PSOLAR, the Psoriasis Longitudinal Assessment and Registry, is a multicenter, longitudinal, intercontinental, disease-based registry used to identify adverse events from commonly used psoriasis drugs.1 An evaluation of the risk of serious infection from systemic psoriasis treatments was recently published using data from PSOLAR. Ninety-three institutional review boards or ethics committees reported into the registry from regions that included North America, Europe, the Middle East and Latin America. Data were collected from June 20, 2007, through Aug. 23, 2013.
Serious adverse events were submitted and evaluated in real time. Collection of data occurred at entry into the registry and for approximately six months. Results from PSOLAR suggest a higher risk of serious adverse events. Patients receiving the biologics adalimumab, etanercept, infliximab and ustekinumab were evaluated in separate cohorts and statistically analyzed. Other agents that were either investigational, no longer available, not currently indicated for psoriasis or not used enough to perform statistical analysis were not evaluated. These agents included abatacept, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, golimumab and secukinumab. Some of the nonbiologic therapies included methotrexate (MTX), systemic retinoids, and psoralen plus UVA and UVB. Serious infections were defined as having at least one of the following criteria: death, a life-threatening condition, persistent or significant disability or incapacitation, causing or prolonging hospitalization, or causing or prolonging another medically important condition.
Overall, 11,466 psoriatic patients were analyzed. 9,145 patients received a biologic agent, 490 received MTX and possibly other non-biologics, and 1,610 patients did not receive MTX or biologics. Cumulative incidence rates of serious infections were 1.45 per 100 patient-years (n = 323) across treatment cohorts. Individual drug/class rates were 0.83 per 100 patient-years for ustekinumab, 1.47 per 100 patient-years for etanercept, 1.97 per 100 patient-years for adalimumab and 2.49 per 100 patient-years for infliximab. Rates of serious infections in the non-biologics cohorts were 1.05 per 100 patient-years for non-MTX/non-biologics and 1.28 per 100 patient-years for the MTX/non-biologics cohorts. Infections with adalimumab and infliximab were comparable to infections with non-MTX/non-biologic therapies. No increased risk was observed with etanercept or ustekinumab treatment.
Pneumonia and cellulitis were the most common types of serious infections. Isolated incidents of necrotizing fasciitis (n = 4), tuberculosis (n = 2), histoplasmosis (n = 2), hepatitis C (n = 1) and salmonella bacteremia (n = 1) were reported. Overall, six patients developed serious infections that resulted in death. Increased risk of serious infection was associated with the following demographics: increased age, diabetes mellitus, smoking, a significant history of infection, infliximab exposure and adalimumab exposure.
Despite Setbacks, Brodalumab Trials Continue
Brodalumab, an interleukin (IL) 17 inhibitor, is currently in early clinical trials (Phase 1b and Phase 2) for a number of different autoimmune diseases.2 Amgen recently terminated its co-development and commercialization agreement with AstraZeneca for the brodalumab investigational program in trials for moderate to severe plaque psoriasis, psoriatic arthritis and axial spondyloarthritis. Amgen’s decision to sever ties with AstraZeneca for this compound was due to the potential for restrictive labeling (if approved) because of suicidal ideation and suicidal behavior already identified in brodalumab trials. AstraZeneca continues to investigate this agent.3