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What If The Medication Appears to Be Less Effective Over Time ?

That sometimes does occur when these type of medications are used to interrupt processes involving the immune system.

Although many dog owners write to me that the drug is just as effective after a year as it was initially, some have noticed that it is no longer as effective at the same dose as it once was.  Increasing the dose might help, but that might also increase the risk.

Your pet’s immune system – the system at which Apoquel is directed – is a dynamic ever-changing policing system. It has to be, because its prime function is to block invaders that are constantly shifting their strategies. Your pet’s immune system has many player (cell types). Research scientists have found that some of these player can adapt and continue their activities (persistence mechanisms) even when the pet's initial alarm messenger chemicals have been removed by medications.

Something like that is thought to occur with another JAK-inhibitor medication that targets JAK1 & 2 in the treatment of immune system tumors (myeloproliferative diseases) in humans.  That drug, ruxolitinib (Jakafi®) works well at first, but after some months it is often less effective.

With that medication, taking a break (a "breather") rather than upping the dose seems to restore its effectiveness.  Perhaps that might be good advice for pet owners as well.