Summary Background HSP90 is a downstream regulator of tumour necrosis factor (TNF)‐α and interleukin (IL)‐17A signalling and may therefore serve as a novel target in the treatment of psoriasis. Objectives This phase Ib proof‐of‐concept study was undertaken to evaluate the safety and efficacy of a novel HSP90 inhibitor (RGRN‐305) in the treatment of plaque psoriasis. Methods We conducted an open‐label, single‐arm, dose‐selection, single‐centre proof‐of‐concept study. Patients with plaque psoriasis were treated with 250 mg or 500 mg RGRN‐305 daily for 12 weeks. Efficacy was evaluated clinically using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), Physician’s Global Assessment (PGA) scores and the Dermatology Life Quality Index (DLQI). Skin biopsies collected at baseline and at 4, 8 and 12 weeks after initiation of treatment were used for immunohistochemical staining and for gene expression analysis. Safety was monitored via laboratory tests, vital signs, electrocardiogram and physical examinations. Results Six of the 11 patients who completed the study responded to RGRN‐305 with a PASI improvement between 71% and 94%, whereas five patients were considered nonresponders with a PASI response < 50%. No severe adverse events were reported. Four of seven patients treated with 500 mg RGRN‐305 daily experienced a mild‐to‐moderate exanthematous drug‐induced eruption owing to the study treatment. Two patients chose to discontinue the study because of this exanthematous eruption. RGRN‐305 treatment resulted in pronounced inhibition of the IL‐23, TNF‐α and IL‐17A signalling pathways and normalization of both histological changes and psoriatic lesion gene expression profiles in patients who responded to treatment. Conclusions Treatment with RGRN‐305 showed acceptable safety, especially in the low‐dose group, and was associated with clinically meaningful improvement in a subset of patients with plaque psoriasis, indicating that HSP90 may serve as a novel future target in psoriasis treatment.

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Background: Dead Sea climatotherapy (DSC) is a treatment option for psoriasis in Denmark. However, the response to DSC has not been particularly well studied. Aim: We sought to determine effectiveness and response duration of DSC on psoriasis-related outcome parameters. Methods: Eighteen patients participated in a 4-week treatment program in Ein Gedi in Israel. Treatment, consisting of sun exposure and bathing, was individualized. Results: DSC was associated with a mean 13.0-point reduction (88%) in Psoriasis Area and Severity Index and a mean reduction of 2.3 (76.7%) on the 5-point Investigator's Global Assessment Scale. Furthermore, patients' quality of life improved measured by the Dermatology Quality of Life Index and EuroQol 5D index values. The mean time from treatment end to reappearance of visible skin symptoms was 93.8 days (SD: 62.5, range: 31-219 days). Conclusions: Our results confirm that DSC has an immediate effect on skin manifestations and improves quality of life, but long-term disease control is not observed.

Psoriasis is a chronic inflammatory skin disease, in which molecular and cellular changes retain following clinical resolution of psoriatic lesions, a form of disease memory (‘molecular scar’) that may reestablish the psoriatic inflammation. The increasing evidence of the benefits from early intervention in other immune‐mediated diseases prompts the question of whether early systemic intervention, such as biologics, in new‐onset cutaneous psoriasis may lead to improved clinical response and sustained remission by averting an inflammatory disease memory. Herein, we review the current evidence on early intervention and disease memory in psoriasis. The evidence is sparse and inconsistent, although an early intervention within 2 years of disease‐onset may provide a more favourable long‐term prognosis in psoriasis. However, ongoing randomised clinical trials will explore whether early intervention with biologics in new‐onset psoriasis will be an effective treatment strategy, and whether it prevents the molecular and cellular changes potentially underlying the inflammatory disease memory.

Short communication 910 www.medicaljournals.se/acta might be used to objectively quantify lesional areas. In conclusion, this novel method illustrates that psoriasis lesions reappear in a non-random manner, and supports the idea of a molecular scar in psoriasis.