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 I'm using a list of "spam-safe" relays but apparently I am missing a lot of replies from people whose clients are sending their replies to my inbox relays.

When browsing other people's notes, though, this technique doesn't work well or needs more thought because people replying to others are not going to send their replies to my own inbox list of relays. 
 Pay Hurdles. 
Have rate thresholds that trigger when X (e.g. 3 posts, 16 reactions) events per minute are done. The hurdle is an ecash token run by the relay, payable by zap. When paid the Relay returns an ecash token of bigger size.
This progressively scales the resistance. If no hurdle payment made with 30 days the content is pruned from the relay into cold storage (this keeps integrity). The pay hurdle will immediately ruin spammers, but allows new users to onboard (post and and like) without difficult setup.