CGRP and migraine 3: mAbs 2019

In the last blog, I told the story of the development of monoclonal antibodies (mAbs) against CGRP, from their first appearance in the literature in 2007 to their licensing in the USA and Europe in 2018-19. In the third blog in this sequence I will go into a little more detail on the evidence for the effectiveness of the mAbs, their safety and side effect profiles, and where we stand at present on their use in the United Kingdom.

The CGRP mAbs have been subjected to clinical trials in patients with both episodic migraine (that is, with headaches on 4-14/days month) and chronic migraine (≥15 days/month). In episodic migraine the mAbs on average reduced migraine frequency by 4-6 days/month (vs 2-3 days/month for the placebo). This doesn’t sound like a huge difference, but it equates to a ≥50% reduction in migraines in 30-40% of patients, which is enough to significantly improve migraine sufferers’ quality of life.

In the chronic migraine trials, ≥50% reduction in migraine days was seen in 40% of patients on erenumab (vs 23% on placebo), 41% of those on fremanezumab (vs 18% placebo), and 28% of those on galcanezumab (vs 16% on placebo). The ‘therapeutic gain’ of these drugs over placebo of 12-23% is comparable to, or better than Botox (12%) and clearly better than topiramate (10%).

Real world experience of prescribing erenumab (Aimovig) over the last 12 months suggests that these trial results reflect what we see in clinical practice. Of the 40 patients I treated between September 2018 and June 2019, 9 had a ≥75% reduction in their migraines, 10 had a 50-75% reduction, and only 6 had a 0-25% reduction. Some of the patients who had responded really well had previously failed to benefit from numerous oral preventive medications, and Botox.

CGRP antibodies have shown an excellent safety profile in clinical trials of >2500 patients, and have proved to be very well tolerated. The commonest side effects (of erenumab, at least as seen in my patients) seem to be pharyngitis and constipation. Safety and tolerability seem to be maintained over the medium term, at least as evidenced by data from open label extension studies which now run to ≥5 years. So far, there has been nothing to suggest an increased risk of cardiovascular problems in patients taking CGRP mAbs. There is now one case of a 41 year old woman suffering a thalamic stroke in close temporal association to the administration of erenumab, though a causal relationship between the treatment and the stroke is not certain.

Overall, therefore, the CGRP mAbs represent significant additions to our options for treating people with the more severe forms of migraine. The major logistical hurdle for most people at the moment is the cost of obtaining them privately. It is vital that we, as a headache community, campaign for the approval of at least one of drugs for use on the NHS in England, Wales, and Northern Ireland. Erenumab is already approved for use in chronic migraine in Scotland.