Biologic Agents May Reduce Risk of Mental Health Disorders in Some Patients with Psoriasis

Raymond Milan, MSc

Patients with psoriasis who discontinued conventional systemic agent treatment had a reduced risk of depression, anxiety and adjustment disorder after receiving tumor necrosis factor (TNF) inhibitors or ustekinumab, a recent study found.

The retrospective cohort study included data from Quebec health administration databases on adults diagnosed with psoriasis between 1997 and 2015.

It included 1333 patients with psoriasis, including 183 treated with TNF inhibitors or ustekinumab, 625 current users of conventional systemic agents (CSA) and 525 previous CSA users.

Patients with moderate-to severe psoriasis who received TNF inhibitors or ustekinumab after failing CSA treatment had a 52% reduced risk of depression, anxiety and adjustment disorder than those who had discontinued CSA treatment (hazard ratio [HR], 0.48; 95% CI, 0.28 - 0.93), the study found. Among those who continued CSA treatment, a nonsignificant reduction in risk of mental health disorders was observed (HR, 0.48; 95% CI, 0.28 - 0.93).

Patients with psoriasis are at higher risk of depression, anxiety and adjustment disorder than the general population. Biologic agents have been more effective than conventional systemic agents, such as methotrexate, in improving psoriasis, trials have shown.

"Randomized controlled trials have found a decreased risk of mental health disorders with TNF inhibitors or ustekinumab compared to CSA and placebo in patients with moderate to severe psoriasis," first author Raymond Milan, MSc, of McGill University told HCPLive®. "However, the risk of mental health disorders was not previously compared among patients who received TNF inhibitors or ustekinumab after having failed CSA versus those who continued on CSA and those who discontinue CSA treatment for any reason."

“One would assume that patients receiving a TNF inhibitor or ustekinumab after failing CSA should be at higher risk of mental health outcomes than those who continue using CSA (presumably did not fail CSA) or using CSA (presumably no longer needed treatment),” he said. “However, my findings suggested otherwise, which is reassuring for those who use TNF inhibitors or ustekinumab, but disturbing for those who discontinue CSA treatment, as some seem to have discontinued because of CSA failure.”

The study was consistent with previous randomized controlled trials and observational studies. Further research is needed to determine the reason for discontinuation of CSA, including whether they may contribute to mental health improvement or deterioration.

“Those who discontinue because of CSA failure or mental health issues, should be offered TNF inhibitors or ustekinumab treatment if not contraindicated in them for health reasons,” Milan said. “In addition, on the health care system level, improving access to biologic agents for patients with moderate-to-severe psoriasis at high risk of CSA failure may save them the burden of going through a failed treatment experience and help improve their psoriasis outcomes, mental health outcomes and quality of life faster, especially since biologic agents are known for being more effective than CSA.”

Limitations of the study include a lack of data on psoriasis severity, health-related quality of life or physician advocacy for access to biologics. The study also didn’t assess biologic agents individually or consider switches in treatment.

“Future studies should include patients receiving newer generation of biologic agents such as interleukin 23 and 17 inhibitors,” Milan said. “Future studies should also be multi-province to increase the sample size, which will allow the study of the risk of mental health across different systemic agents.

Milan addtionally proposed a mediation analysis in order to determine any direct association between biologic agents and mental health outcomes—or if the link is indirectly related to quality-of-life and skin clearance outcomes.

"This type of study will determine the additional risk of having depression, anxiety and adjustment disorder in patients who have versus those who have not improved quality of life and/or skin clearance and will help understand if these clinical measures are full, partial or are not mediators in the association between biologic agents and mental health outcomes," he said.

The study, "Depression, anxiety and adjustment disorder among patients with psoriasis receiving systemic agents: A retrospective cohort study in Quebec, Canada," was published online in JEADV Clinical Practice.