Goals and benefits in topical treatment for psoriasis: development and pilot validation of a patient-reported outcomes tool, the Patient Benefit Index for Topical Treatment (PBI-TOP).

BACKGROUND: Topical agents are an essential component of psoriasis therapy. OBJECTIVES: To develop a new version of the patient-reported Patient Benefit Index assessing the importance and achievement of treatment goals in topical psoriasis therapy in adult patients (PBI-TOP). METHODS: Through semi-structured interviews, focus groups and free-text questionnaires, patients reported their needs in topical treatment. Based on qualitative content analysis, items were developed by a consensus group and were refined in cognitive debriefing interviews. A pilot validation assessed the PBI-TOP and convergent criteria [Dermatology Life Quality Index (DLQI); Psoriasis Area and Severity Index (PASI); affected Body Surface Area (BSA)]. RESULTS: Thirty patients (26-72 years, mean 47; 60% male) reported various treatment goals relating to the themes 'effectiveness' and 'characteristics of the preparation'. Twenty patients took part in cognitive debriefings (22-84 years, mean 50.6, 50% male). There were 154 patients who participated in the pilot validation (18-85 years, mean 46.9, 63.6% male). An importance-weighted total score on overall effectiveness and three subscales based on exploratory factor analysis were defined: effectiveness on symptoms, effectiveness on quality of life (QoL), and characteristics of the preparation. All scores showed excellent internal consistency (α > 0.9). The global effectiveness score correlated significantly with DLQI (r = -0.41), PASI (r = -0.32) and BSA (r = -0.22). The effectiveness subscales (symptoms; QoL) correlated significantly with DLQI (r = -0.41; -0.32) and PASI (r = -0.27; -0.33). The score on characteristics of the preparation correlated significantly with the DLQI (r = -0.34). CONCLUSIONS: The PBI-TOP showed good feasibility and favourable psychometric characteristics in this pilot validation.

IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases.

Innate immunity not only shapes the way epithelial barriers interpret environmental cues but also drives adaptive responses. Therefore, modulators of innate immune responses are expected to have high therapeutic potential across immune-mediated inflammatory diseases. IRAK4 is a kinase that integrates signaling downstream of receptors acting at the interface between innate and adaptive immune responses, such as Toll-like receptors (TLRs), interleukin-1R (IL-1R), and IL-18R. Because effects of IRAK4 inhibition are stimulus, cell type, and species dependent, the evaluation of the therapeutic potential of IRAK4 inhibitors requires a highly translational approach. Here, we profiled a selective IRAK4 inhibitor, GLPG2534, in an extensive panel of models of inflammatory skin diseases, translationally expanding evidence from in vitro to in vivo and from mouse to human. In vitro, IRAK4 inhibition resulted in substantial inhibition of TLR and IL-1 responses in dendritic cells, keratinocytes, granulocytes, and T cells but only weakly affected dermal fibroblast responses. Furthermore, disease activity in murine models of skin inflammation (IL-23-, IL-33-, imiquimod-, and MC903-induced) was markedly dampened by IRAK4 inhibition. Last, inhibiting IRAK4 reversed pathogenic molecular signatures in human lesional psoriasis and atopic dermatitis biopsies. Over the variety of models used, IRAK4 inhibition consistently affected central mediators of psoriasis (IL-17A) and atopic dermatitis (IL-4 and IL-13). Overall, our data highlight IRAK4 as a central player in skin inflammatory processes and demonstrate the potential of IRAK4 inhibition as a therapeutic strategy in chronic inflammatory skin diseases.

Switching from Adalimumab Originator to Biosimilar in Patients with Hidradenitis Suppurativa Results in Losses of Response-Data from the German HS Registry HSBest.

Since 2021, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). Effectiveness and safety data remain scarce. We investigated the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analyzed clinical data on patients enrolled in the German HSBest registry. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. In total, 94 patients were switched from ADAO to ABP 501. Overall, 33.3% (n = 31/94) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switching. Of these, 61.3% (n = 19/31) experienced LoR but no AEs, 22.6% (n = 7/31) LoR combined with AEs and 16.1% (n = 5/31) AEs only. Our study showed that switching HS patients from ADAO to ABP 501 does significantly affect treatment effectiveness. Switching patients who are on remission maintenance therapy should be viewed critically.