OnabotulinumtoxinA (Botox) treatment resulted in discontinuation of acute medication overuse and oral preventive therapies after 1 year in more than half of individuals with chronic migraine, researchers found.

Of 115 study patients overall, 62% of the 92 characterized as overusing the medications and almost half of the 107 receiving preventives were able to discontinue those therapies after the first year, Angel Guerrero, MD, of Hospital Clínico Universitario in Valladolid, Spain, and colleagues reported online in The Journal of Headache and Pain.

Chronic migraine remitted to episodic migraine in about two-thirds of patients, as shown in a retrospective assessment of individuals who received at least five sessions of Botox according to the PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) protocol after not responding to topiramate or another neuromodulator and a beta-blocker.
"Botox has dramatically improved migraine in many patients," Guerrero told MedPage Today via email. "The evolution from almost daily headache (chronic migraine) to less than 15 days per month (episodic migraine) -- and in many patients to less than 5 days per month -- is quite important. Unfortunately, it is not easy to discontinue treatment, as our results show."

There was also evidence of a durability of effect in the study, which saw some patients treated for more than 4 years. Following the third treatment, about one in five patients was able to delay the standard every-3-month Botox administration to the fourth or fifth month, and 10% were able to stop treatment temporarily.



Treatment was continued in patients who reported at least a 30% reduction in headache days after three procedures, and at that point responders using concurrent oral therapies began to decrease their medication use. Use of any analgesic decreased from 19 days at entry to less than 9 days per month, and triptan use decreased from 18 to 4 days per month.

About one-third of patients received additional injections up to 195 units according to the "follow the pain" protocol. Despite some initial response, 16% of patients stopped treatment due to lack of efficacy beyond the first year.
"We consider that discontinuation of acute medication overuse and oral preventive therapy as well as reduction of frequency of procedures are realistic goals in real-life, long-term using of Botox in chronic migraine patients," Guerrero and his colleagues concluded.

Asked for his perspective, Peter Goadsby, MD, PhD, of the University of California at San Francisco, who was not involved in the study, explained, "About 40% of people with chronic migraine need a preventive, and insurance companies expect people to try at least two or three [before a more expensive treatment like Botox would be approved]. It is good to see medication overuse discontinued. However, I think the proportion of patients reported here who managed to discontinue medication overuse or stop taking a preventive is probably higher than it would be in my practice, because my experience is with patients who have failed more preventives than those in this study."

In a recent update of the American Academy of Neurology guidelines, for the use of botulinum toxin in various neurological disorders, Botox received a level A recommendation in chronic migraine, although the authors noted that the magnitude of the benefit is small, as reported by MedPage Today.

The researchers noted that their findings reflect previous Botox studies showing similar reductions in migraine and headache days, and similar benefits in patients with or without analgesic overuse.

Long-term Botox treatment has also shown significant reductions in headache frequency, pain intensity, headache disability score, as well as anxiety and depressive symptoms, and an overall marked improvement in patients' quality of life.

For the study, participants were selected from prospective registers of patients at three hospital-based headache units in Spain who had started treatment with Botox for chronic migraine (defined as headache occurring on 15 or more days per month during more than 3 months, and that has the features of migraine headache on at least 8 days per month).

The study spanned a 4-year period beginning in January 2012, when Botox was licensed in Spain for use in patients with chronic migraine refractory or intolerant to standard prophylactic drugs.

Cohort sex proportions and age baseline characteristics of patients were comparable to those described in the PREEMPT trial: Of the 115 patients, 98 (85%) were female, and patients ranged in age from 14 to 74, with a mean age of 43 at study entry.

Pregnant or breast-feeding women and excessive users of alcohol were not included. However, patients with comorbidities such as anxiety, depression, or fibromyalgia and those with common vascular risk factors were included.
Participants had been diagnosed with chronic migraine for a mean of about 3.5 years (43.1 ± 38.2 months) before their first procedure, and had received previous treatment with approximately eight (7.6 ± 2.3) oral preventatives.

At first procedure, reflecting the "real-life" setting of the trial, 93% of patients were taking a concurrent oral preventative. About 80% fulfilled the criteria for medication overuse according to the International Classification of Headache Disorders (ICHD)-3beta, with half of those overusing triptans. Use of previous preventive oral medications could be continued, but the dose could not be increased.

Results were based on patient reports using a headache diary, in which patients recorded headache days; migraine days; days of use of symptomatic medication, particularly triptans; and emergency department visits due to headache. No delayed unexpected side effects of Botox have been detected, the researchers said.

Goadsby noted that while the trial is retrospective and has too few participants to assess safety, it is nice to see an open-label experience confirm that Botox is generally well tolerated, as has been shown in randomized controlled trials.