Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population.

BACKGROUND: Moderate to severe psoriasis often requires treatment with systemic agents, many of which have immunosuppressive properties and could increase cancer risk, including nonmelanoma skin cancer (NMSC). OBJECTIVE: We sought to estimate the overall malignancy rate (excluding NMSC) and NMSC rate among 5889 patients with systemically treated psoriasis. METHODS: We identified a cohort of adult Kaiser Permanente Northern California health plan members with psoriasis diagnosed from 1998 to 2011 and treated with at least 1 systemic antipsoriatic agent and categorized them into ever-biologic or nonbiologic users. Malignancy rates were calculated per 1000 person-years of follow-up with 95% confidence intervals (CI). Crude and confounder-adjusted hazard ratios (aHRs) were calculated using Cox regression. RESULTS: Most biologic-exposed members were treated with TNF-alfa inhibitors (n = 2214, 97%). Overall incident cancer rates were comparable between ever-biologic as compared to nonbiologic users (aHR 0.86, 95% CI 0.66-1.13). NMSC rates were 42% higher among individuals ever exposed to a biologic (aHR 1.42, 95% CI 1.12-1.80), largely driven by increased cutaneous squamous cell carcinoma risk (aHR 1.81, 95% CI 1.23-2.67). LIMITATIONS: No information was available on disease severity. CONCLUSION: We found increased incidence of cutaneous squamous cell carcinoma among patients with systemically treated psoriasis who were ever exposed to biologics, the majority of which were TNF-alfa inhibitors. Increased skin cancer surveillance in this population may be warranted.

Serious infections among a large cohort of subjects with systemically treated psoriasis.

BACKGROUND: Biologic therapy is effective for treatment of moderate-to-severe psoriasis but may be associated with an increased risk for serious infection. OBJECTIVE: To estimate the serious infection rate among patients with psoriasis treated with biologic as compared with nonbiologic systemic agents within a community-based health care delivery setting. METHODS: We identified 5889 adult Kaiser Permanente Northern California health plan members with psoriasis who had ever been treated with systemic therapies and calculated the incidence rates and 95% confidence intervals (CIs) for serious infections over 29,717 person-years of follow-up. Adjusted hazard ratios (aHRs) were calculated using Cox regression. RESULTS: Adjusting for age, sex, race or ethnicity, and comorbidities revealed a significantly increased risk for overall serious infection among patients treated with biologics as compared with those treated with nonbiologics (aHR, 1.31; 95% CI, 1.02-1.68). More specifically, there was a significantly elevated risk for skin and soft tissue infection (aHR, 1.75; 95% CI, 1.19-2.56) and meningitis (aHR, 9.22; 95% CI, 1.77-48.10) during periods of active biologic use. LIMITATIONS: Risk associated with individual drugs was not examined. CONCLUSION: We found an increased rate of skin and soft tissue infections among patients with psoriasis treated with biologic agents. There also was a signal suggesting increased risk for meningitis. Clinicians should be aware of these potential adverse events when prescribing biologic agents.

Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up: the ziprasidone observational study of cardiac outcomes (ZODIAC).

PURPOSE: The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real-world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD-10 coding rules for sudden death. METHODS: A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD-10 rules. Relative risks (RR) and corresponding 95%CI were calculated for persons randomized to ziprasidone versus olanzapine, comparing 1-year incidence of sudden death, using multiple definitions. RESULTS: Data on symptom onset to death and diagnosis of specific cardiac arrhythmias required by the ICD-10 rules were often lacking. Sensitivity analyses were conducted to explore the impact of cases suggestive of cardiac origin but missing data required by ICD-10 sudden death codes. Overall, the readjudicated data matched the study's initial findings, with no significant difference in 1-year mortality between ziprasidone and olanzapine for sudden death not otherwise specified and sudden cardiac death (R96.0 or R96.1 or I46.1; RR = 1.11, 95%CI 0.45- 2.77). CONCLUSIONS: After outcome readjudication, ZODIAC found no difference in the risk of sudden death among those randomized to ziprasidone versus olanzapine. However, unlike hospital-based studies, fatal events in general population studies often occur outside hospital and often lack the clinical detail needed for the exact determination of symptom onset and event. Epidemiological evaluations of sudden death need to consider the limitations of the available data.