|
AVOTERMIN - Un
farmaco progettato per ridurre le cicatrici
Mirella Milioto - 23/04/2009
Prophylactic administration of avotermin for improvement of skin scarring: three
double-blind, placebo-controlled, phase I/II studies
Prof Mark WJ Ferguson DMedSci a b , Jonathan Duncan MD b c, Jeremy Bond MB b d,
James Bush MB b, Piyush Durani MD b c, Karen So MB b, Lisa Taylor MB b d,
Jonquille Chantrey MB b c, Tracey Mason PhD b, Gaynor James MSc b, Hugh Laverty
PhD b, Nick L Occleston PhD b, Abdul Sattar PhD b, Anna Ludlow PhD b, Sharon O'Kane
PhD b
The Lancet, volume
373, issue 9671, pages 1264-1274, 11 April 2009
Summary: Research into mechanisms of skin scarring identified transforming
growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar
improvement with avotermin (recombinant, active, human TGFβ3).
Methods
In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations
ranging from 0·25 to 500 ng/100 μL per linear cm wound margin) was administered
to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h
later, in healthy men and women. Treatments (avotermin and placebo or standard
wound care) were randomly allocated to wound sites by a computer generated
randomisation scheme, and within-participant controls compared avotermin versus
placebo or standard wound care alone. Primary endpoints were visual assessment
of scar formation at 6 months and 12 months after wounding in two studies, and
from week 6 to month 7 after wounding in the third. Investigators, participants,
and scar assessors were blinded to treatment. Efficacy analyses were intention
to treat. These studies are registered with ClinicalTrials.gov, numbers
NCT00847925, NCT00847795, and NCT00629811.
Results
In two studies, avotermin 50 ng/100 μL per linear cm significantly improved
median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14;
p=0·001) at month 6 and 8 mm (−29 to 18; p=0·0230) at month 12. In the third,
avotermin significantly improved total scar scores at all concentrations versus
placebo (mean improvement: from 14·84 mm [95 % CI 5·5—24·2] at 5 ng/100 μL per
linear cm to 64·25 mm [49·4—79·1] at 500 ng/100 μL per linear cm). Nine [60%]
scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less
abnormal orientation of collagen fibres in the reticular dermis versus five
[33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL
per linear cm improved VAS score by 16·12 mm (95% CI 10·61—21·63). Adverse
events at wound sites were similar for avotermin and controls. Erythema and
oedema were more frequent with avotermin than with placebo, but were transient
and deemed to be consistent with normal wound healing.
Interpretation:
Avotermin has potential to provide an accelerated and permanent improvement in
scarring.
|
