Implementing Negative Control Outcomes to Assess Comparability of Treatments for Psoriasis and Psoriatic Arthritis

Abstract

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.

Keywords: apremilast; biologics; methotrexate; negative control outcome; psoriasis; psoriatic arthritis; topicals.

FIGURE 1

Study design (A) and overview of NCOs assessed (B). NCO, negative control outcome; PsA, psoriatic arthritis; PsO, psoriasis.

FIGURE 2

One‐year weighted relative risk of NCOs for patients with PsO initiating apremilast vs. topicals among (A) all treatment initiators and (B) patients with ≥ 1 topical prescription prior to index. Error bars represent 95% CI. The 1‐year cumulative risk was estimated using IPTCW, and the 1‐year cumulative RR was calculated using inverse probability weighting. CI, confidence interval; IPTCW, inverse probability of treatment and censoring weights; NCO, negative control outcome; PsO, psoriasis; RR, relative risk.

FIGURE 3

One‐year weighted relative risk of NCOs for patients with PsO or PsA initiating apremilast vs. methotrexate. Error bars represent 95% CI. The 1‐year cumulative risk was estimated using IPTCW, and the 1‐year cumulative RR was calculated using inverse probability weighting. CI, confidence interval; IPTCW, inverse probability of treatment and censoring weights; NCO, negative control outcome; PsA, psoriatic arthritis; PsO, psoriasis; RR, relative risk.

FIGURE 4

One‐year weighted relative risk of NCOs for patients with PsO or PsA initiating apremilast vs. biologics in (A) apremilast vs. IL‐17i initiators, (B) apremilast vs. IL‐12/23i initiators, and (C) apremilast vs. TNFi initiators. CI, confidence interval; IPTCW, inverse probability of treatment and censoring weights; NCO, negative control outcome; PsA, psoriatic arthritis; PsO, psoriasis; RR, relative risk; TNFi, tumor necrosis factor inhibitor.