Headache medicine specialists have used onabotulinumtoxinA off label as an efficacious treatment for headache prophylaxis for a number of years.

The pooled results from the double-blind, randomized, placebo-controlled, Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) 1 and 2 trials (Headache 2010;50:921-36) demonstrated that onabotulinumtoxinA (Botox) is an effective prophylactic treatment for chronic migraine (CM). On Oct. 15, 2010, the Food and Drug Administration (FDA) approved Botox “to prevent headaches in adult patients with chronic migraine.” Botox is the first and only FDA-approved medication for the treatment of this group of chronic headache patients.

Dr. Stuart B. Black
The PREEMPT studies also defined the appropriate patient selection, injection sites, dosages, and technique. Specific fixed sites for the pericranial injections were established as an effective injection paradigm, but as the treatment approach evolved, other sites corresponding to the location of pain and tenderness in individual patients were added. Therefore, a combination of a fixed-site, fixed-dose and follow-the-pain injection protocol was found to provide the optimal benefit.

The doses range from 155 U to 195 U administered IM across seven head and neck muscles every 12 weeks for up to five treatment cycles. This was also an important contribution of the PREEMPT study because prior preliminary reports evaluating Botox not only included a range of primary headache disorders but also employed different medication doses and injection sites.

As additional data are mined from the PREEMPT trials, it is important to recognize that Botox is still only part of a comprehensive management program that is required in the holistic care of most patients with CM. For this reason, many of the leaders in headache medicine emphasize that this treatment for CM should be utilized only by those specialists who have experience in the comprehensive management of this type of patient population.

There remain barriers in the accessibility of Botox for many patients. The literature estimates the cost of Botox therapy at about $1,300-$1,500 per treatment session. Even though one can justify that expense by a significant reduction in direct and indirect medical costs related to CM, many insurance carriers still make it difficult to obtain preapproval for treatment.

For physicians in private practice, authorization usually requires an experienced staff member who can dedicate the necessary time to obtain precertification. This process may include a letter of medical necessity in addition to the procedure code, diagnosis code, and medications previously prescribed. The submitted medical record also must document the diagnosis of CM according to the International Classification of Headache Disorders, second edition. Specifically, patients with CM must experience 15 or more headache days per month for at least 3 months, with at least 8 days in which headaches were classified as migraine without aura or headaches that respond to migraine-specific medications.

Although evidence-based medicine can justify the use of Botox as a second-line therapy if a medication such as topiramate fails, many insurance precertification requirements include only “adults who have tried and failed trials of at least 3 classes of migraine headache prophylaxis medications of at least 2 months (60 days) duration for each medication.” These criteria are mandated, even though none of the other listed medications are proven effective against CM and none are FDA approved for the indication.

There are also situations in which medical facilities may charge much more than $1,500 per treatment, which could leave a less informed patient with a significant out-of-pocket expense. Some insurance companies require use of their pharmacy to supply the Botox, which can result in administrative difficulties in the coordination of care.

The PREEMPT studies document that Botox is a major step forward in the treatment of CM. The potential economic issues related to accessibility of treatment are greatly overshadowed by the high quality of research done by the lead authors of this project. The results of these trials open the door for treatment in a group of patients who had previously been excluded from migraine prophylaxis trials because they were considered too highly disabled and resistant to treatment.

Dr. Black is chief of neurology and codirector of the neuroscience center at Baylor University Medical Center at Dallas. He has no relevant disclosures to report.