this device are attributes that make it different," Dr Radnovich, of the Injury Care Medical Center, Boise, Idaho, told Medscape Medical News.

However, he added, "the device is not yet widely available, and...very few physicians have access to, or even know about, this treatment."

Multicenter Trial

Dr Radnovich and colleagues enrolled 180 patients in the double-blind, sham controlled trial, conducted at 17 sites around the United States between April 2013 and June 2016. Patients ranged in age from 33 to 75 years, met the American College of Rheumatology clinical and radiographic criteria for knee OA, and were ambulatory without assistive devices. Exclusion criteria included gross knee deformity and body mass index of 35 kg/m2 or more.

The primary endpoint was change in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score from baseline to day 30 after the procedure. WOMAC is a 24-item disease-specific instrument that assesses pain, stiffness, and function, with higher scores indicating worse outcomes.

The researchers randomly assigned participants 2:1 to either cryoneurolysis or sham treatment. Before the procedure, cutaneous and subcutaneous lidocaine was administered to all patients to maintain blinding. Each patient then underwent either cryoneurolysis or sham treatment with an instrument designed to look and sound identical to the active iovera° device.

The two patient groups did not differ significantly with respect to personal or demographic characteristics, or on baseline scores of pain, stiffness, or functional limitations.

During the follow-up period, the patients could not use any adjunctive treatment, other than acetaminophen tablets provided, and were monitored by the investigators. They were instructed to stop taking acetaminophen and any other pain medication for knee OA before each follow-up visit.

The analysis included 121 patients who underwent active cryoneurolysis and 59 who underwent the sham treatment. The mean treatment duration was 23 minutes.

At day 30, patients in the active treatment group showed a least squares (LS) mean change in the WOMAC pain score of −16.65 points compared with an LS mean of −9.54 among the sham group (LS mean difference, −7.12; 95% confidence interval [CI], −11.01 to −3.22; P = .0004).

The differences remained statistically significant at the 60- and 90-day follow-up visits, but were no longer significant by 120 days.

Similar patterns were seen in the total WOMAC and the physical function scores. On the WOMAC stiffness score, the LS mean difference at 30 days was −2.32 (95% CI, −3.97 to −0.68; P = .0060), −1.64 (95% CI, −3.36 to 0.08; P = .0615) at 60 days, and −1.83 (95% CI, −3.50 to −0.15; P = .0325) at 90 days. It was no longer statistically significant at 120 days.

In a secondary analysis, patients in the active treatment group who continued to experience benefits at day 120 "maintained statistically significant improved WOMAC pain subscale scores at Day 150, compared to the sham treatment group," the authors write.

On the visual analog pain score, the LS mean difference between the treatment and sham groups was −12.25 (95% CI, −21.16 to −3.35; P = .0073) at 30 days. There were no significant differences between the groups at days 60, 90, or 120.

The adverse effects most commonly reported by both groups were usually mild and included bruising, local pain, numbness, and swelling, Dr Radnovich said. "The potential for adverse events or side effects of this treatment appear to be the same or less than other available treatments for pain associated with knee OA."

He added, "Most patients were satisfied with treatment results."

Independent Experts Weigh In

"This was a very carefully performed study, and I have no critique of the methodology or selection criteria," Roy Altman, MD, told Medscape Medical News.

However, Dr Altman, professor of medicine, rheumatology, and immunology at the University of California, Los Angeles, School of Medicine, questioned the use of a one-way analysis of variance design, saying that such a formula allowed the investigators to show when patients got better, but not worse. "I didn't see the justification for that, and of course it gives them a clear-cut statistical advantage."

Nevertheless, he said, "it was clear that at least by the first follow-up examination at 30 days, the results were significantly better compared with the control group." In particular, the 12-point difference seen in visual analog pain scores at 30 days "is a difficult achievement in an osteoarthritis study."

For patients seeking rapid pain relief, "this may be one alternative, once more research has been completed," Lynn Millar, PT, PhD, told Medscape Medical News. But "my concern as a therapist is this is simply blocking the sensation of pain, which will eventually return as the nerve regenerates, and anytime sensation is diminished, there is a possibility of decreased muscular control."

"Exercise and or weight loss have also been shown to reduce pain, and improve function," said Dr Millar, chair of the Department of Physical Therapy, Winston-Salem State University, North Carolina. Neither she nor Dr Altman were involved in the cryoneurolysis study.

Dr Altman and Dr Millar also emphasized caution when interpreting these findings because of the significant placebo effect associated with osteoarthritis therapies. "In studies of topical or intra-articular treatments, the placebo effect can be as high as 60% or 70%, so to show a separation from control is really hard," Dr Altman told Medscape Medical News.

Still, he concluded, "I would be willing to learn more about this. If we can find anything that works, I'm willing to try it."

Funding for this study was provided by Myoscience, Inc, which makes the iovera° device. Dr Radnovich and one other study author are paid consultants to and/or speakers for and stockholders in Myoscience. A third author is a paid consultant to and has received royalties from, Arthrex. The remaining authors, Dr Altman, and Dr Millar have disclosed no relevant financial relationships.

Osteoarthritis Cartilage. Published online March 21, 2017. Abstract

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