Factors associated with efficacy of occipital nerve stimulation in medically intractable chronic cluster headache

Background/Objective: Occipital nerve stimulation (ONS) has become an established therapy for medically intractable chronic cluster headache (MICCH), but unfortunately, one third of the patients do not respond satisfactorily. Reliable predictors of treatment success would help physicians improve indication for ONS in MICCH. Although a recent report suggested several factors that were associated with treatment failure (early onset of cluster headache [CH], chronic cluster headache [CCH], and smoking) this study was small, did not use a formal model, efficacy was poorly defined, and the follow-up was only of short duration. Here, we retrospectively sought: (i) reproduction of these associations and (ii) identification of possible other associations in our previously published double-blind randomized controlled “Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache” (ICON) trial, and long-term follow-up, of the efficacy of ONS in MICCH. Methods: Data from the double-blind randomized controlled ICON trial, and its prospective open-label extension, were analyzed in this prospective cohort study in the Netherlands (October 12, 2010, to December 20, 2020) for: (i) relative differences in attack frequency and (ii) subjective satisfaction with effect between baseline and at 4 and 24 weeks, and 2 and 5 years, after ONS implantation. Formal statistical models were used to: (i) verify the previously detected associations and (ii) identify possible other associations. Results: Early onset of CH and smoking did not predict efficacy of ONS. Relative reduction in attack frequency at 24 weeks (B = 0.44, 95% confidence interval [CI] 0.13–0.76; p = 0.007) and the time since onset of CCH (B = 4.04, 95% CI 1.16–6.92; p = 0.007) appeared to be the only factors that were associated with objective efficacy at 2 years, and relative attack reduction after 2 years was the only factor associated with objective efficacy at 5 years (B = 0.501, 95% CI 0.186–0.815; p = 0.003). The odds of experiencing subjective satisfaction with ONS after 2 years increased with a later debut of CCH (adjusted odds ratio [aOR] 1.06, 95% CI 1.01–1.12; p = 0.033) and greater relative reduction in attack frequency at 24 weeks (aOR 1.02, 95% CI 1.00–1.04; p = 0.017). Conclusion: In a controlled setting, early onset of CH, CCH, and smoking were not associated with treatment success of ONS for MICCH, as previously suggested by others in an uncontrolled setting. Early response at 24 weeks after initiation of ONS was the only factor that was associated with long-term efficacy, which was identified. Since a large proportion of patients with MICCH improve with ONS, we recommend offering ONS to all patients with MICCH.