What's new about the mechanism of methotrexate action in psoriasis?

Chen, Z.

doi:10.1111/bjd.16908

Cited by 7 publications

(7 citation statements)

References 10 publications

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“…The potential value of concurrent MTX has yet to be determined. 23 Despite the relatively high rate of AEs (27%), secukinumab was well tolerated providing an acceptable safety profile. We note with interest the 10 cases of new-onset, or exacerbation of, dyslipidaemia reported over the study period.…”

Section: Discussionmentioning

confidence: 98%

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Real‐world data from a single Greek centre on the use of secukinumab in plaque psoriasis: effectiveness, safety, drug survival, and identification of patients that sustain optimal response

Rompoti

Sidiropoulou

Panagakis

et al. 2020

Acad Dermatol Venereol

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Background Few studies have investigated the long-term outcomes of secukinumab in real-life psoriasis treatment where diverse patient profiles require a personalized approach. Objectives To determine long-term performance of secukinumab in moderate-to-severe plaque psoriasis, and identify potential clinical factors predictive of sustained optimal response under real-world conditions. Methods In this 78-week, single-centre, retrospective study, effectiveness, safety and drug survival of secukinumab were evaluated. Effectiveness data are reported as observed. Co-primary endpoints were absolute Psoriasis Area and Severity Index (PASI) ≤3 at week 4, 16, 52, 78, and clinical predictors of PASI ≤3 and PASI100 responses at week 52 and 78. Results A total of 85 patients (75.3% male; mean age 48.6 years) were included. Absolute PASI ≤3 was achieved in 73% and 83% of patients at week 52 and 78, respectively. PASI 75/90/100 responses at week 52 (71.6%, 50.8%, and 40.3%, respectively) were sustained at week 78 (73.6%, 64.2%, and 45.3%, respectively). Median absolute PASI remained low at week 52/78 (0.9/0.6, respectively), while mean absolute PGA also sustained low (0-1) values after 16-78 weeks. Investigator's Global Assessment 0/1 response rate was maintained by week 52/78 (72/83%, respectively). The drug survival rate of secukinumab at week 78 was 79.1%. Treatment was discontinued in 17.9% of patients after an average of 41.7 weeks, mainly due to loss of effectiveness (10.4%). A total of 27% experienced adverse events, without critical safety concerns. Based on multivariate analysis, advanced body mass index (BMI) and presence of ≥3 comorbidities decreased the chance of achieving PASI ≤3 at week 78 [OR (95% CI) 0.78 (0.64-0.97); P = 0.024, and OR (95% CI) 0.045 (0.002-0.83); P = 0.037, respectively]. Conclusions Secukinumab showed consistently high effectiveness in this real-life cohort, with an acceptable safety profile. Over time, persistence of PASI ≤3 response appears to be lower in patients with high BMI or multiple comorbidities.

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Section: Discussionmentioning

confidence: 98%

“…We empirically recommend the use of MTX in doses of 7.5–15 mg/week. The potential value of concurrent MTX has yet to be determined …”

Section: Discussionmentioning

confidence: 99%

Real‐world data from a single Greek centre on the use of secukinumab in plaque psoriasis: effectiveness, safety, drug survival, and identification of patients that sustain optimal response

Rompoti

Sidiropoulou

Panagakis

et al. 2020

Acad Dermatol Venereol

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“…MTX exercises its anti‐inflammatory effects by reducing recruitment of inflammatory cells and increasing apoptosis of activated T cells 30–35 . It also reduces synthesis of purines, pyrimidines, DNA and RNA by inhibiting thymidylate synthase activity 36 .…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐9 serves as a key link between systemic inflammation and angiogenesis in psoriasis

Midde

Priyadarssini

Rajappa

et al. 2020

Clin Experimental Derm

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Background. Psoriasis is a T helper cell-mediated chronic immune-mediated inflammatory disease affecting mainly the skin, although systemic pathological effects are also observed. Cytokine-mediated interaction between T lymphocytes and keratinocytes lead to excessive proliferation of keratinocytes, which in turn leads to formation of a proinflammatory milieu and finally to psoriatic plaque formation. Aim. To measure interleukin (IL)-9, IL-17 and vascular endothelial growth factor (VEGF) levels in patients with psoriasis compared with controls, and to evaluate the effect of methotrexate (MTX) monotherapy on the aforesaid cytokine levels in psoriasis. Methods. This cohort study included 54 patients with psoriasis and 54 age-and sex-matched healthy controls (HCs). IL-9, IL-17 and VEGF levels were measured by using commercially available ELISA kits. Patients with psoriasis who were on MTX monotherapy were followed up for a period of 3 months. Results. Patients with psoriasis had increased levels of IL-9, IL-17 and VEGF at baseline, compared with the HC group. After 3 months of MTX monotherapy, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI) and levels of cytokines (IL-9, IL-17 and VEGF) were significantly decreased compared with baseline. PASI and DLQI at baseline also showed a positive correlation with IL-9, IL-17 and VEGF. Conclusion. Our results suggest the existence of a proinflammatory milieu in psoriasis, with increased levels of IL-9, IL-17 and the proangiogenic growth factor VEGF, showing an increasing trend with increasing disease severity and impaired quality of life (QoL). MTX treatment helps to reduce levels of IL-9, IL-17 and VEGF, thereby limiting disease progression and improving QoL in psoriasis.

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“…Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties which includes anti-aging ( Bukhari et al., 2018 ), anti-inflammatory ( Chen, 2018 ), skin repairing ( Narurkar et al., 2016 ), tissue regeneration ( Bukhari et al., 2018 ) and wound recovery properties ( Chen, 2018 ). HA possess good biocompatibility, high moisture retention, and tuneable viscoelastic properties ( Sze et al., 2016 ).…”

Section: Structural and Functional Characteristics Of Hyaluronic Acidmentioning

confidence: 99%

“…Methotrexate, an analogue of folic acid has been used as a drug to treat psoriasis skin condition ( Czarnecka-Operacz and Sadowska-Przytocka, 2014 ). Methotrexate has been shown to down-regulate interleukin-17 and interferon-c, inhibit proliferation of effector T cells and restore the immunosuppressive function of regulatory T cells ( Chen, 2018 ). Nevertheless, its high molecular weight, hydrophilicity and inability to maintain a stable form at physiological pH restricted the permeability of methotrexate by passive diffusion through the stratum corneum ( Alvarez-Figueroa et al., 2001 ).…”

Section: Ha As a Drug Delivery System In Psoriasismentioning

confidence: 99%

Hyaluronic Acid-Mediated Drug Delivery System Targeting for Inflammatory Skin Diseases: A Mini Review

et al. 2020

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Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties. Various types of HA drug delivery system including nanoparticles, cryogel-based formulations, microneedle patches, and nano-emulsions were developed. There are studies reporting that several HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability and efficient localized release of anti-psoriasis drugs and have shown to inhibit psoriasis-associated skin inflammation. Similarly HA is found in abundant at epidermis of atopic dermatitis (AD) suggesting its role in atopic AD pathology. Anti-allergenic effect of atopic eczema can be achieved through the inhibition of CD44 and protein kinase C alpha (PKCa) interaction by HA. Herein, we aim to evaluate the current innovation on HA drug delivery system and the other potential applications of HA in inflammatory skin diseases, focusing on atopic dermatitis and psoriasis. HA is typically integrated into different delivery systems including nanoparticles, liposomes, ethosomes and microneedle patches in supporting drug penetration through the stratum corneum layer of the skin. For instance, ethosomes and microneedle delivery system such as curcumin-loaded HA-modified ethosomes were developed to enhance skin retention and delivery of curcumin to CD44-expressing psoriatic cells whereas methotrexate-loaded HA-based microneedle was shown to enhance skin penetration of methotrexate to alleviate psoriasis-like skin inflammation. HA-based nanoparticles and pluronic F-127 based dual responsive (pH/temperature) hydrogels had been described to enhance drug permeation through and into the intact skin for AD treatment.

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What's new about the mechanism of methotrexate action in psoriasis?

Abstract: Linked Article: Yan et al. Br J Dermatol 2018; 179:896–905.

Cited by 7 publications

References 10 publications

Real‐world data from a single Greek centre on the use of secukinumab in plaque psoriasis: effectiveness, safety, drug survival, and identification of patients that sustain optimal response

Real‐world data from a single Greek centre on the use of secukinumab in plaque psoriasis: effectiveness, safety, drug survival, and identification of patients that sustain optimal response

Interleukin‐9 serves as a key link between systemic inflammation and angiogenesis in psoriasis

Hyaluronic Acid-Mediated Drug Delivery System Targeting for Inflammatory Skin Diseases: A Mini Review

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