Risk of Cutaneous T Cell Lymphoma with Psoriasis Biologic Therapies.

BACKGROUND: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.

Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

Mendelian Randomization Studies in Psoriasis and Psoriatic Arthritis: A Systematic Review.

Psoriasis (PSO) and psoriatic arthritis (PSA) are inflammatory diseases with complex genetic and environmental contributions. Although studies have identified environmental and clinical associations with PSO/PSA, causality is difficult to establish. Mendelian randomization (MR) employs the random assortment of genetic alleles at birth to evaluate the causal impact of exposures. We systematically reviewed 27 MR studies in PSO/PSA examining health behaviors, comorbidities, and biomarkers. Exposures, including smoking, obesity, cardiovascular disease, and Crohn's disease, were causal for PSO and PSA, whereas PSO was causally associated with several comorbidities. These findings provide insights that can guide preventive counseling and precision medicine.