How safe and effective is TGF-beta for treatment of keloids and hypertrophic scars?

Updated: May 29, 2020
  • Author: Brian Berman, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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A new antifibrotic product, avotermin (Juvista, Renovo; Manchester, United Kingdom) has been extensively studied. Avotermin is derived from human recombinant TGF-beta3. This product has shown promise in a phase I trial and 2 phase II trials completed in the United Kingdom. In these studies, wounds treated with avotermin showed a statistically significant improvement in scar appearance, with a response rate of greater than 70%. After analyzing safety data on more than 1500 human subjects, avotermin does not seem to have safety or tolerability issues for use in the prevention or reduction of scarring.

In a randomized, double-blind, placebo-controlled, within-patient, phase II trial to investigate the safety and efficacy of 200 ng per 100 μL per linear cm of wound margin of avotermin when administered twice following scar revision surgery, the overall analysis showed that the primary endpoint (ie, photographic evaluation by a lay panel over a period from week 6 to month 7 postsurgery using a visual analogue scale) was met (P = .038). Investigator assessment at 7 months postsurgery using a visual analogue scale also obtained statistical significance (P = .036). Approximately 75% of the 7-month scars assessed from avotermin-treated wounds were considered to have a structure more like normal skin compared with the placebo in the histopathological analysis. [64]

Bush et al evaluated 71 subjects (aged 18-45 y) who received avotermin at 50 or 200 ng/100 μL/linear centimeter of wound margin. Incisional wounds on the inner aspect of each upper arm were randomized to receive the following: no injection (standard wound care only), 1 intradermal injection of avotermin or placebo (immediately before surgery), or 2 injections of avotermin or placebo (immediately before surgery and 24 h later). Avotermin at 200 ng/100 μL/linear centimeter, administered once or twice, achieved significant improvements in scar appearance compared with controls (P< .02 for all comparisons). The 50-ng dose, administered twice, achieved significant improvements in scar appearance versus placebo (P = .043). Treatment was well tolerated. [65]

A double-blind, randomized study (ie, RN1001-0042) evaluated the efficacy and safety of 4 doses of avotermin given once. A total of 156 patients undergoing bilateral surgery to remove varicose leg veins by saphenofemoral ligation and long saphenous vein stripping were studied. Four different doses of avotermin were administered (5, 50, 200 or 500 ng per 100 µL, at 100 µL per linear cm of wound margin). The primary efficacy variable was lay panel Total Scar Score (ToScar) assessed between 6 weeks and 7 months. Avotermin 500 ng significantly improved groin scar appearance compared with placebo (mean lay panel ToScar difference 16·49 mm; P = .036). Avotermin 500 ng per 100 µL per linear cm of wound margin given once is well tolerated and significantly improves scar appearance. [65, 66, 67, 68, 69]

TGF therapy is currently being studied in ongoing clinical trials for use as an adjuvant treatment following excision of earlobe keloids. [70, 71, 72]

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