Thread by @beth_morton

Two weeks ago, I posted the #MigraineChatAMA topic: #CGRP preventives. You had great questions. Some I couldn’t answer satisfactorily, others too big to summarize adequately in a thread (i.e., I’ve give an example study for one CGRP, but other research exists). /1

Quick notes: This is not medical advice, just meant to get you pointed in the direction of things to discuss with your doctor. Also, due to space, terms are defined then abbreviations used. Studies may not use brand names (e.g., erenumab, not Aimovig). #MigraineChatAMA /2

Is it worth ⬆️ Aimovig from 70mg to 140mg if you’ve seen severity ⬇️ but not frequency?

This Q is a little tough to answer because so many of the original studies looked at reduction in monthly migraine days (MMDs) as their main outcome (freq, not severity). #MigraineChatAMA /3

That said, there is a bit of data comparing the doses. Results below are from four clinical trials showed differences in the 70mg v 140mg dose. jamanetwork.com/journals/jaman… #MigraineChatAMA /4

In ppl w/episodic migraine (EM) w/aura mean ⬇️ from baseline in MMDs at wk 12 were –1.1 for 70 mg and –0.9 for 140 mg, compared with placebo. In patients w/chronic migraine (CM) /aura, mean ⬇️ in MMDs from baseline were –2.1 for 70 mg and –3.1 for 140 mg. #MigraineChatAMA /5

Do preventive CGRPs work with rebound/medication overuse headache (MOH)/medication adaptation headache? Yes, not only MOH, but they work in people for whom previous preventives failed. #MigraineChatAMA /6

In people w/prior treatment failures: 140 mg of erenumab showed a greater ⬇️ in MMDs than the 70 mg monthly dose, both in EM and CM (w/ or w/o MOH). …alofheadacheandpain.biomedcentral.com/articles/10.11… #MigraineChatAMA /7

Study on eptinezumab in people with prior failed treatments: The difference from placebo in change in MMDs from baseline was significant with 100 mg (-2.7 days) and 300 mg (-3.2 days). pubmed.ncbi.nlm.nih.gov/35716692/ #MigraineChatAMA /8

Ppl w/MOH: CGRP mAbs are as effective in CM patients w/MOH as in those w/out & can help ppl stop use of rebound-causing meds. The ⬇️ in MMDs & acute med days/month was seen regardless of if patients stop using the acute med or not. pubmed.ncbi.nlm.nih.gov/34620085/ #MigraineChatAMA /9

What happens if you stop a preventive CGRP? In a small study, stopping was associated w/a progressive worsening of migraine over time. For most ppl, benefit of the mAb was significantly ⬇️4 mos after last injection.
journals.sagepub.com/doi/10.1177/03… #MigraineChatAMA /10

Restarting can help and evidence shows most get back to where they were before the break. …alofheadacheandpain.biomedcentral.com/articles/10.11… #MigraineChatAMA /11

Sometimes stopping happens d/t access barriers, e.g., insurance might require a break. Anecdotally, some in #MigraineChat didn’t feel the CGRP was as effective after restarting. Ask your doc what to do in the event you have a disruption in your CGRP tx sched. #MigraineChatAMA /12

Have side effects (SEs) been updated?

There is evidence that real-world use of CGRPs showed more SEs than those reported in clinical trials. This study used an 18-item checklist to look (retrospectively) at reported SEs.
practicalpainmanagement.com/pain/headache/… #MigraineChatAMA /13

.@doclarryrobbins: ⬆️ adverse events (AEs) pop up in real-world use bc of how trials measure them. Trials aren’t designed to measure AEs as outcomes, in the real-world ppl may have more severe migraine, & AEs tend to be underreported. mdedge.com/neurology/arti… #MigraineChatAMA /14

Why do some people have ⬆️ migraine attacks/symptoms on a CGRP preventive? I couldn’t find an answer but this has come up in #MigraineChat and I know some real-world studies have shown this happens. If anyone knows the “why,” please reply with resources. #MigraineChatAMA /15

Why are some non-responders? The best I can find is: we don’t know all the mechanism that lead to a migraine attack. For some, CGRP might be the main mechanism; therefore, anti CGRP mAbs work well. Other drugs are being studied that focus on diff mechanism. #MigraineChatAMA /16

This relates to the next Q: Not doing well on one CGRP (or as well as you’d like) or your insurance making you switch? Wondering how the CGRPs compared head-to-head on effectiveness and side effects? The short answer is that it’s hard to know without trying. #MigraineChatAMA /17

In aggregate, though, yes! It might be worth switching, esp if you don’t have daily attacks. Some of the mAbs work differently from each other (some attack CGRP, others the receptor) and preventive gepants work differently, too. #MigraineChatAMA /18

From erenumab to another mAb: 32% had a >= 30% reduction in MMDs. MMDs were ⬇️ by 3 days at monththree. Unfortunately, no patient with daily headache (n = 9) responded to the treatment switch. ncbi.nlm.nih.gov/pmc/articles/P… #MigraineChatAMA /19

There isn’t much head-to-head comparison of side effects, so that part is hard to answer. Best I can suggest is scroll back up to the tweet on side effects.
More on switching:
ajmc.com/view/debating-… #MigraineChatAMA /20

Can we take a mAb and gepant (specifically a preventive in each class)? There isn’t a lot of safety data on this. Most is anecdotal, small studies or case studies. First, the chance of interactions is low. #MigraineChatAMA /21

Adding a gepant can “mop up” CGRP that doesn’t get addressed by the mAb, it might also work on receptors “more readily available” to gepants. The biggest issue might be getting insurance to PAY for both. #MigraineChatAMA /22

That said, it can also increase the chance of short- and long-term side effects. CGRP has beneficial roles in other part of the body, like the cardiovascular and GI system. So we really need more data. tandfonline.com/doi/full/10.10… #MigraineChatAMA /23

If a preventive CGRP (mAb) didn’t work, will an acute? I didn’t find any studies of gepant effectiveness in mAb non responders. (If others find them, please reply). I’d point to the tweet ⬆️ suggesting the gepants might be able to work on different receptors. #MigraineChatAMA /25

Regardless, one benefit is if the CGRP mAbs caused you side effects, the gepants have a shorter half-life meaning your body clears them faster. So side effects will resolve quicker, too (compared to mAbs). #MigraineChatAMA /25

What about combining CGRP with Botox? Yes, mounting evidence suggests there is an additive and synergistic effect of the two treatments, with low likelihood of interaction. Again, getting insurance to cover both may be the hard part.
…adachejournal.onlinelibrary.wiley.com/doi/full/10.11… #MigraineChatAMA /26

More studies:
- pubmed.ncbi.nlm.nih.gov/36006191/
- …adachejournal.onlinelibrary.wiley.com/doi/10.1111/he… [paywalled]
#MigraineChatAMA /27

Do most ppl take CGRPs w/another med? I don’t have stats on the # of ppl who use a CGRP mAb or gepant, plus another migraine treatment, but there’s evidence “polytherapy may… promote a synergistic effect by acting on different pathophysiologic mechanisms.” #MigraineChatAMA /28

This article by @cynarmandmd & @ashleyalexmd goes into great detail on polytherapy (using mult migraine meds from diff classes): pros, cons, other considerations. practicalneurology.com/articles/2022-…
#MigraineChatAMA /29

Can you stop other meds if CGRP is working well? I didn’t find data, but yes. I’d weigh (w/my doc) how well the med I had been on was working for various symptoms, any SEs, etc. against the same for the CGRP. #MigraineChatAMA /30

If I felt like the CGRP was doing more with fewer SEs, taking a break from the older treatment is reasonable. #MigraineChatAMA /31

Dr. Robbins’ blog post answers most of these Qs & more, so I’m going to share this link. It is a bit outdated as some of the treatments he discusses have come out already (gepants) and some of the data I shared is newer.
chicagoheadacheclinic.com/cgrp-questions… #MigraineChatAMA /32

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I should also add the disclaimer that mistakes are mine. Let me know if see any and I'll clarify.

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