erm... if you mean JBPatch. erm... I think so yeah. but a full restart might not hurt.
I kind of remember that being correct though. so... undecided.
I forget exactly at what point it checks for / caches the keys, doubtless that info is on the JBPatch thread.
If in doubt. restart. That's my policy. then test by opening an app.
That should work.
*IF* you are feeling adventurous:
remove the tweak, full restart, apply the tweak, restart framework, then try opening app.
if it fails you have your answer.
if you post that detail here (or on the relevant thread) then we will all know for next time