Approaches to Treatment with Botulinum Toxin Type B

The approach to treatment with botulinum toxin type B involves...

• Establishment of treatment goals
• Determination of appropriate dosing
• Appropriate muscle selection for injection sites. (There are 52 muscles involved in cervical function, such as controlling the rotation, extension, and tilting of the head.)
• Appropriate selection of muscles based on patient's pain and the location of the painful area(s)
• Further consideration of dose and concentration for each muscle
• Possible administration into multiple sites within each affected muscle
• Follow-up with the physician regarding benefits or adverse effects

MYOBLOC is injected directly into the dystonic muscle. The injected solution weakens the muscle by "chemically disconnecting" the muscle from its nerve supply and the chemical messages that it sends to the muscle.

The efficacy of MYOBLOC™ in the treatment of cervical dystonia has been demonstrated in three pivotal double-blind trials. Lew et al. enrolled 122 patients with idiopathic cervical dystonia (CD) in a single-treatment, double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B. Both botulinum toxin type A-responsive and resistant patients were enrolled. Patients received intramuscular injections of 2,500 U, 5,000 U, or 10,000 U of botulinum toxin type B or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), with measurement of total score at four weeks following drug administration. TWSTRS is a validated rating scale for determining the efficacy of botulinum toxin treatment. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, as well as Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events.

Improvement significantly greater than placebo was reported in all active treatment arms, with magnitude of improvement increasing with escalating doses. The best response was seen in patients receiving 10,000 Units. These patients experienced a five-fold greater improvement than placebo-treated patients (p<0.0005). Dry mouth (27%) and dysphagia (33%) were the most common adverse events seen in patients at the highest dose, versus 0% dry mouth and 3% dysphagia in the placebo group. Injection-site pain occurred in 17% of toxin-treated patients versus 10% of placebo-treated patients. The authors concluded that, at the doses tested, botulinum toxin type B is safe, well tolerated, and efficacious in the treatment of cervical dystonia.

Brin et al. enrolled 77 botulinum toxin type-A resistant CD patients into a 16-week, single-treatment, double-blind, placebo-controlled trial of botulinum toxin type B After resistance to therapy was confirmed with the frontalis-type A test, patients received either placebo or 10,000 U of the type B toxin, which was administered in two to four muscles. TWSTRS-Total score was the primary efficacy measurement. Patients were assessed at baseline and at weeks 2, 4, 8, 12, and 16. Additional assessment measures included the Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment, and adverse events.

Improvements in severity, disability, and pain were documented in the botulinum toxin type B-treated group. TWSTRS-Total scores were improved in this group at 4 weeks (p = 0.0001), 8 weeks (p = 0.0002), and 12 weeks (p = 0.0129). All three visual analog scales demonstrated improvements at 4 weeks (p < 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were reported more commonly in the botulinum toxin type B group. The authors concluded that botulinum toxin type B is safe and efficacious for the management of patients with type A-resistant cervical dystonia, with an estimated duration of treatment effect of 12 to 16 weeks.

Brashear et al. enrolled 109 botulinum toxin type A-responsive patients with CD in a 16-week, randomized, multi-center, single treatment, double-blind, placebo-controlled trial of botulinum toxin type B. Placebo, 5,000 U, or 10,000 U of botulinum toxin type B toxin was administered to two to four muscles. TWSTRS-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded at baseline and at weeks 2, 4, 8, 12, and 16.

The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary comparison (10,000 U versus placebo), highly significant differences were noted for the TWSTRS-Total at baseline to week 4 (p = 0.0004) and for supportive secondary Patient Global Assessment at baseline to week 4 (p = 0.0001). Improvement in pain, disability, and severity of CD occurred for patients who were treated with botulinum toxin type B when compared with placebo-treated patients. Overall, improvements associated with botulinum toxin type B treatment were greatest for patients who received the 10,000 U dose. The duration of treatment effect was 12 to 16 weeks for both doses of toxin. The authors concluded that botulinum toxin type B is safe and efficacious at 5,000 U and 10,000 U for the management of patients with type A-responsive cervical dystonia.

	Dosing of Botulinum Toxin Type B