Overall, targeted immune modulators are highly effective medications for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis that substantially improve the burden of disease and are generally safe for short-term treatment. The evidence is currently insufficient to reliably determine the comparative effectiveness and safety for most comparisons. In addition, for many drugs the balance between benefits and risks cannot be reliably assessed without sound long-term (> 12 months) data on safety.