Scrolling and clicking are the big attributers to RSI. What you can do is to pick a mouse / controller that has the least possible activation force (every microswitch in there has a certain force you need to apply to activate/click it). The less force it requires, the better for your wrist. This is also the reason I use a tablet, as their activation force is far less than any mechanical switch.
Wrist position also plays a role, so those ‘vertical’ or titled mice are better, but also don’t forget your shoulders (good elbow rest on your chair and adjusted height of your desk help).
The real reason arpg games require you to click so much, and even ban players for using hardware or software (like autohotkey scripts) solutions to the rsi (and some even despise ‘passive’ playstyles like a summoner), is competition - other players complain it’s unfair if you can get away with clicking once every minute, while they do it 40 times a minute. Silly, really, but that’s what a leaderboards mechanics lead to: disqualifiying the less abled.
If scripts are allowed, you can use autohotkey to make your mouse key a ‘toggle’ instead of a momentary switch (default), I’m sure, which gives you the same ‘sticky mouse key’ feature you described.
Alternatively, you can buy/build your own programmable keyboard (I have build a few), using customizable firmware like QMK. Then, you can have keyboard keys act as mouse keys (like a right mouse button or a scroll command), or customise your own macro if you want even.
This way, you can move some/most actions to your other hand, to lighten / distribute the strain on your body.
PS. I also built a keyboard with one of the (discontinued now) Cherry MX toggle switches, which locks / unlocks mechanically on each press (mapped onto a RMB), but they are useless for typing, so unless you’re building a dedicated gaming keypad, I do not recommend them