Conference Coverage

Pooled Analysis Clarifies VNS Efficacy in Cluster Headache

Treatment efficacy appears to vary by headache frequency.


 

BOSTON—Noninvasive vagal nerve stimulation (VNS) is well tolerated and effectively aborts episodic cluster headache attacks, according to a pooled analysis described at the 59th Annual Scientific Meeting of the American Headache Society. The treatment does not effectively abort attacks in chronic cluster headache, however.

Eric Liebler

Previous research had indicated that VNS is an effective preventive treatment for chronic cluster headache, and the results of the current analysis were unexpected, said Eric Liebler, Vice President of Scientific, Medical, and Governmental Affairs at ElectroCore Medical in Basking Ridge, New Jersey. VNS likely works through central and peripheral mechanisms, but may affect the peripheral nervous system more immediately. A chronic cluster headache attack may entail “overwhelming central sensitization,” said Mr. Liebler.

A Pooled Analysis of Two Trials

He and his colleagues studied ElectroCore's gammaCore noninvasive VNS device as an acute treatment of cluster headache in the double-blind, randomized, controlled ACT1 and ACT2 trials. Each trial included more than 100 patients with episodic or chronic cluster headache. The two studies took place at 20 centers in the United States and nine centers in the United Kingdom and Europe.

Treatment was delivered on the patient's right side in ACT1, and on the side ipsilateral to the attack in ACT2. In ACT1, patients were allowed three stimulations, or a total of six minutes of treatment per attack. In ACT2, patients were permitted as many as six stimulations, representing 12 minutes of treatment per attack. In ACT1, the primary end point was response rate (ie, the proportion of patients who achieved pain relief at 15 minutes). The primary end point in ACT2 was pain freedom at 15 minutes, and a secondary end point was the 50% responder rate (ie, mild or no pain) at 15 minutes.

Each study was underpowered for an analysis of results according to headache frequency, so the investigators performed a pooled analysis of the two studies. This examination included a fixed-effects meta-analysis and a first-order interaction test between the treatment group and the cluster headache subgroup to determine whether the magnitude of treatment effect varied significantly by cluster headache subtype.

In all, 253 patients were included in the pooled analysis, 131 of whom had episodic cluster headache, and 122 of whom had chronic cluster headache. Patients' mean age was 46.6. Approximately 21% of patients were female, 2.4% were Asian, and 4.7% were black.

Efficacy in Episodic, But Not Chronic Cluster Headache

Among patients with episodic cluster headache, the rate of pain freedom for all treated attacks at 15 minutes was significantly higher with VNS than with sham (15% vs 6% in ACT1, 35% vs 7% in ACT2, and 24% vs 7% in the pooled analysis). Among patients with chronic cluster headache, the researchers did not find significant differences in this end point between treatment groups (5% vs 14% in ACT1, 7% vs 9% in ACT2, and 7% vs 11% in the pooled analysis).

For patients with episodic cluster headache, the 50% responder rate was 34% in ACT1, 64% in ACT2, and 42% in the pooled analysis. For patients with chronic cluster headache, the responder rates were 13.6% in ACT1, 29.4% in ACT2, and 23.2% in the pooled analysis. For the proportion of attacks that became pain free, the interaction test was significant for ACT1 and the pooled analysis, but it was not significant for ACT2. For the 50% responder end point, the interaction test was significant for ACT1, ACT2, and the pooled analysis.

In April 2017, the FDA cleared the gammaCore device for the acute treatment of pain associated with episodic cluster headache in adults. The device is now available in the US, said Mr. Liebler.

“We are going to continue to examine the mechanism of action [of noninvasive VNS] and the reasons for possible [treatment] failure in chronic cluster headache,” said Mr. Liebler. These investigations could provide further clinical insight and clarify the pathogenesis of cluster headache, he added.

—Erik Greb

Suggested Reading

Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317-1332.

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