Topical corticosteroids, such as hydrocortisone, have proven effective in managing AD. If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors like tacrolimus or pimecrolimus may be tried, although their use is controversial as some studies indicate that they increase the risk of developing skin cancer or lymphoma. A 2007 meta-analysis showed that topical pimecrolimus is not as effective than corticosteroids and tacrolimus. However a 2015 meta-analysis indicated that topical tacrolimus and picrolemus are more effective than low dose topical corticosteroids, and found no evidence for increased risk of malignancy or skin atrophy.  Other alternatives include systemic immunosuppressants such as ciclosporin, methotrexate, interferon gamma-1b, mycophenolate mofetil and azathioprine.  Antidepressants and naltrexone may be used to control pruritus (itchiness).  In 2016, crisaborole was approved as a topical treatment for mild-to-moderate eczema.  In 2017, the biologic agent dupilumab was approved to treat moderate-to-severe eczema.