Medscape Conference Coverage, based on selected sessions at the:
American Association of Pain Management (AAPM) 20th Annual Clinical Meeting
This coverage is not sanctioned by, nor a part of, the American Association of Pain Management.
From Medscape Medical News
High-Dose Capsaicin Patch Provides Durable Postherpetic Neuralgia Pain Relief
Nancy A. Melville
Authors and Disclosures
October 15, 2009 (Phoenix, Arizona) A high-concentration capsaicin patch that is applied to the skin for just an hour can provide up to 3 months of pain relief for patients with postherpetic neuralgia, according to several studies presented here at the American Association of Pain Management (AAPM) 20th annual clinical meeting.
Capsaicin, the compound known for making peppers such as jalapeos hot, is commonly sold in low concentrations in creams for arthritis and other painful conditions, but the patch, called NGX-4010 and commercially marketed as Qutenza (NeurogesX, Inc.), contains 8% capsaicin, a much higher concentration than is found in over-the-counter products, Misha-Miraslav Backonja, MD, a coauthor of the studies and a professor in the Department of Neurology at the University of Wisconsin in Madison, told meeting attendees.
"There are other preparations that contain capsaicin, including gels and creams, but this is a single application [of a concentration] that is 80 times [higher] than the highest concentration in the gels or creams," he said. "The product is really different from anything else in pain medicine."
In the phase 3 studies reported at the AAPM meeting, researchers looked at the safety and efficacy of the patch. The product is already available in Europe
The first study was designed to evaluate the patch's effect on neurosensory function in patients with postherpetic neuralgia. Researchers analyzed data from 4 double-blind 12-week controlled studies that consisted of 738 patients treated with NGX-4010 (8% capsaicin w/w) and 531 control patients treated with a low-concentration capsaicin patch (0.04% capsaicin w/w).
The study also looked at data from 2 open-label repeat-treatment studies in which patients could receive up to 4 treatments over a 1-year period.
The results showed that most NGX-4010 and control patients experienced no change in light brush, pin-prick, vibration, or warmth sensations from baseline to week 12. Among those that did experience changes, the NGX-4010 patients showed improvement in light brush (21.3% vs 14.5%), vibration (24.1% vs 16.4%), pinprick (23.1% vs 20.0%), and warmth (19.6% vs 17.6%) sensations.
"There was no evidence of a problem when the product was developed, but the expected pharmacological effect was that it could lead to loss of small neurosensory fibers in the top layers of the skin," Dr. Backonja said.
"So the concern was that if something such as capsaicin in high concentrations could cause loss of nerve fibers, you might end up with loss of function, but that wasn't the case. We found that, not only was there not a loss of function, there was in fact improved function in a subset of patients. That will be something important to submit for further study."
A second study, evaluating the safety and efficacy of the patch, included data from 4 double-blind, controlled postherpetic neuralgia studies with 597 patients receiving a single NGX-4010 treatment and 530 control patients receiving the lower-dose (0.04% w/w) patches.
Over the course of the 12-week studies, the patients recorded daily ratings of pain in the previous 24 hours on an 11-point pain rating scale. The mean percentage change in the pain score was significantly greater for patients receiving the NGX-4010 patch than for those receiving the control patch during weeks 2 to 8 (31.2% vs 22.3%; P < .0001) and during weeks 2 to 12 (31.3% vs 22.6%; P < .0001).
On the secondary end point the proportion of patients with a reduction in mean Numeric Pain Rating Scale (NPRS) score that was equal to or greater than 30% the researchers found that during weeks 2 to 8, 43.6% of patients receiving the NGX-4010 patch had a significant (>30%) reduction in NPRS score, compared with 33.6% those receiving the control patch (P = .0004). From weeks 2 to 12, 44.9% of the NGX-4010 group had a significant change in NPRS score, compared with 35.3% of the control group (P = .0006).
On the Patient Global Impression of Change, results showed that those in the NGX-4010 group consistently reported being "very much" or "much" improved throughout the study, compared with the control group. At week 8, 37.3% of the NGX-4010 group and 24.8% of the control group reported they were "much" or "very much" improved. At week 12, 36.5% and 23.7% of the high-dose and control groups, respectively, reported being "much" or "very much" improved (P < .0001 for both).
The most common adverse events in the NGX-4010 group were pain around the site of the patch, with 42% reporting application site pain, compared with 19% in the control group. However, all patients were able to tolerate the treatment, Dr. Backonja said.
"I actually thought patients would not be able to tolerate the pain at the higher dose, but most patients reported pain of just about 6 or 7 on a 1- to 10-[point] scale and they were able to tolerate it."
Topical lidocaine gel is applied for an hour before the patch is applied, and ice can be used to further reduce pain from the application, which eases after about 1 to 2 days, Dr. Backonja added.
Capsaicin's mechanism of action in providing pain relief involves the activation of TRPV1 receptors on nociceptive sensory nerve fibers, resulting in a depolarization and action potential initiation. Prolonged exposure to capsaicin causes TRPV1-containing sensory axons to lose end branches and terminals, resulting in a reduction of pain transmission, according to the researchers.
The patch could play an important role in the treatment of postherpetic neuralgia, either on its own or in combination with other therapies, he said.
"This is a product that is different from anything else in pain medicine in the sense that it's a patch that's applied 1 time only and leads to prolonged pain relief," he said. "It lends itself either as a first-line treatment for localized peripheral neuropathic pain or in combination with other therapies because, being topical therapy, it requires just 1 application; after it reduces pain, the added other medicines could be used at lower doses."
The idea of capsaicin as a treatment for postherpetic neuralgia has been around for several decades; however, early experimentations were considered just too painful, said R. Norman Harden, MD, director of the Center for Pain Studies at the Rehabilitation Institute of Chicago in Illinois, who experienced the treatment first-hand.
"I found myself being 'volunteered' for one of the early capsaicin injections at the [National Institutes of Health], and I can tell you it was incredibly, intensely painful. But of course they didn't offer me any lidocaine at the time. You'd really have to have lidocaine to make it bearable."
"The concept is that capsaicin kind of sucks substance P, related to the transmission of pain information, out of the nerve endings, which makes them all fire to the point of exceeding their metabolic capability, and then they simply shut down and can't produce substance P any more," he explained.
The idea of a therapy such as the NGX-4010 patch being capable of muting pain for postherpetic neuralgia patients for 3 months would be highly welcome because of the current lack of any consistently reliable treatment, Dr. Harden added.
"Postherpetic neuralgia is one of those unmet needs in pain management," he emphasized. "With anything that's currently on the market, only about a third of people are going to get a profound relief from their pain. So this is quite encouraging."
The study received funding from NeurogesX, Inc. Dr. Backonja disclosed that he has been an investigator for NeurogesX, Inc. Dr. Harden disclosed that he has received research support from GlaxoSmithKline.
American Association of Pain Management (AAPM) 20th annual clinical meeting: Abstracts 53 and 54. Presented October 9, 2009.