Methotrexate
"I took Methotrexate for 17 years.  Started with tablets but progressed to injections for less chance of side effects (and cheaper!).  Always felt tired and nauseous for a day after, which got worse and lasted longer over the years, so that instead of just folic acid, my rheum had me take leucovorin the day after (a stronger folic acid).  But 6 months ago I developed fatigue, malaise and chronic low grade fever despite normal blood tests; my rheum said he had seen that before in other patients taking Methotrexate and considered it a toxic reaction!  There is no literature on this reaction, but I got better once I stopped, so just be aware."