Ustekinumab therapy changes the transcriptional activity
pattern of TGF-β1–3 genes

Grabarek, Beniamin Oskar; Wcisło‐Dziadecka, Dominika; Strzałka‐Mrozik, Barbara; Gola, Joanna; Plewka, Andrzej

doi:10.5114/ada.2019.91504

Cited by 4 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, De Keyser et al ( 19 ) study and Van Vugt et al ( 24 ) meta-analysis conclude that there is no justification for excluding patients with negative HLA-C*06 for ustekinumab treatment. Analyzing the expression patterns of the TGF-β gene and transcription activity profiles of TNF-α, TNFR1, and TNFR2 may also be useful for monitoring ustekinumab therapy ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

et al. 2022

View full text Add to dashboard Cite

IntroductionThere is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting.MethodsObservational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI > 3). Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value < 0.05 was considered statistically significant.ResultsA total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 μg/mL (range <0.1–1.8) vs. 0.4 μg/mL (range <0.1–0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 μg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders.ConclusionA positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.

show abstract

Section: Discussionmentioning

confidence: 99%

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Another report with equivalent outcomes observes that TGF-β1 signaling has been markedly inhibited by fluoroquinolone chemotherapy . However, several antipsoriatic therapies, including ustekinumab, apremilast, and acitretin, apparently accomplish their healing benefits by inhibiting the TGF-β regulatory pathways. − Also noteworthy is that fluoroquinolones inhibit TGF-β-stimulating mechanisms, preventing cells from traveling and invasion. Fluoroquinolones may stop TGF-β biosynthesis by increasing the amount of endoplasmic cAMP and blocking TGF-β receptors …”

Section: Discussionmentioning

confidence: 99%

Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis

Ridha-Salman,

Shihab,

Hasan

et al. 2024

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Psoriasis is a chronic, inflammatory dermatosis characterized by thickened, reddened, and scaly skin lesions. Norfloxacin is a fluoroquinolone antibiotic with enhanced antioxidant, anti-inflammatory, and immunomodulatory bioactivities. The aim of this study was to figure out the possible impact of topical norfloxacin on an imiquimod-induced model of psoriasis in mice. Thirty albino-type mice were split into five distinct groups of six animals each. The control group included healthy mice that had not received any treatment. The induction group was given the vehicle 2 h after the topical imiquimod, once daily for 8 days. Two hours after receiving topical imiquimod, the treatment groups including calcipotriol, norfloxacin 2.5%, and norfloxacin 5% were given topical ointments containing calcipotriol 0.005%, norfloxacin 2.5%, and norfloxacin 5%, for 8 days. Topical norfloxacin ointment significantly reduced the severity of imiquimod-exacerbated psoriatic lesions including erythema, shiny-white scaling, and acanthosis and fixed histological abnormalities. Furthermore, imiquimod-subjected mice treated with a higher concentration of norfloxacin ointment exhibited dramatically lower skin levels of inflammation-related biomarkers like IFN-γ, TNF-α, IL-6, IL-17A, IL-23, and TGF-β but higher levels of IL-10. They also demonstrated a notable decrease in angiogenesis parameters such as VEGF and IL-8, a substantial reduction in oxidative indicators like MDA and MPO, and a considerable rise in antioxidant enzymes like SOD and CAT. This study offers novel evidence that norfloxacin may assist in controlling inflammatory dermatoses like psoriasis by minimizing the severity of psoriatic plaques, correcting histological alterations, and diminishing the production of inflammatory, oxidative, and angiogenetic parameters.

show abstract

“…Another noteworthy study analyzed the effect of ustekinumab on serum levels of active TGF-β1, showing an overall decrease in serum levels after 28 weeks of therapy ( 18 ). This may have contributed to our patient’s improved clinical response and controlled CED-associated bone pain, assuming the proinflammatory role of TGF-β1 signaling in the gut.…”

Section: Discussionmentioning

confidence: 99%

Dual Biologic Therapy in an Adolescent With Camurati-Engelmann Disease and Crohn Disease

Sami

Rosh

2022

JPGN Reports

View full text Add to dashboard Cite

Camurati-Engelmann disease (CED) is a rare disorder caused by activating mutations in the TGF-β1 gene and characterized by hyperostosis of long bones and bone dysplasia. We describe a case of an adolescent with CED and moderate-severe Crohn Disease (CD). Infliximab improved gastrointestinal symptoms but was associated with worsening CED-associated bone pain. Clinical remission was successfully achieved with dual biologic therapy that included vedolizumab and ustekinumab. Possible reasons for this patient's clinical response are advanced and include speculation about the complex role of TGF-β1 signaling in the etiology of both CED and CD.

show abstract

Ustekinumab therapy changes the transcriptional activity pattern of TGF-β1–3 genes

Cited by 4 publications

References 23 publications

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis

Dual Biologic Therapy in an Adolescent With Camurati-Engelmann Disease and Crohn Disease

Contact Info

Product

Resources

About