Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study

DOI: https://doi.org/10.1007/s40122-021-00253-0

Abstract-Summary All the centers provided data on patients treated with BT-A for CM over the first three cycles of treatment.

For each treatment cycle we defined patients as “good responders” if reporting a ≥50% reduction in monthly headache days compared with the three months before starting BT-A, “partial responders” if reporting a 30–49% reduction in monthly headache days, and “non-responders” if reporting a < 30% reduction in monthly headache days or stopping the treatment before the third cycle.

Seven hundred and eighty-four (64.6%) of the 1213 patients reporting a good response during the first and/or the second cycle had a good response during the third cycle; 309 (49.3%) of the 627 patients reporting a partial response (but no good response) during the first and/or the second cycle had a good response during the third cycle; only 65 (6.3%) of the 1039 patients who did not respond during both the first two cycles achieved a good response during the third cycle.

Our data suggest that patients with CM responding to BT-A during the first two cycles will likely benefit from the third cycle of treatment, while the probability that non-responders to the first two cycles start responding during the third cycle is low. These results can help guide the individual decision to stop or continue treatment

after the second cycle in patients who have not responded to the first two cycles.

Extended: Our data suggest that (1) patients showing early response to BT-A tend to maintain their response; (2) a relevant proportion of patients showing even partial response to BT-A during the first two cycles of treatment will become good responders during the third cycle; and 3) the probability of good clinical response to BT-A is lower in patients not responding during both the first two cycles.

Our data suggest that we should wait for a 30% reduction in monthly headache days over the first two treatment cycles to determine the efficacy of BT-A. Many patients with CM continue treatment with BT-A because of a decrease in headache duration and/or intensity, even in the absence of a decrease in monthly headache days, as they still perceive a benefit.

Future personalized approaches to treatment, including pharmacogenetics [304, 305], will likely provide an objective basis for the prediction of response to BT-A as well as to other migraine preventive treatments.

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4 Treatment

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Introduction Many patients report a favorable response to BT-A treatment during the first cycle of treatment with BT-A, whereas other patients who do not report any meaningful improvement during the first cycle start responding to the treatment during the sec- ond or third cycle.

The National Institute for Health and Care Excellence (NICE) UK guidance for the use of BT-A in CM recommends discontinuing the treatment after two cycles if patients do not reach at least 30% reduction in headache days [306].

For those reasons, providing reliable estimates of the onset and the early evolu- tion of response to BT-A might help avoid prolonged ineffective treatment and favor patient compliance.

In order to improve the management of patients with CM who start BT-A treat- ment, we aimed to provide data to clarify how the clinical response develops and evolves over the first three treatment cycles.

Methods We performed a retrospective analysis of prospectively collected data from European centers treating CM with BT-A.  All the centers met the following inclusion cri- teria: 1.

Having already performed a real-life prospective data collection on patients with CM, diagnosed according to the International Classification of Headache Disorders (ICHD) criteria, aged ≥18 years, treated with BT-A 155–195 units quarterly accord- ing to the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol [149] 2.

Good responders patients achieving a ≥50% reduction in headache days from baseline—i.e. the 3  months prior to BT-A treatment initiation—to the respective 3-month cycle 2.

The non-responder group also included patients lost to follow-up or discontinu-

ing treatment before the third cycle.

We performed the main analyses on the whole data set, comparing the character- istics of good responders at the third BT-A cycles with those of partial or non-responders.

Results Of the 1213 patients reporting a good response during the first and/or the second cycle, 784 (64.6%) reported a good response and 109 (9.0%) a partial response dur- ing the third cycle; notably, of the 507 patients who were good responders during both the first and second cycle, 389 (76.7%) maintained the good responder status during the third cycle.

A partial response during either the first or the second cycle, without a good response during the first two cycles, was attained by 627 patients, 309 of whom (49.3%) had a good response and 130 (20.7%) a partial response during the third cycle.

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Sixty-five (11.5%) of the 565 patients maintaining the non-responder status dur- ing both the first two cycles achieved a good response during the third cycle, while 98 (17.3%) had a partial response.

Discussion Our findings suggest that it is not reasonable to discontinue the treatment with BT-A after only one cycle, otherwise a relevant proportion of patients may miss a valid therapeutic opportunity; in our study, 532 (33.8%) of the 1571 non-responders dur- ing the first cycle achieved a good or partial response during the second cycle, while 590 (37.6%) achieved a good or partial response during the third cycle.

Considering the findings of this study, continuing BT-A treatment is advisable in patients reporting even a partial response within the second cycle, while stopping treatment might be considered in patients who are non-responders during the first two treatment cycles, because the probability of a later response is low.

Conclusion According to our data, the first two treatment cycles of BT-A can help determine the response to the drug during the third cycle in patients with CM.

Patients reporting at least a 30% decrease in monthly headache days within the first two cycles compared with baseline are likely to respond to the third cycle of BT-A. Conversely, patients not reporting at least a partial response to the first two cycles are unlikely to respond to the subsequent cycle and might be considered for treatment discontinuation.

We think that our study can help inform clinical practice.

Acknowledgement A machine generated summary based on the work of Ornello, Raffaele; Ahmed, Fayyaz; Negro, Andrea; Miscio, Anna Maria; Santoro, Antonio; Alpuente, Alicia; Russo, Antonio; Silvestro, Marcello; Cevoli, Sabina; Brunelli, Nicoletta; Vernieri, Fabrizio; Grazzi, Licia; Baraldi, Carlo; Guerzoni, Simona; Andreou, Anna P.; Lambru, Giorgio; Frattale, Ilaria; Kamm, Katharina; Ruscheweyh, Ruth; Russo, Marco; Torelli, Paola; Filatova, Elena; Latysheva, Nina; Gryglas-Dworak, Anna; Straburzynski, Marcin; Butera, Calogera; Colombo, Bruno; Filippi, Massimo; Pozo-Rosich, Patricia; Martelletti, Paolo; Sacco, Simona. 2021 in Pain and Therapy.

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