Apremilast, etanercept, ustekinumab tied to reduced infection risk in psoriasis
The risk of serious infection* among patients receiving systemic therapy for psoriasis differs by treatment, with apremilast, etanercept, and ustekinumab associated with a reduced risk of serious infection than methotrexate, according to an observational study.
“In addition to being potentially more effective than methotrexate, some of the newer targeted treatments for psoriasis may also be safer for patients in terms of risk of infection,” said study lead author Dr Erica Dommasch from the Beth Israel Deaconess Medical Center, Boston, Massachusetts, US.
Using claims data from two US insurance databases**, the researchers identified 107,707 adults who recently initiated systemic treatment for psoriasis (ie, acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab). Patients receiving acitretin, apremilast, infliximab, and methotrexate had higher baseline comorbidity scores than adalimumab, etanercept, and ustekinumab recipients.
Compared with patients on methotrexate, the risk of serious infection leading to hospitalization was lower among patients on apremilast (adjusted hazard ratio [adjHR], 0.50, 95 percent confidence interval [CI], 0.26–0.94; p=0.03), ustekinumab (adjHR, 0.65, 95 percent CI, 0.47–0.89; p=0.01), or etanercept (adjHR, 0.75, 95 percent CI, 0.61–0.93; p=0.01). [JAMA Dermatol 2019;10.1001/jamadermatol.2019.1121]
There was no apparent difference in the risk of serious infection between methotrexate users and adalimumab (adjHR, 1.08, 95 percent CI, 0.88–1.33; p=0.47), infliximab (adjHR, 1.47, 95 percent CI, 0.75–2.87; p=0.26), or acitretin (adjHR, 1.09, 95 percent CI, 0.83–1.44; p=0.55) users.
The most frequent serious infections in all treatment groups were pneumonia, cellulitis, and bacteraemia or sepsis. Patients on acitretin had an elevated risk of developing cellulitis or soft-tissue infection compared with methotrexate recipients (adjHR, 1.76, 95 percent CI, 1.11–2.80; p=0.02). Conversely, etanercept recipients had a reduced risk of developing bacteraemia or sepsis (adjHR, 0.51, 95 percent CI, 0.32–0.82; p=0.01) and ustekinumab recipients had a reduced risk of developing pneumonia (adjHR, 0.53, 95 percent CI, 0.32–0.88; p=0.01) than methotrexate recipients.
The elevated risk of cellulitis, but not overall serious infections, with acitretin may be due to an increased risk of Staphylococcus aureus infections with retinoids, a class to which acitretin belongs, said the researchers.
In a separate analysis with adalimumab as a reference, apremilast and etanercept were associated with a reduced risk of serious infections (adjHR, 0.31; p=0.002 and adjHR, 0.76; p=0.01, respectively), while infliximab was associated with an elevated risk (adjHR, 1.92; p=0.04).
Previous research has pointed to the superior efficacy of infliximab in treating moderate-to-severe psoriasis, in contrast to the less efficacious etanercept. [Br J Dermatol 2008;159:513-526] This suggests higher and lower immunosuppressive ability, respectively, said the researchers.
“We suspect that the decreased risk of serious infection among users of etanercept compared with methotrexate, but not the other two anti-tumour necrosis factor agents (adalimumab and infliximab), may be owing to a dosing effect,” they said. They also highlighted that infliximab “carries [a] higher risk of inducing neutralizing antibodies”.
Another less efficacious agent, apremilast, [Prescrire Int 2016;25:149-151] was also associated with a reduced infection risk, which could be due to its mechanism of action that “does not directly target inflammatory cytokines”, while ustekinumab may have been “less broadly immunosuppressive”, they said.
They acknowledged that the severity of psoriasis, which was not documented in this study, could have affected the risk of serious infections.
According to the researchers, low adherence is a problem among patients receiving systemic treatment for psoriasis, largely due to infection. “[The results from this study] should be considered when prescribing therapies for individual patients, as well as future treatment algorithms,” they said.