Researchers investigate steroid alternatives for managing keloids

Miami - Treating keloids can be challenging because there is a high rate of recurrence of them, but promising therapies lie on the horizon, such as transforming growth factor-beta 3.

A compound known as avotermin (TGF-beta 3, Juvista, Renovo), a recombinant, active, transforming human growth factor beta 3, has been tested to accelerate the improvement in scarring, according to Heather Woolery-Lloyd, M.D., dermatologist and director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, Miami.

"It will be interesting to see if it (TGF-beta 3) will have an effect in terms of scar revision, because then we will find out how well it works in patients that have a predisposition to hypertrophic scars," Dr. Woolery-Lloyd says.

Avotermin has been explored in phase 2, double-blind, placebo-controlled, randomized trials. It has demonstrated in trials that intradermal injection given at or immediately subsequent to surgery was safe and resulted in an improvement in scar appearance that was statistically significant. At present, a phase 3 efficacy trial in scar revision is under way.

Steroid treatment
Intralesional steroids represent the mainstay of treatment for keloids that appear on the body, and a series of treatments need to be administered to treat the keloids. The concentrations typically range from 10 mg to 40 mg per cc. There are unwanted side effects that can occur with the injection of intralesional steroids, such as hypopigmentation and thinning of the skin, Dr. Woolery-Lloyd says.

"You can get atrophy of the skin," she says.

Cryotherapy, another treatment for keloids, can also produce pigmentary changes.

Because there are some undesired side effects with current therapies, investigations of novel approaches to manage keloids are ongoing.

Keloid location matters
Another therapy that is regarded as innovative to treat keloids is imiquimod (Aldara, Graceway), Dr. Woolery-Lloyd says. One study published in 2005 found that the use of imiquimod 5 percent cream was an effective adjuvant to prevent the recurrence of keloids on the earlobes after they had been surgically removed. After 24 weeks, there was no recurrence detected. Half of the patients, however, developed pigmentary alteration.

According to Dr. Woolery-Lloyd, earlobe keloids have lower recurrence rates than other parts of the body, so it would be useful to also examine efficacy in truncal keloids.

"The location of the body makes a difference in terms of how likely (the keloids) recur," she says. "They are least likely to recur on the ear. The fact that imiquimod did well on the ears is helpful, but treating keloids at other locations, such as the chest or back, is a real challenge. If the keloids appear on the body, for instance on the trunk, the recurrence rate, regardless of treatment, is much higher."

Botulinum toxin type A is indicated for the treatment of axillary hyperhidrosis and is used off-label to treat other conditions. Botox (onabotulinumtoxinA, Allergan) immobilizes local muscles, which may decrease skin tension and reduce inflammation. In one study of 19 patients with hypertrophic scars, Botox was administered as an intralesional injection at one-month intervals for three months. Investigators found the erythema score, itching sensation and pliability after injection of Botox were all lower than before injection in a statistically significant fashion.

"Botox is used in everyday practice, but it's not something people think about for keloids," Dr. Woolery-Lloyd says.

While it may hold up as an effective treatment option for hypertrophic scars, there is a financial cost associated with Botox, which may not make it an appealing management choice for some patients, she says.

Interleukin-10 studies
Interleukin-10 (IL-10) has been regarded as a cytokine that suppresses the inflammatory response. In animal studies, wound sites were injected with IL-10 prior to wounding. At three days post-wounding, the release of inflammatory mediators had fallen, there was no collagen deposition, and there was restoration of the normal dermal architecture when compared to wounds injected with vehicle. Phase 2 trials are being conducted to determine which of eight intraepidermal doses are best-tolerated and most efficacious in reducing scars. "

In animal models, wounds were found to do better with IL-10 treatment than with placebo alone," Dr. Woolery-Lloyd says.

Other therapies that have been cited in the literature as being used to treat keloids include calcineurin inhibitors, retinoids and antihistamines, but there are no significant clinical data to support advancing exploration with these therapies at this time.

Disclosures: Dr. Woolery-Lloyd is an investigator for Organogenesis.