Patient experiences with biologics and apremilast in pityriasis rubra pilaris: A patient survey

Dear Editor Pityriasis rubra pilaris (PRP) is a papulosquamous disorder that sometimes fails to respond favorably to oral retinoids or methotrexate (Klein, Landthaler, & Karrer, 2010). Tumor necrosis factor (TNF)-α inhibitors, ustekinumab, interleukin (IL)-17 inhibitors, and apremilast have been reported to be helpful for PRP (Krase, Cavanaugh, & Curiel-Lewandrowski, 2016; Napolitano, Abeni, & Didona, 2018). Limited data sets describe PRP treatment with biologics or apremilast due to the disease's rarity (Eastham, Femia, Qureshi, & Vleugels, 2014; Kromer, Sabat, Celis, & Mössner, 2019; Napolitano et al., 2018). Thus, publication bias for positive outcomes is possible, and the efficacy of these agents is unclear. To gather data on PRP responses to these drugs in real-world experience, we created an anonymous Qualtrics survey distributed via an International PRP Support Group, the PRP Alliance. The survey focused on demographic information, clinical history/features, and treatment regimens and responses. Patients needed to report an unequivocal diagnosis of PRP from their dermatologist (their dermatologist confirmed that their disease is not psoriasis or another PRP mimic) and have received at least one biologic or apremilast for inclusion in the study. In total, 625 responses were recorded and of these, 583 patients had a clear diagnosis of PRP. Of these, 168 patients had received at least one biologic or apremilast for PRP. Baseline characteristics are found in Table 1. Patients reported either “complete clearance,” “substantial improvement,” “slight improvement,” or “no improvement” with response to a regimen. Biologic use for PRP is frequent with 28% of patients reporting attempting a biologic. Patients reported finding ustekinumab and TNF inhibitors to be the most helpful biologics, with less improvement reported from IL-17 inhibitors (Table 2). However, while many individual biologics failed to cause improvement, those who received additional alternative biologics reported improvements. Of the 166 biologic users, 142 patients reported at least a slight improvement in symptoms from a biologic regimen. Of patients who failed their first biologic regimen and subsequently received a second biologic, 16 of 29 reported improvement. Of 45 patients who attempted two different classes of biologics, 39 experienced at least some improvement in their symptoms. For the most treatment-refractory patients who reported attempting three different classes of biologics (TNF-α, IL-12/23, and IL-17 blockade), only one of eight patients completely failed to show any improvement. Patients reported receiving relatively less benefit from apremilast. In comparison to the published literature, which reports rates of marked improvement or complete clearance in 50–78% of patients on biologics, similar proportions of patients reported achieving these outcomes in our study on ustekinumab or TNF inhibitors (Kromer et al., 2019; Napolitano et al., 2018). In pediatric patients, TNF inhibitors were the most frequently used, but they resulted in less subjective improvement than ustekinumab (Table 3). Patient-reported adverse effects to biologics were consistent with their known adverse effect profile, and included fatigue, infusion reactions, hepatotoxicity, headache, nausea and tuberculosis; however, the exact frequencies of these are confounded by concomitant therapies such as retinoids/methotrexate in this study. Limitations of this study included that drug responses were reported by patients and thus subjective. Other confounders included the potential for attributing spontaneous improvement/resolution over