Search

Background Secukinumab is effective against a range of psoriatic manifestations. Investigating psoriasis (PsO) relapse following secukinumab discontinuation could provide insights into long-term PsO remission. Objectives To examine PsO relapse rates on treatment discontinuation following 1 year of secukinumab treatment. Methods This study (clinical trial number: NCT01544595) is an extension of the phase III ERASURE/FIXTURE studies in patients with moderate-to-severe plaque PsO. After 1 year of secukinumab 300 mg or 150 mg treatment, participants who had responded to treatment with a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) at week 52 were randomly assigned to receive placebo (n = 120 and n = 100, respectively). On relapse, patients receiving placebo were switched to their previous secukinumab dose. The study primary outcome was the nonrelapse rate after secukinumab withdrawal. Results Following the last dose of secukinumab 300 mg, 20.8% (25/120) and 10.0% (12/120) of patients who switched to placebo did not relapse at 1 and 2 years after discontinuation, respectively. Patients who received secukinumab 150 mg for 1 year showed a lower proportion of nonrelapse following treatment discontinuation [14% (14/100) and 6% (6/100)] at 1 and 2 years, respectively. Patients who did not relapse maintained low mean PASI (2.8) at 1 year drug free vs. baseline (20.9); 1.7 at 2 years drug free vs. baseline (19.2), following an initial 52-week treatment with secukinumab 300 mg. Disease duration (P = 0.02) and severity (P = 0.02) were significantly associated with time to relapse in patients initially treated with secukinumab 300 mg; patients with shorter disease duration and lower baseline PASI remained relapse-free for longer. Conclusions Following discontinuation of secukinumab, a proportion of patients stayed relapse-free. Further, patients with shorter disease duration remained relapse-free for longer, suggesting that earlier treatment with secukinumab may result in long-term clinical control of moderate-to-severe PsO. [ABSTRACT FROM AUTHOR]

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory. [ABSTRACT FROM AUTHOR]

This article discusses the price variability of TNF-α inhibitor biosimilars for the treatment of psoriasis across European countries. The study found that there is significant price variability, with lower prices in Italy and Spain compared to Germany, France, and Denmark. The pricing policies adopted by different countries, such as mandatory discounts, progressive price discounts, and tendering or direct contracting, contribute to this variability. The findings highlight the potential impact on healthcare costs and patient access to biological treatment. However, it is important to note that the study only included one center per country. [Extracted from the article]

Background: Heat shock protein 90 (HSP90) is an important chaperone supporting the function of many proinflammatory client proteins. Recent studies indicate HSP90 inhibition may be a novel mechanism of action for inflammatory skin diseases; however, this has not been explored in atopic dermatitis (AD). Objectives: Our study aimed to investigate HSP90 as a novel target to treat AD. Methods: Experimental models of AD were used including primary human keratinocytes stimulated with cytokines (TNF/IFNg or TNF/IL-4) and a mouse model established by MC903 applications. Results: In primary human keratinocytes using RT-qPCR, the HSP90 inhibitor RGRN-305 strongly suppressed the gene expression of Th1-(TNF, IL1B, IL6) and Th2-associated (CCL17, CCL22, TSLP) cytokines and chemokines related to AD. We next demonstrated that topical and oral RGRN-305 robustly suppressed MC903-induced AD-like inflammation in mice by reducing clinical signs of dermatitis (oedema and erythema) and immune cell infiltration into the skin (T cells, neutrophils, mast cells). Interestingly, topical RGRN-305 exhibited similar or slightly inferior efficacy but less weight loss compared with topical dexamethasone. Furthermore, RNA sequencing of skin biopsies revealed that RGRN-305 attenuated MC903-induced transcriptome alterations, suppressing genes implicated in inflammation including AD-associated cytokines (Il1b, Il4, Il6, Il13), which was confirmed by RT-qPCR. Lastly, we discovered using Western blot that RGRN-305 disrupted JAK-STAT signaling by suppressing the activity of STAT3 and STAT6 in primary human keratinocytes, which was consistent with enrichment analyses from the mouse model. Conclusion: HSP90 inhibition by RGRN-305 robustly suppressed inflammation in experimental models mimicking AD, proving that HSP90 inhibition may be a novel mechanism of action in treating AD. [ABSTRACT FROM AUTHOR]