“Superresponders” at biologic treatment for psoriasis: A comparative study among <scp>IL17</scp> and <scp>IL23</scp> inhibitors

Abstract

Dear Editor. Biologics over the past 20 years have changed the treatment of psoriasis.1, 2 The need to switch biologics due to failure after prolonged use, or adverse events (AEs), has increased the proportion of patients with histories of biological failure or biologic-experienced.1, 3 Nevertheless, patients showing a rapid response are becoming increasingly common.4 The latter can be called super responders (SR).4 There is no consensus on the definition of SR concerning psoriasis.4 Reich et al.5 in the sub-analysis of Voyage 1 and 2 studies defined SRs as patients that achieved a PASI (psoriasis area severity index) 100 response at either week 20 or 28. Feldman et al.6 refer SR to patients that reach PASI100 at Weeks 12 and 24, and Eyerich et al.5 to patients that reach PASI100 by week 20 and maintain it at 28 weeks. Loft et al.7 defined SRs were patients treated with their first biologic for a minimum of 5 years PASI < 3 maintained between 6 months and 5 years of treatment. On the base of our real-life experience, we have defined SR as a patient who presents a fast and exceptional improvement with the first biological treatment: bio-naïve patients that reached PASI100 by the 16th week and maintained at 28th. We conducted a retrospective study on psoriatic patients treated with Il17 and Il23 inhibitors at the dermatology clinic of the Turin University Hospital to better characterize this population. Out of 1053 patients with the initial response to treatment with anti-IL17 and anti-Il23, 283 patients fell within our definition of SRs. Some demographic and disease patterns that might be more frequently associated with SRs than non-SRs were then analysed (table 1). Superresponder patients were found to be younger (mean age 52.2 SD 15.9 vs. 55.6 SD 15.4 p < 0.001) with lower BMI (25.9 SD 4.6 vs. 27.5 SD 5.8 p < 0.001) and with earlier onset of psoriasis (age 32.6 SD 17.6 vs. 35.9 SD 17.5 p < 0.001), than non-SR, no differences in disease duration were observed. Concerning comorbidities, lower rates of obesity and diabetes mellitus were observed (16.2% vs. 25.7% p < 0.001, and 7.4% vs. 13.8% p = 0.008). No significant differences were found for joint involvement and difficult sites (scalp, nails, folds, palms and soles). Superresponders have a higher initial PASI than non-SRs (15.3 vs. 14.4 p = 0.037), but not mean Dermatology Life Quality Index (DLQI) at baseline. Concerning biologic therapies SRs are more likely to be treated with anti-IL17 (p < 0.001), with ixekizumab and brodalumab being the drugs with the highest number of SRs (35.5% and 30.5%). Superresponders had a lower frequency of drug discontinuation (11.7% vs. 22% p < 0.001). In the literature, the patterns associated with the various definitions of SR were low body weight and BMI, lower obesity rate, less traditional systemic drugs used before the first biologic, and lower disease severity at baseline.5, 7 Talamonti et al.8 showed a faster response in patients with HLA-C*06:02 positive, generally younger and with lower disease severity at baseline. Feldman et al. showed a correlation between rapid reduction in the DLQI and Visual Analogue Scale for pain and SR status. Our results are in line with what has been reported in the literature, despite the slightly different definition. Superresponders are younger patients, with lower rates of obesity, diabetes mellitus and lower weight, and have an earlier development of disease than non-SRs. The higher initial mean PASI is related to the bio-naive condition. The higher rate of anti-Il17 gives reason for the higher frequency of SRs being treated with these biologics.9 The monocentric and retrospective nature are the main limitations of this study, highlighting the need for dedicated studies, clinical and translational, to arrive at a shared definition of this special population. LM wrote the paper, performed the research, designed the research study and analysed the data. SS, CC, GA, AV, ES and MO performed the research. PQ contributed essential reagent tools. PD contributed essential reagent tools and performed the research. SR designed the research study, analysed the data and contributed essential reagent tools. None. None.

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