Background/Purpose: Ustekinumab (UST), an anti IL12/IL23 monoclonal antibody, is a relatively new biologic used for the treatment of psoriasis (PSO) and psoriatic arthritis (PSA). Its safety profile in real world practice has not been well characterized to date. We assessed the incidence rate (IR) of acute myocardial infarction (AMI) in ustekinumab users and compared it to the corresponding rate for patients treated with tumor necrosis factor inhibitors (TNFi).

Methods: We conducted a retrospective, new user design cohort study of PSO and PSA patients initiating UST or TNFi using 2010-2014 Market scan and 2006-2014 Medicare data. To be included in the cohort, patients have to have at least 12 consecutive months of medical and pharmacy coverage before first prescription date of UST or TNFi (index date). Patients were excluded if they have any of the following: inflammatory disease other than PSO or PSA, prior MI, prior PCI/CABG, malignancy (except non-melanoma skin cancer), HIV, or organ transplant. A sensitivity analysis had more stringent exclusions for patients with past evidence for acute coronary syndrome, angina, or coronary atherosclerosis. Follow up started at index date and ended at earliest of: discontinuation of the index drug (90 days after days of supply), switch to another biologic, the outcome, loss of insurance coverage, death, or end of study (12/31/2014). Patients contributed to only one episode of one specific drug but could contribute to multiple drugs, and standard errors were adjusted to account for this clustering. AMI was identified using diagnosis codes from hospital discharge (Primary or non-primary).  Incidence rates (IR) were calculated by dividing number of outcomes by person year exposed. Crude and multi-variable adjusted hazard ratios (HR) were calculated with Cox proportional hazard regression, controlling for potential confounders.

Results: The final cohort included 46,338 initiations of UST or TNFi (17,750 from Medicare, 28,588 from Market scan) representing 39,469 unique patients. Demographic characteristics of the cohort were: age 50.2 (14.9) years, women 54.8%. A total of 181 MIs occurred in 41,302 person years, resulting in an overall IR of 4.38 (3.79, 5.07) per 1000 person years.  The crude IRs were 4.62 (2.87, 7.43) for ustekinumab and 4.36(3.74, 5.08) for TNFi (Table). Compared to TNFi, and after multivariable adjustment for potential confounders, the rate of MI for UST-treated patients was not significantly different (HR=1.26, 95% CI 0.76, 2.10) compared to TNFi users (referent). Sensitivity analysis yielded similar results.

Conclusion: In patients with psoriasis and psoriatic arthritis, the rate of myocardial infarction associated with ustekinmab was comparable to the corresponding rate in TNFi users.

<>IR: Incidence rate, per 1000 person years. UST: ustekinumab; CI: Confidence interval; HR: Hazard ratio <>*Adjusted for age, gender, diabetes hyperlipidemia, hypertension, obesity, chronic kidney disease, chronic obstructive pulmonary disease, pneumonia, heart failure, sepsis, peptic ulcer disease, fracture,  skin ulcer, glucocorticoid use, prior biologic use, smoking status, prostate specific antigen screen, mammography, pap smear, hospitalization in baseline, number physician visit. <>** Excluded MI, history of MI, malignancy (except non-melanoma skin cancer) or HIV or organ transplant or procedure for percutaneous coronary intervention or coronary artery bypass graft. <>*** Further excluded coronary syndrome, angina, and coronary atherosclerosis.