Health technology assessment peripheral neurostimulators of the sphenopalatine ganglion in Spain

Cluster headache (CH) is a primary headache, integrated into the group of trigeminal-autonomic headaches characterized by the appearance of attacks (grouped in series that are called clusters) of strictly unilateral and periorbital pain along with ipsilateral vegetative signs of the painful side, such as ptosis, miosis, sweating, tearing, rhinorrhoea or eyelid oedema.

Studies report an incidence of CH ranging from 2.5 to 9.8 cases/100,000 person-years and a prevalence ranging from 53 to 381 cases/100,000 persons. According to some studies, it appears to be more common in men than in women with a male-to-female ratio of 7: 1 to 3: 1

Treatment for CH should be initiated by attempting to suppress the precipitating factors of the attack, if any. Pharmacological treatment can be symptomatic treatment and directed to prophylaxis. Another therapy option indicated for refractory CCH is the surgical trigeminal section through different pathways. Recently, alternatives to this surgery have appeared, including sphenopalatine ganglion (SPG) stimulation by a small device that is inserted trans-orally, using a minimally invasive gingival buccal incision. This neurostimulation system also consists of a remote controller that the patient activates on demand and in a controlled manner by himself when he needs it. The remote controller also allows the physician to facilitate adjustment of the parameters in the neurostimulator that the patient needs.

The aim of this report was to assess the efficacy and safety of peripheral neurostimulators of the sphenopalatine ganglion in the treatment of refractory chronic cluster headache.

A systematic review (SR) of the scientific literature has been carried out. The identification of studies was made through an exhaustive search of the scientific literature in the following databases: PubMed, The Cochrane Plus, CRD, NICE, WOS, ICTRP, Clinicaltrials and EuroScan. The selection of clinical studies was done until October 31, 2016, without restrictions by clinical sample size. Clinical trials, SR or meta-analysis, HTA reports, or clinical practice guidelines, published in English, Spanish or French, studying patients with refractory CCH and undergoing SPG stimulation by the use of neurostimulators were included.

Results:

• Literature:
  • Six of the 35 references that initially met the inclusion and exclusion criteria were selected: 1 Health Technologies Assessment report from the Austrian Agency conducted with RS methodology, 1 NICE report, 1 clinical trial (Pathway CH-1), 2 articles with follow-up data of patients from the 24-month Pathway CH-1 trial and a post-marketing register that included, among others, the Pathway CH-1 trial patients
• Efficacy results:
  • Pathway CH-1 trial retrieves data from 28 of 33 patients that completed the experimental period and found the following results: Pain relief at 15 minutes after neurostimulation was achieved in 67%, 7% and 7% of full stimulation (FS) treated attacks, sub-perception stimulation (SPS) treated attacks and sham stimulation (SS) treated attacks respectively (p<0,001). Pain reduction at 30, 60 and 90 minutes after neurostimulation was achieved in 56%, 61%, and 60% of CH attacks treated with FS compared to 8%, 12%, and 13% of CH attacks treated with SS, respectively (p<0,001). Pain freedom by 15 minutes after neurostimulation was achieved in 34%, 2% and 2% of CH attacks treated with FS, SPS and SS respectively (p<0.001). Acute rescue medications were used in 31%, 78% and 77% of CH attacks treated with FS, SPS and SS respectively (p=0,0001). At the end of the experimental period, the mean CH attack frequency was reduced from 17,4 to 12,5 attacks/week (p=0,005). 68% of patients responded to treatment. With respect to quality of life, Headache Impact Test (HIT) improved in 6.8 ± 10.2 points (p=0,002), and the SF-36 scale improved in 75% of patients: 21 % in physical function, 29% in mental function. 25% of the patients improved in both functions
  • 24-month follow-up study of the 33 patients enrolled in the Pathway CH-1 trial showed that: 50% of the treated attacks become pain free; 45% of the patients was acute responder, 35% was frequency responder, and 61% was both; HIT was reduced by 4,8 units compared to basal measure in 29 patients who completed this scale (p=0,0048); 69% of patients found the treatment useful. Finally, 11 patients (33%) had CCH attacks contralateral to the side of their inserted stimulator.
• Safety results:
  • Pathway CH-1 Clinical trial informed that 1 patient (3%) had to be explanted within the first 30 days after implantation, and 5 patients (16%) had to be explanted between 30 days and 1 year after implantation. The study reported a total of 128 adverse events in 32 patients- The most frequent adverse event was sensory disturbances that occurred in 81% of the patients within the first 30 days after implantation of the device, being resolved in 58%; and in 16% of patients between 30 days and 1 year after the procedure, being resolved in 60% of the patients
  • The registry that included 99 patients reported that 29/32 patients from the Pathway CH-1 completed a self-assessment questionnaire 18 months after the implant. 86% of patients considered that the effects of surgery were tolerable and 90% indicated that they would make the same decision again to treat their CH
• Economic results:
  • No cost of the device or cost-effectiveness studies have been found that compares different therapeutic alternatives in CCH

Conclusions:

• The information collected in studies evaluating the treatment of SPG stimulation for CCH comes mainly from a single small, short-term clinical trial.
• Regarding efficacy, positive results following SPG stimulation in relation to pain relief, the frequency of attacks, use of medication or quality of life of patients were found. At 24 months after the intervention, some patients present favorable results from the basal situation, although the follow-up data are scarce.
• Regarding the safety of the SPG stimulation, a significant number of adverse events in the first 30 days after the intervention were found, although the majority can be resolved successfully. There are no long-term safety data for the procedure.
• Clinical studies included in the review have limitations and are not independent. Publications that compare the effectiveness of the SPG stimulation to other medical or surgical treatment have not been found.
• According to available data, most patients with CCH are satisfied with the treatment received. It is important to note that the peripheral SPG stimulation may be the only alternative treatment for non-responder patients to other treatments.
• It is considered fundamental to continue research on the safety and efficacy of the SPG stimulation in CCH. In cases where intervention may be indicated, treatment should be performed under a research protocol, paying special attention to obtain the patient’s written informed consent.
• The conditional inclusion of the GEP neurostimulator for highly selected cases due to the limited evidence available is recommended. This intervention should be carried out within a research/monitoring program that helps to generate evidence on the safety and effectiveness of the procedure and to review the decision on its possible inclusion in the NHS Common Services Portfolio.

See the full report in Spanish with a summary in English here

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