Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To identify a treatment-responsive population for botulinum toxin type A (BoNTA) and to evaluate the safety and efficacy of 3 different doses of BoNTA as prophylactic treatment of chronic daily headache (CDH).


METHODS
A randomized, double-blind, placebo-controlled study of BoNTA in patients with CDH was conducted from July 6, 2001, through November 7, 2003, at 28 North American study centers. Eligible patients were injected with BoNTA at 225 U, 150 U, 75 U, or placebo and returned for additional masked treatments at day 90 and day 180. Patients were assessed every 30 days for 9 months. The primary efficacy end point was the mean change from baseline in the frequency of headache-free days at day 180 for the placebo nonresponder group.


RESULTS
For this study, 702 patients were enrolled and randomized. The primary efficacy end point was not met. Mean improvements from baseline at day 180 of 6.0, 7.9, 7.9, and 8.0 headache-free days per month were observed in the placebo nonresponder group treated with BoNTA at 225 U, 150 U, 75 U, or placebo, respectively (P=.44). An a priori-defined analysis of headache frequency revealed that BoNTA at 225 U or 150 U had significantly greater least squares mean changes from baseline than placebo at day 240 (-8.4, -8.6, and -6.4, respectively; P=.03 analysis of covariance). Only 27 of 702 patients (3.8%) withdrew from the study because of adverse events, which generally were transient and mild to moderate.


CONCLUSIONS
Although the primary efficacy end point was not met, all groups responded to treatment. The 225 U and 150 U groups experienced a greater decrease in headache frequency than the placebo group at day 240. The placebo response was higher than expected. BoNTA was safe and well tolerated. Further study of BoNTA prophylactic treatment of CDH appears warranted.
Silberstein
Stephen D
SD
Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Stephen.Silberstein@jefferson.edu
Stark
Stuart R
SR
Lucas
Sylvia M
SM
Christie
Suzanne N
SN
Degryse
Ronald E
RE
Turkel
Catherine C
CC
D000293:Adolescent; D000328:Adult; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D020773:Headache Disorders / Q000517:prevention & control*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A