Page 83 - The clinical aspects and management of chronic migraine Judith Anne Pijpers
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Withdrawal and botulinum toxin A: a double blind RCT
trial, such patients were included as, in clinical practice, daily headaches and comorbid depression are common features of patients with chronic migraine. The inclusion of these difficult-to-treat patients certainly makes our study population more representative for the general chronic migraine population, but may also have contributed to lower response rates for BTA (-5.6 headache days from a baseline of 21.7 = 26%) and placebo (4.4. headache days from a baseline of 21 days = 21%). Likewise, in the PREEMPT studies, exclusion of patients with daily headaches and/or comorbid depression might have contributed to higher response rates for BTA but also placebo. In fact, placebo response rate in the PREEMPT studies was remarkably high (-6.6 headache days per 4 weeks from a baseline of 19 days = 35%) as empathized by authoritative reports such as from the British National Institute for Health and Care Excellence44 and from the European Headache Federation.45 As a result, the therapeutic gain in the PREEMPT studies of BTA over placebo was only modest: − 8.4 versus -6.6 headache days, i.e. less than two days gain per 4 weeks.23
Comparison with recent trials testing anti CGRP (receptor) antibodies in chronic migraine is similarly complicated by remarkable differences in study design, inclusion and exclusion criteria, and even definitions for primary and secondary endpoints. Placebo response rates for the primary endpoints in these trials were considerably lower compared to the PREEMPT trials: -4.6 monthly headache days (versus 12.8 at baseline = 36%) for Fremanezumab versus -2.5 headache days for placebo (versus 13.3 at baseline = 19%);37 -6.6 monthly migraine days for Erenumab (versus 17.9 at baseline = 37 %) versus -4.2 for placebo (versus 17.8 at baseline = 24%);38 -4.8 monthly migraine days (versus 19.2 at baseline = 25%) for Galcanezumab versus -2.7 migraine headache days for placebo (versus 19.6 at baseline = 14%).41 In the last two trials, patients with daily headaches were excluded.
Our study was triggered by the controversy whether or not BTA is superior to withdrawal and might save patients from experiencing acute withdrawal symptoms.1,2,7,15–17,24,25 Direct double-blind placebo-controlled comparison for all (over)used medications versus withdrawal is technically impossible. Therefore, we assessed whether add-on therapy BTA would enhance efficacy of acute withdrawal and improve quality of life during withdrawal. However, we failed to find any evidence for additional benefit from BTA on the primary (Figure 2) or any of secondary endpoints (Table 2 / Figure 3). Insufficient study
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