Combining Biologic Therapies With Other Systemic Treatments in Psoriasis

Armstrong, April W.; Bagel, Jerry; Voorhees, Abby S. Van; Robertson, Andrew D.; Yamauchi, Paul S.

doi:10.1001/jamadermatol.2014.3456

Cited by 60 publications

(17 citation statements)

References 44 publications

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“…Biologic agents have been approved by the FDA to treat moderate to severe psoriasis that not responded to an adequate trial of one or more of the traditional drugs. Biologic therapies are most effective in the treatment of psorisis [32], but a percentage of no-responder patients still exists. Moreover, disadvantages are represented by their possible side effects and limited availability of long-term safety data.…”

Section: Introductionmentioning

confidence: 99%

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Bessar

Venditti

Benassi

et al. 2016

Colloids and Surfaces B: Biointerfaces

118

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a b s t r a c tGold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Watersoluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24 h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24 h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that these layers of the skin do not retain the nanoparticles. Based on our data, we found that the novel Au-3MPS@MTX conjugate is an effective non-toxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis.

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Section: Introductionmentioning

confidence: 99%

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Bessar

Venditti

Benassi

et al. 2016

Colloids and Surfaces B: Biointerfaces

118

View full text Add to dashboard Cite

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“…In daily practice MTX is more frequently combined with biologics than fumarates, because it is assumed that (low-dose) MTX increases the clinical efficacy of biologics by reducing the development of antidrug antibodies [23,24]. Anti-etanercept antibodies have only sporadically been observed in clinical studies, indicating that loss of clinical efficacy for etanercept is probably caused by other, yet unidentified factors [25].…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Bezooijen¹,

Balak²,

Doorn³

et al. 2016

Dermatology

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Background: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.

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“…In fact, data from recent European reports indicate that biological therapy is given concomitantly with traditional systemic drugs in up to 30% of patients with psoriasis . Combination therapy of ciclosporin A with biological drugs, particularly etanercept and adalimumab, has been rarely reported in the literature, including in nonrandomized trials and case reports . However, in a review of the literature we found no studies reporting combination therapy of ciclosporin A and infliximab, except for short overlapping periods during switching or sequential therapy…”

Section: Main Patient Characteristics At Baseline and During Follow‐upmentioning

confidence: 93%

Combination therapy of infliximab and ciclosporin in the treatment of recalcitrant psoriasis: a case series

et al. 2017

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Combining Biologic Therapies With Other Systemic Treatments in Psoriasis

Abstract: Among appropriately selected patients with psoriasis, carefully chosen combinations may result in greater efficacy, while minimizing toxicity.

Cited by 60 publications

References 44 publications

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Combination therapy of infliximab and ciclosporin in the treatment of recalcitrant psoriasis: a case series

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