Why four
A printed comic is made of sheets folded in half. Each sheet carries four pages: two on the front, two on the back. So an interior has to be a multiple of four, and a saddle-stitched book cannot be anything else. Perfect-bound books are built from larger signatures and the printer pads them with blanks, but most still ask for a multiple of four, and the blanks land where the printer puts them unless you place them yourself.
Which binding
Saddle stitch (staples through the fold) works up to about 48 pages on standard stock, sometimes 64 on thin paper. Past that the book will not close flat and the inner pages creep outward at the fore-edge. Perfect binding needs enough pages to make a spine that can hold glue, typically 32 or more. The tool flags both ends. The booklet imposition table shows the exact page pairs for printing double-sided and folding at home.
See how many pages should a comic have? for the story side of the question.
Questions
Why does a comic need a multiple of four pages?
Printed books are folded sheets and each sheet carries four pages. A count that is not a multiple of four leaves blank pages the printer has to add.
How many pages can be saddle stitched?
Usually up to 48 on normal paper, sometimes 64 on thin stock. Thicker books need perfect binding.