Stopping Onabotulinum Treatment after the First Two Cycles Might Not Be Justified: Results of a Real-life Monocentric Prospective Study in Chronic Migraine

Abstract

Introduction Onabotulinum toxin A (OnabotA) cyclic treatment is approved for the prophylactic treatment of chronic migraine (CM), a highly disabling disorder. Although treatment response varies among patients, current guidelines suggest to stop treatment after cycle 2 if no response is achieved. This prospective study aimed to define, in real-life setting, the evolution of the response to OnabotA over five cycles of treatment among patients non-responding to cycle 1. The results of this study might help in decision-making, in particular whether prosecuting OnabotA further or not, when facing a patient not responding to cycle 1. Methods Patients failing to respond at cycle 1 were recruited to complete five cycles. Key outcomes were: (i) a ≥50% reduction in headache days, (ii) a ≥50% reduction in total cumulative hours of headache on headache days and (iii) a ≥5-point improvement in Headache Impact Test-6 (HIT-6) scores. Results Overall, 56 patients were included. Mean age was 45.7 years (female 83.9%). Severe (≥60) HIT-6 score was reported at baseline by 95.8% of patients. Responders (headache days reduction of more than 50%) progressively increased cycle after cycle, doubling from cycle 2 to cycle 5 (from 27 to 48%). In addition, patients regressed from CM to episodic migraine moving on with each cycle, with 78% of them reaching less than nine migraine days/month after cycle 5. The headache days per month decreased significantly from cycle 1 to cycle 5 (overall from 23.3 ± 5.7 to 9.2 ± 3.6; p < 0.001). During 12 months (5 cycles), migraine days per month progressively abated (from 18.5 to 8.7; p < 0.001), days with symptomatic medications intake/month consistently decreased (from 17.4 to 8.1; p < 0.001), and mean HIT-6 score lowered (from 72.4 ± 5.7 to 50.2 ± 4.3; p < 0.001). Conclusion The positive effect of OnabotA treatment spreads over the course of the treatment and might also manifest late in treatment course among patients with no benefit after the first two cycles. Thus, the results of this real-life study suggest to extend OnabotA treatment further, beyond cycle 2, to avoid premature withdrawal in patients who would have become responders at cycle 3, 4, or 5.

OnabotulinumtoxinA: A Review in the Prevention of Chronic Migraine

“…3.3 ). In addition, a small real-world from Europe [ 80 ] has reported a delayed and progressively beneficial effect among patients who continue to receive treatment after failing to respond to the first cycle; this supports the notion that at least another one to two cycles should be attempted before deeming those individuals who do not respond initially to be nonresponders [ 81 ].…”

Real world preventative drug management of migraine among Spanish neurologists

“…Spanish experts recommendations for the use of OnabotA stated that the first procedure should be performed according to the PREEMPT paradigm, administering 155 Units and in case of lack of response, dose could be increased up to 195 Units in the first three procedures [19]. We found that in certain cases, neurologists admitted to using lesser or higher doses.…”

Onabotulinumtoxin‐A in Chronic Migraine: Should Timing and Definition of Non‐Responder Status Be Revised? Suggestions From a Real‐Life Italian Multicenter Experience

“…To date, some real‐life studies addressed the evolution of CM patients undergoing only 2 OBT‐A sessions instead of one‐year treatment. A monocentric real‐life study by Sarchielli et al reported the evolution in response to OBT‐A repeated cycles among 56 patients non‐responding to cycle 1. The authors demonstrated that Responders (they considered 50% of reduction in headache frequency) progressively increased cycle after cycle (up to 5) and concluded that clinicians should prosecute OBT‐A to guarantee an effective therapeutic option.…”