Lawrence Robbins, M.D.
NOTE: Data was collected from Oct. 2018 through May, 2019. Data was collected by Dr. Robbins and Brook Phenicie, NP-C. This was a de-identified retrospective study. IRB was obtained This write-up is preliminary.
All patients had the diagnosis of chronic migraine. Almost all patients had utilized Botox for their chronic migraine. Each patient had utilized at least 3 preventive medications in the past. Many of these patients remained on a daily preventive. Approximately 60% of the patients were considered to have refractory chronic migraine (European Headache Federation definition). The primary data point was the degree of relief obtained during the initial 3 months. Relief was determined by: the percentage decrease (versus baseline) in the number of migraine days, combined with the number of moderate or severe headache days (even without features of migraine).
Moderate or severe days were assessed via a 10-point VAS. Relief was averaged for the entire first 3 months. If patients discontinued the mAb prior to completing 3 months of treatment, relief was considered to be 0%. Consents were obtained.
Ajovy: Efficacy After 3 Months
0 to 30% relief: 50% of patients
31 to 70% relief: 33%
71 to 100% relief: 18%
Subset: Combined (31 to 100% relief): 51%
Subset: Patients with 95 to 100% relief: 8%
Ajovy: Side Effects
Nausea: 6% Constipation: 6% Depression: 6%
Increased headache: 5% Muscle pain and/or cramps: 5%
Rash: 4% Joint pain: 4% Anxiety: 4% Fatigue/tiredness: 4%
Weight gain: 4% Injections site reactions: 3% Irritability: 3% Alopecia: 3% Diarrhea: 1% Weight loss: 1% Shingles(recurrent): 1%
Emgality: Efficacy after 3 months
0 to 30% relief: 40%
31 to 70% relief: 46%
71 to 100% relief: 14%
Subset: Combined (31 to 100% relief): 60%
Patients with 95 to 100% relief: 3%
Emgality Side Effects
Constipation: 10% Depression: 6% Increased Headache: 6%
Fatigue/tiredness: 4% Nausea: 4% Injection site reaction: 4%
Weight gain: 3% Alopecia: 3% Muscle pain and/or cramps:3%
Anxiety: 3% Rash: 3% Insomnia: 1% Weight Loss: 1%
Efficacy: The efficacy for Ajovy and Emgality is reasonable (50 to 60% of patients report at least a 31% improvement over the first 3 months). The difference in efficacy between Ajovy and Emgality is probably not significant. Ajovy was frequently prescribed for those who had failed on Aimovig (during October and November, 2018), and this may have artificially lowered the Ajovy results. This efficacy is similar to what we reported for Aimovig (we found that 58% of those on Aimovig achieved at least a 31% improvement). This efficacy is similar to what is generally reported with the use of Botox. As is the case with Botox, there is a small percentage of patients who do extremely well (95 to 100% improvement).
Over time, our Aimovig study indicated that some patients do find the mAb “wearing off’. This seems to happen in a small but significant minority of people. Anecdotally, we have found that Botox seems to “wear off” at a lower rate than is observed with the CGRP mAbs.
We are currently assessing the month to month effect of Ajovy and Emgality over 8 months. With Aimovig, we found that, after month 2, it was somewhat predictable what would happen over the next 4 months. We are also studying the effect of a CGRP mAb combined with Botox.
Side Effects: This is where the formal Phase 2 and 3 mAb studies are not accurate. The CGRP mAbs produce a plethora of side effects, most of which are mild. Sometimes these are transient, but often they do not diminish. As of 3/31/2019, on the FDA FAERS website, there were 12,000+ side effects reported for Aimovig, with 1,200+ serious side effects. Ajovy and Emgality had smaller numbers. In our Aimovig, Ajovy, and Emgality studies, we encountered a number of side effects that were not reported in the companies’ studies. I have used 4 sources to evaluate side effects in this class: 1. Our own patients, 2. The CGRP patients chat boards (over 16,000 patients), 3. Physician communications, and 4. The FDA FAERS website. It appears as if Aimovig may produce more side effects than Ajovy/Emgality, but this is a preliminary observation. We encountered 3 serious side effects from Aimovig; only one from Ajovy (recurrent shingles: possibly coincidence), and none due to Emgality.
It may be that the portions of the brain not protected by the blood brain barrier produce some of the central side effects. These include the hypothalamus, pituitary, area postrema, and the choroid plexus. Weight gain, anxiety, and depression may be accounted for via perturbations of the HPA axis, in which CGRP plays a prominent role. We need the FDA, with help from the companies, to update the PI. Serious side effects need to be further evaluated in a comprehensive fashion.