Fremanezumab and Non-High-Dose Galcanezumab for Comorbid Cluster Headache in Patients with Migraine: Three Cases

Round 1

Reviewer 1 Report

The first question the Authors should ask is whether it is co-occurence or comorbidity. After if the pathophysiology of the two forms of primary headache may have overlaps. Then whether there is other literature in the use in optimal doses of galcanenzumab (300 mg) or subliminal (120) for cluster headache and for fremanezumab or other CGRP(r) MoABs. Then if there are RCTs on Clinical trials.gov that are exploring these opportunities for cluster headache. Finally why Galcanenzumab was approved by FDA and not EMA for prevention of CH.

Below are some suggestions for responses:

PMID: 34091819

PMID: 36447146

PMID: 36209047

PMID: 32046655

https://clinicaltrials.gov/ct2/show/NCT04970355?cond=cluster+headache+erenumab&draw=2&rank=1

Author Response

Reviewer 1

The first question the Authors should ask is whether it is co-occurence or comorbidity.

->Thank you for your important suggestion. They are comorbidities. We clearly described them in the case presentation section.

After if the pathophysiology of the two forms of primary headache may have overlaps.

->We wrote the possibility of the overlap between migraine and cluster headaches in the introduction and discussion sections.

Then whether there is other literature in the use in optimal doses of galcanenzumab (300 mg) or subliminal (120) for cluster headache and for fremanezumab or other CGRP(r) MoABs.

Then if there are RCTs on Clinical trials.gov that are exploring these opportunities for cluster headache. Finally why Galcanenzumab was approved by FDA and not EMA for prevention of CH.

Below are some suggestions for responses:

PMID: 34091819

PMID: 36447146

PMID: 36209047

PMID: 32046655

https://clinicaltrials.gov/ct2/show/NCT04970355?cond=cluster+headache+erenumab&draw=2&rank=1

->Thank you for your instruction of the articles. We referred your suggested articles and rewrote the discussion section.

Reviewer 2 Report

a collection of 3 interesting cases.
it could of some interest for the readers
i like the way the Discussion section is constructed
good comparisons, some mechanistic suggested
However, the Introduction lack at least one more paragraph into the specificity of the selected 3 cases - why - what is the commune ground
It is acceptable even to move here some aspects from the Discussion section
Conclusions are well balanced and ok. Still, the last paragraph stating further efforts is more Discussion material and should be deleted from the Conclusions. It is a general rule to focus on what you did found in this section and not what is should be done in the future. that is for discussion, as I said.

Author Response

Reviewer 2

it could of some interest for the readers
i like the way the Discussion section is constructed
good comparisons, some mechanistic suggested

->Thank you for your kind review and comments.

However, the Introduction lack at least one more paragraph into the specificity of the selected 3 cases - why - what is the commune ground It is acceptable even to move here some aspects from the Discussion section

->Thank you for your constructive suggestion. We rewrote the introduction to clearly state that the common pathophysiology may exist among CH and migraine.

Conclusions are well balanced and ok. Still, the last paragraph stating further efforts is more Discussion material and should be deleted from the Conclusions. It is a general rule to focus on what you did found in this section and not what is should be done in the future. that is for discussion, as I said.

->We deleted the discussion materials from the conclusion section as follows;

We report 3 cases of migraines without aura and comorbid CH successfully treated by fremanezumab or non-high-dose galcanezumab for CH attack prevention. We aimed to treat the migraine and consequently treated the cluster headache as well. The frequency and intensity of CH were improved by CGRP-mABs.