Our team deals with this issue as well.

About 50% of our ticket volume is Agent created, 30% of which customers respond to. We want to include our response time to these customers, but it often results in a skewed First Response Time because of the delay that our customers take.

Here is a solution that we made!

The agent creates a ticket
The agent applies a tag of 'outbound' and submits it as any status.
I've created a trigger that looks for the 'outbound' tag and automatically sets the ticket to closed (this prevent the First Response Time for this ticket)
The trigger notifies the requester (i.e. end-user) - let's say three days pass.
The customer replies, creating a follow-up ticket.
When/if the requester (i.e. end-user) responds, a follow-up ticket is created with the 'outbound' tag on it from the previous ticket.
A trigger then removes the 'outbound' tag from the follow-up ticket and adds a 'follow-up' tag (so we can report on the number of follow-ups we get vs outbounds.)
The Agent responds and an accurate First Response Time is recorded!

Here are my screenshots of the triggers.

Thanks,

Ryan