An analysis of the efficacy of calcitonin gene-related peptide inhibitors on the treatment of migraine in adults

The CGRP monoclonal antibodies are the first class of medication developed specifically for migraine prevention, in contrast to previous preventative medications, that were in the anti-hypertensive, anti-epileptic and anti-depressant class. There are two notable divisions within the CGRP inhibitor class: the CGRP monoclonal antibodies (CGRP mAbs), and the small molecule CGRP antagonists (gepants). This thesis conducts a retrospective analysis of notable clinical trials such as the ACHIEVE I, ACHIEVE II, LIBERTY, ARISE, STRIVE, PREEMPT, and COMPEL studies to determine the efficacy of CGRP inhibitors. In ACHIEVE I, 38.6% of participants in the 50 mg ubrogepant group experienced pain freedom 2 hours post dose (p=0.002) and in ACHIEVE II trial in the 50 mg ubrogepant group, 21.8% reported pain freedom 2 hours. In participants that received Rimegepant at a 75mg dose, 21%of participants reported more freedom from pain at 2 hours than placebo (p<0.0001).^40 In another study, participants received placebo, 50 mg and 100 mg of sumatriptan.^43 Results of the study showed that more than half of participants, 57%, in the 100 mg Sumatriptan group and exactly half of participants in the 50 mg group had pain relief at 2 hours post-dose.^43 In the LIBERTY trial, at 12 weeks, 30% of individuals that received erenumab reported a fifty percent or more reduction in the monthly number of migraine days than individuals in the placebo group (p=0.002).^45 In the STRIVE trial, the average number of migraine days experienced by the participant at baseline was 8.3, and was assessed by the 4th month through the 6th month. This baseline decreased to 5.1 days (a 3.2 difference) in the participants that received an injection of 70 mg of erenumab (p<0.001).^46 The participants that received an injection of 140 mg erenumab, decreased from the baseline to 4.6 days of migraine (a 3.7 difference) (p<0.001) . 46 Participants that received placebo reported the least change from baseline, only a 1.8 day change (p<0.001).46 In the ARISE Trial patients receiving erenumab experienced a change of 2.9 monthly migraine days, a 1.1 increase from the reported change of 1.8 days reported by study participants for the monthly migraine days in the placebo group (p<0.001).^47 The PREEMPT1 trial did not meet statistical significance for their primary endpoint or study measure, which was to assess for a mean change in monthly mean headache episode frequency between baseline and week 24 of the trial (p=0.344)^48. Participants in the PREEMPT2 trial experienced a reduction by 9 days when compared to placebo for the primary end point, frequency of headache days per 28 days relative to baseline (p<0.001)^49. In the COMPEL study, participants experienced -10.7 day reduction in headache days by 108 weeks (p<0.0001).^50 There are several advantages to CGRP mAbs. Patients are more likely to adhere to CGRP mAbs medication and tolerate this medication than other medication options^17, CGRP mAbs do not give rise to toxicity in the liver because these medications do not interact with the liver^17, and CGRP mAbs have a long duration in the human body as they have a half-life of 20 to 30 days which provides patients with the opportunity to not take the medication as frequently.^51 Another reason why CGRP mAbs are advantageous compared to traditional treatment options is that they have a strong affinity and specificity for the CGRP receptor or CGRP molecule. This high specificity prevents the medication from causing undesirable effects on other receptors^51