Miriam E. Tucker

June 29, 2015

Washington, DC — A novel investigational implanted nerve stimulator device continues to alleviate pain at 2 years in two thirds of patients with refractory cluster headache, new data suggest.

The latest findings for the approach — including completed 2-year data, use of preventive medication, disability, and quality-of-life measures — were presented at the American Headache Society (AHS) 57th Annual Scientific Meeting by Jose Miguel Lainez, MD, PhD, from University Clinic Hospital, Catholic University of Valencia, Spain.

The ATI Neurostimulation System (Autonomic Technologies Inc) is CE marked in Europe and is in clinical trials in the United States. The device is inserted transorally into the maxilla using a minimally invasive approach, targeting the sphenopalatine ganglion (SPG). The patient activates the system on-demand via a handheld wireless remote controller held on the cheek above the implanted device.

"In the long-term it's very comfortable for the patient…I think the data are good because we're talking about a very refractory population," Dr Lainez told Medscape Medical News. "In some patients it stopped the attacks and in some it reduced the number of attacks."

In an interview, session moderator Robert Shapiro, MD, PhD, professor in the Department of Neurological Sciences at the University of Vermont, Burlington, said, "Cluster headache is more prevalent than [multiple sclerosis] and probably as disabling. People think of it as a rare disorder, but it's not…. About half a million Americans are believed to have cluster headache."

Regarding the SPG stimulator device, Dr Shapiro said that it "shows early evidence of being able to suppress attacks. It's not a cure, but [cluster headache] is a disease that has never had a drug developed for it.…To have a drug or device specific for it is dramatic and really welcome."

Sustained Relief

In an initial randomized, sham-controlled 8-week study published in 2013, 19 of 28 (68%) patients with refractory cluster headaches achieved an acute response (pain relief at 15 minutes in at least 50% of at least five treated attacks), a frequency (preventive) response (at least 50% reduction in attack frequency from baseline during the study period with no change in medications), or both, as compared to just 7% of the sham-treated patients.

At the American Academy of Neurology meeting in May 2015, Dr Lainez presented data on acute response to SPG stimulation therapy during long-term follow-up, which began 12 to 15 months after insertion of the device. In 33 patients with a total of 5132 cluster headache attacks, SPG stimulation was an effective therapy for 65% (3354) of treated attacks.

Now, with all 33 of those patients having completed 2 years, 20 patients were responders, with 15 achieving acute response and 11 achieving preventive response (6 had both). A total of 5956 attacks were treated among all 33 patients (19% mild initial pain, 45% moderate, 23% severe, 13% very severe).

Of approximately 4000 attacks among the acute responders, the stimulator was effective in treating 78%. Among the frequency responders, the device reduced the frequency of attacks by 83%.

Of the 21 patients who were responders at 18 months, 3 became nonresponders by 2 years. However, 2 of the 12 nonresponders at 18 months became responders by 2 years. In all, 86% of therapeutic responders — including both acute and preventive — maintained their response at 2 years, Dr Lainez said.

At 2 years, headache disability, as assessed by the Headache Impact Test-6, showed improvement in 60% of patients and quality of life, assessed by the 36-Item Short-Form Health Survey version 2.0, was improved in 73%.

Use of preventive medications was reduced in 61% (20 patients), including 9 patients who were able to stop all of their headache medications during the study.

In an analysis of those 9 patients presented separately in a poster at the AHS meeting, Dr Lainez reported that pain-free periods began 150 days into the study and lasted an average of 111 days.

Patients achieved pain relief or freedom in 50.7% (77 of 152) and 57.3% (110 of 192) of evaluable attacks before and after remission, respectively. After remission, 5 patients stopped use of acute medications and 4 had clinically significant reductions in their number or dose of preventive medications or remained off these medications.

Dr Shapiro told Medscape Medical News that he was heartened by both these data for SPG stimulation and Eli Lilly's pursuit of a cluster headache indication for their investigational calcitonin gene-related peptide (CGRP) monoclonal antibody in addition to migraine, noting "This is so different [from the past] that anybody is studying drugs or devices for cluster headache…It's a different disease from migraine."

Dr Lainez has received grants or research support or has been an advisor or on speaker' bureaus for ATI, Allergan, Boehringer Ingelheim, Electrocore, Lilly, Lupin, Medtronic, Novartis, Otsuka, Roche, and Teva. Dr Shapiro serves on the independent data safety monitoring board for the Lilly anti-CGRP drug trials.

American Headache Society (AHS) 57th Annual Scientific Meeting. Abstracts OR10 and PF36. Presented June 20, 2015.


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