I had to go off Plaquenil/hydroxychloroquine about a year ago. The effects were not immediate, but I did notice some trends after a couple of weeks. In general, I felt like there was less of a buffer from symptoms and flares. For example, while on Plaquenil a single bad night of sleep wouldn't trigger a flare, but after going off I have to be more careful to get a good night's sleep or I'll feel it the next day. Joint pain was also a bit more noticeable.
Since then, I have added some other medications and supplements that have helped make up for the loss of Plaquenil.