Patient-reported assessment of medical care for chronic inflammatory skin diseases: an enterprise-based survey.

Background: Chronic inflammatory skin diseases (CISDs) are among the most common diseases in the Western world. Current estimates of medical care for CISDs are primarily based on surveys among patients in medical care facilities and on health insurance data. Aim: Survey-based examination to what extent CISD patients in health-aware environment consider their skin disease to be controlled. Methods: The survey of CISD patients was carried out in 2022 among the employees of a pharmaceutical company located in Germany and Switzerland. Software-based, anonymous, self-reported questionnaires were used. Results: The number of employees, who answered the questionnaire, was 905. Of these, 222 participants (24.5%) reported having at least one CISD. 28.7% of participants with CISD described their disease as being hardly or not controlled. Regarding the nature of disease, more than one third of participants suffering from hidradenitis suppurativa (HS) or psoriasis fell into the hardly/not controlled category. In contrast, the largest proportion of participants with chronic spontaneous urticaria (43%) or atopic dermatitis (42%) considered their CISD to be completely or well controlled. Only 35.5% of CISD sufferers stated that they were currently under medical care for their skin condition. Being under medical care, however, had no influence on the extent CISD sufferers considered their skin disease to be controlled. The number of active CISD episodes but not the total number of symptomatic days per year was negatively associated with poor disease control (p = 0.042 and p = 0.856, respectively). Poor disease control had a negative effect on the personal and professional lives of those affected, as deduced from its positive association with the extent of daily activity impairment and presenteeism (p = 0.005 and p = 0.005, respectively). Moreover, 41.4 and 20.7% of participants with hardly/not controlled disease stated that their CISD had a moderate and severe or very severe impact on their overall lives (p < 0.001), respectively. A severe or very severe impact of their CISD on their overall life was most commonly reported by participants with HS. Conclusion: Medical care for CISDs, even in an environment with high socio-economic standard and high health-awareness, still appears to be limited and has a negative impact on individuals and society.

Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2.

Purpose: Antibody-drug conjugates and small-molecule-drug conjugates have been proposed as alternatives to conventional anticancer cytotoxic agents, with the potential to deliver bioactive payloads to the site of disease, helping spare normal tissues.Experimental Design: Here, we describe a novel small-molecule-drug conjugate, based on a high-affinity ligand specific to carbonic anhydrase IX. The product featured a peptidic linker, suitable for cleavage in the tumor extracellular environment, and monomethyl auristatin E as cytotoxic payload.Results: A potent anticancer activity was observed in nude mice bearing SKRC-52 renal cell carcinoma xenografts, but no durable complete responses could be observed in this model. However, when the product was administered together with L19-IL2 (a clinical-stage fusion protein capable of delivering IL2 to the tumor neovasculature), all treated mice in the combination group could be rendered tumor free, in a process that favored the influx of natural killer cells into the tumor mass. The combination of L19-IL2 and the new small-molecule-drug conjugate also eradicated cancer in 100% of immunocompetent mice, bearing subcutaneously grafted CT26 colorectal cancer cells, which stably expressed carbonic anhydrase IX.Conclusions: These findings may be of clinical significance, because carbonic anhydrase IX is overexpressed in the majority of clear cell renal cell carcinomas and in approximately 30% of colorectal cancers. The targeted delivery of IL2 helps potentiate the action of targeted cytotoxics, leading to cancer eradication in models that cannot be cured by conventional chemotherapy. Clin Cancer Res; 24(15); 3656-67. ©2018 AACR.

Chemically Defined Antibody- and Small Molecule-Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis.

We present the first direct comparative evaluation of an antibody-drug conjugate and of a small molecule-drug conjugate for cancer therapy, using chemically defined products which bind with high-affinity to carbonic anhydrase IX, a marker of tumor hypoxia and of renal cell carcinoma.