PURPOSE: Treatment selection is typically associated with prognosis, leading to potential confounding in comparative studies. We used negative control outcomes (NCOs) to identify potential residual confounding when comparing apremilast initiators to other psoriasis (PsO) or psoriatic arthritis (PsA) treatment initiators. METHODS: Adults with PsO/PsA who initiated treatment from September 23/March 21, 2016, respectively, with apremilast, topicals, methotrexate, interleukin (IL)-17 inhibitor (i), IL-12/23i, or tumor necrosis factor inhibitor (TNFi) were identified in the OPTUM Clinformatics DataMart database. Follow-up ended at treatment switch/discontinuation, NCO, end of enrollment, or September 30, 2022. NCOs addressed confounding for healthy users (wellness visit, herpes zoster vaccine, colon cancer screening, pelvic screening), functional status (accidents), and channeling. The 1-year relative risk (RR) for each NCO was estimated for all treatment comparisons using an inverse probability of treatment and censoring weighted estimator. RESULTS: In PsO, potential healthy user bias was detected in apremilast vs. IL-17i initiators, with a higher likelihood of herpes zoster vaccine and colon cancer screening (RR [95% CI]: 2.01 [1.41, 2.88] and 1.42 [1.13, 1.77], respectively). Wellness visits and pelvic exams were less likely among apremilast vs. topical initiators (0.84 [0.72, 0.98] and 0.83 [0.70, 0.98], respectively). The wellness visit RR was attenuated in individuals with ≥ 1 pre-index topical prescription (0.90 [0.78, 1.04]). In PsA, minimal residual confounding was observed between apremilast and other treatments. CONCLUSIONS: Eligibility criteria (prior topicals) and weighting reduced residual confounding when comparing apremilast vs. other treatments for PsO and PsA. Integration of NCOs into comparative effectiveness/safety studies of PsO/PsA treatments may help identify unmeasured confounding.