Combined Use of Systemic Agents for Psoriasis

Busard, C.; Zweegers, Jeffrey; Limpens, Jacqueline; Langendam, Miranda; Spuls, Phyllis I.

doi:10.1001/jamadermatol.2014.1111

Cited by 39 publications

(32 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phototherapy, involving exposure to UVA or UVB light alone or in combination with a photosensitizer, is recommended for moderate-to-severe psoriasis [14]. Systemic medications, including methotrexate, cyclosporine, acitretin, azathioprine, and sulfasalazine, are used to treat psoriasis that is too extensive for, or refractory to, topical or UV therapy [15, 16]. However, these medications have significant dose-limiting toxicities.…”

Section: Introductionmentioning

confidence: 99%

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

et al. 2017

View full text Add to dashboard Cite

BackgroundDalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis.ObjectiveThe primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations.MethodsPatients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires.ResultsThe most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells.LimitationsThe study was small and drug treatment was for a short duration (4 weeks).ConclusionThis study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.

show abstract

Section: Introductionmentioning

confidence: 99%

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Methotrexate (MTX) is an effective therapeutic modality for treatment of a variety of inflammation-based disorders, such as rheumatoid arthritis, juvenile arthritis, lupus, psoriatic arthritis, myositis, vasculitis, and even some inflammatory gastrointestinal disorders, such as inflammatory bowel disease (1,2). Regardless of its high efficacy, organic and metabolic toxicity of MTX is also considerable in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Transient Elastography in Methotrexate Administered Patients

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Fumarates have also been used in combination with other systemic agents such as cyclosporin, acitretin, hydroxyurea and MTX [27]. However, no prospective randomized clinical trials were performed to evaluate the efficacy and safety of these combinations [28]. …”

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

View full text Add to dashboard Cite

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.

show abstract

Combined Use of Systemic Agents for Psoriasis

Cited by 39 publications

References 32 publications

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

Transient Elastography in Methotrexate Administered Patients

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

Contact Info

Product

Resources

About