Pustulotic arthro-osteitis (PAO) is a significant comorbidity of palmoplantar pustulosis (PPP), with biologics targeting tumor necrosis factor (TNF)-α, interleukin (IL)-12/23 p40, IL-23 p19, and IL-17 showing clinical benefits for PPP/PAO. However, patients receiving these biological agents frequently experience paradoxical skin reactions (PSRs), particularly with anti-TNF-α treatments. We report a case of PPP/PAO treated with the anti-TNF-α agent adalimumab, which led to the development of PSRs, including psoriasis-like and folliculitis-like rashes, and acute hair loss. Subsequently, treatment was changed to guselkumab, an anti-IL-23 p19 monoclonal antibody, which successfully controlled both PPP/PAO and PSRs. To date, no PSRs associated with anti-IL-23 agents in PAO have been reported. A study from Japan indicates that guselkumab and adalimumab have similar efficacy in treating PAO. Given that anti-IL-23 agents are approved for refractory PPP under the Japanese health insurance system, we recommend their use over adalimumab in PPP/PAO patients to prevent PSRs.

2015-05-04·Chembiochem : a European journal of chemical biology4区 · 生物学

Antimicrobial Peptides from the Aurein Family Form Ion‐Selective Pores in Bacillus subtilis

4区 · 生物学

Article

作者: Senges, Christoph Helmut Rudi ; Raatschen, Nadja ; Kumar, Prashant ; Stepanek, Jennifer Janina ; Nguyen, Michael ; Suleman, Selina ; Chiriac, Alina Iulia ; Zhang, Jin ; Bandow, Julia Elisabeth ; Straus, Suzana Katarina ; Kraemer, Ute ; May, Caroline ; Wenzel, Michaela ; Sahl, Hans-Georg

Abstract:

The mechanism of action of aurein 2.2 and aurein 2.3, antimicrobial peptides from the frog Litoria aurea, was investigated. Proteomic profiling of the Bacillus subtilis stress response indicates that the cell envelope is the main target for both aureins. Upon treatment, the cytoplasmic membrane depolarizes and cellular ATP levels decrease. Global element analysis shows that intracellular concentrations of certain metal ions (potassium, magnesium, iron, and manganese) strongly decrease. Selective translocation of some ions over others was demonstrated in vitro. The same set of ions also leaks from B. subtilis cells treated with sublethal concentrations of gramicidin S, MP196, and nisin. Aureins do not permeabilize the cell membrane for propidium iodide thus excluding formation of large, unspecific pores. Our data suggest that the aureins acts by forming small pores thereby causing membrane depolarization, and by triggering the release of certain metal ions thus disturbing cellular ion homeostasis.

Dermatology and Therapy

Real-World Benefit of Tildrakizumab for Moderate-to-Severe Plaque Psoriasis: Findings from a Systematic Literature Review and Meta-Analysis

Review

作者: Bhatia, Neal ; Lam, Otto ; Barghout, Victoria ; Farberg, Aaron S ; Mathew, Jacob ; Fazeli, Mir Sohail ; Ferro, Thomas J ; Hofer, Kimberly ; Gottlieb, Scott

INTRODUCTION:

Plaque psoriasis (PsO) is an inflammatory skin disease that can impair quality of life. Tildrakizumab, an anti-IL-23 p19 monoclonal antibody, offers a treatment option for patients eligible for systemic therapy or phototherapy, but real-world results have not been comprehensively analyzed. This systematic review and meta-analysis evaluated real-world effectiveness, quality-of-life impact, and safety of tildrakizumab for treatment of moderate-to-severe plaque PsO, alone and relative to guselkumab and risankizumab.

METHODS:

MEDLINE® and Embase were searched on November 16, 2023, along with meeting abstracts (2021-2023) and bibliographies of previous reviews, for English-language real-world studies of tildrakizumab (singly or comparative) in adults with chronic moderate-to-severe plaque PsO. Outcomes included effectiveness (Psoriasis Area and Severity Index [PASI], Physician's Global Assessment [PGA], body surface area percentage [%BSA] affected), Dermatology Life Quality Index (DLQI), and safety (adverse events [AEs], serious AEs [SAEs], treatment-related AEs [TRAEs], or withdrawals due to AEs [WDAEs]). Meta-analyses were performed at 12-16, 24-28, and 36-52 weeks.

RESULTS:

Of 6982 records screened, 37 studies (45 publications) were analyzed. Tildrakizumab-treated patients experienced 78-87% improvement from baseline to 36-52 weeks across mean absolute PASI (12.81 [95% confidence interval 11.69, 13.92] to 1.62 [1.03, 2.20]), %BSA (16.21% [13.72%, 18.70%] to 3.27% [1.26%, 5.28%]), PGA (3.18 [2.89, 3.47] to 0.70 [0.08, 1.33]), and DLQI (14.59 [12.32, 16.87] to 1.83 [0.84, 2.82]), with low rates of AEs, SAEs, TRAEs, and WDAEs. Benefits and safety of tildrakizumab were similar to guselkumab and risankizumab.

CONCLUSION:

Tildrakizumab demonstrated effectiveness, with reduction from moderate-to-severe to mild disease and improved DLQI scores, without notable safety concerns, for up to 1 year in this real-world meta-analysis. Although real-world data must be interpreted cautiously because of heterogeneity and potential bias, these findings align with randomized trial results, further supporting the use of tildrakizumab in clinical practice.

100 项与 MP-196 相关的药物交易

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