To examine the efficacy and safety of and satisfaction with botulinum toxin type A (BoNTA; BOTOX: Allergan, Inc., Irvine, CA) for prophylactic treatment of migraine headache in patients previously failing prophylaxis because of issues pertaining to compliance. Background.- Numerous factors (eg, adverse effects, tolerability, cost, frequency of dosage, hesitancy to take daily medication, failure to complete treatment) negatively influence compliance with the preventive pharmacology for migraine prophylaxis. BoNTA may offer benefit in improving compliance because of its long duration of action, injectable route of administration, and its tolerability (adverse event [AE]) profile.
This was a randomized, double-blind, single-center, placebo-controlled study (months 1 to 3) of BoNTA with a cross-over to open-label BoNTA treatment (months 4 to 6). Criteria for enrollment included patients with disabling headache (International Headache Society, International Classification of Headache Disorders [ICHD-I] diagnosis 1.1, 1.2, 1.7, or 2.2, and Headache Impact Test [HIT]-6 scores >/=56) previously failing prophylaxis because of compliance, tolerability, or adherence issues. After baseline evaluation, subjects were randomized 2 : 1 to a single set of BoNTA (139 units [U] total; 17 sites/6 muscle groups) or placebo injections. After month 3, only placebo-treated subjects were eligible to receive BoNTA in the open-label continuation study. Treatment outcomes were evaluated by headache episodes and days and maximum headache severity. Headache impact was assessed by the HIT-6, Migraine Disability Assessment (MIDAS) score, and Quality of Life (QoL) questionnaires. Treatment satisfaction was assessed with the Migraine Impact Questionnaire (MIQ), which included MIDAS and QoL.
Of the 73 subjects screened, 61 (40 BoNTA; 21 placebo) with migraine headache diagnosis 1.1 and 1.2 who met all study criteria were enrolled in the 3-month, blinded study, with 54 completing the study; 19 of 21 placebo-treated subjects participated in the open-label period (months 4 to 6), with 18 completing the study. Between-group comparisons, demonstrated through analysis of the subjects' headache diaries, did not reach statistical significance at months 1 to 3 for the number of headache episodes or days (primary endpoint). At month 2, a decrease from baseline in the number of headache episodes (-0.99 +/- 2.38; P = .0147 vs 0.42 +/- 3.23; P = not significant [NS]) and headache days (-1.52 +/- 3.84; P = .0194 vs 0.23 +/- 4.67; P = NS) was noted in the BoNTA-treated subjects but not in the placebo-treated subjects, respectively. During the open-label study, BoNTA-treated subjects had a decrease in the number of headache episodes at months 5 and 6 (-1.58 +/- 2.88 and -1.58 +/- 2.85, respectively; P < .05 vs baseline for both) and headache days at months 5 and 6 (-2.84 +/- 4.47 and -2.73 +/- 4.86, respectively; P < .05 vs baseline for both). BoNTA did not affect maximum headache severity compared with baseline or placebo during the first 3 months of the study. A decrease in HIT-6 scores was significantly greater for BoNTA-treated subjects than for placebo-treated subjects at month 3 (-7.77 vs -3.58, P = .0466). Within-group decreases in HIT-6 scores were significant in BoNTA-treated subjects during each month of the blinded trial (-5.10 +/- 8.85, -6.63 +/- 7.49, -7.77 +/- 8.78 for months 1 to 3, respectively; P < .0001 for all vs baseline) and throughout the open-label portion of the study (-7.89 +/- 6.48, -10.39 +/- 10.81, -9.00 +/- 11.12 for months 4 to 6, respectively; P < .01 for all vs baseline). The within-group decrease in placebo-treated subjects was significant at months 1 and 3 (-3.35 +/- 6.07 and -3.58 +/- 5.40, respectively; P < .05 for both). At 3 months, BoNTA was significantly better than placebo (P = .001) in the reduction of MIDAS total score. The change from baseline in the MIDAS total scores was significant in BoNTA-treated subjects (-21.62 +/- 38.70; P < .0001) but not in placebo recipients (4.76 +/- 18.85; P = NS). BoNTA-treated subjects showed improvement in 11 of 13 and 7 of 13 assessments of treatment satisfaction in MIQ at months 3 and 6, respectively, while the placebo group showed no improvement at any measured time interval in the study. At month 3 (blinded period), there were no treatment-related AEs reported in both groups. However, there were 18 possible/probable occurrences of treatment-related AEs in the BoNTA group. At month 6 (open-label period), 4 treatment-related AEs were reported, along with 2 possible occurrences. The majority of treatment-related AEs were transient and mild to moderate in severity, with no subjects discontinuing the study because of AEs.
BoNTA-treated subjects showed improvements from baseline in measures of headache frequency, and improvements from baseline and in comparison with placebo treatment in headache impact and treatment satisfaction at multiple time points in this study. However, BoNTA-treated subjects did not differ from placebo-treated subjects in measures of headache frequency and severity. BoNTA may be a useful treatment option for headache patients demonstrating poor compliance, adherence, or AE profile with oral prophylactic regimens.