Feel free to exile or assassinate them.
Is exile even a major problem for a royal duke? I mean don't they still get gold, not bonds, every tax so long as they're in the realm? If that is the case, shouldn't an exiled duke be able to outlast a ruler almost always?
As for assassination, if a Duke is incapacitated can the ruler appoint another? I've seen this brought up a few times, but I don't know if it is actually a solution.