Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)

Leonardi, Craig L.; Kimball, Alexa B.; Papp, Kim; Yeilding, Newman; Guzzo, Cynthia; Wang, Yuhua; Li, Shu; Dooley, Lisa T.; Gordon, Kenneth B.

doi:10.1016/s0140-6736(08)60725-4

Cited by 1,571 publications

(1,419 citation statements)

References 34 publications

Supporting

Mentioning

1,267

Contrasting

Unclassified

Order By: Relevance

“…In all, 38 RCTs (identified in 38 reports)20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 met the eligibility criteria and were included, as shown in Figure 1. These trials involved a total of 18 024 patients with plaque psoriasis.…”

Section: Resultsmentioning

confidence: 99%

“…Patients in 27 RCTs20, 21, 22, 25, 27, 28, 29, 30, 31, 34, 35, 36, 37, 38, 39, 40, 43, 45, 46, 47, 48, 50, 52, 53, 57 did not experience MACEs while exposed to any interventions but 10 MACEs were observed during the randomized controlled phase of nine studies 23, 26, 32, 33, 42, 44, 49, 51. Overall, the pooled analysis of these nine trials found that there was no statistically significant difference in the risk of MACEs when comparing biologic therapies with placebo (pooled OR 1·45, 95% CI 0·34–6·24, P = 0·62), as shown in Figure 2a.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials

et al. 2017

View full text Add to dashboard Cite

SummaryConcerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I 2 statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Results from these studies support that switching to ustekinumab is effective and well tolerated for most patients, given the high overall PASI 75 response rates at week 12 (67.1% with the 45‐mg dose in PHOENIX 1 and 66.7% with the 45‐mg dose in PHOENIX 2) and acceptable safety profile of ustekinumab 68, 69. Similarly, in the phase 3 ERASURE and FIXTURE studies of the IL‐17A antibody, secukinumab, 12.5–29.3% of patients had psoriasis that was poorly controlled with previous a biologic therapy (anti‐TNFα or ustekinumab), with up to 7.6% of patients experiencing no response to previous anti‐TNFα therapy 15.…”

Section: Published Literature Evaluating Switching Psoriasis Treatmentsmentioning

confidence: 68%

An evolution in switching therapy for psoriasis patients who fail to meet treatment goals

Kerdel

Zaiac

2015

Dermatologic Therapy

View full text Add to dashboard Cite

Switching psoriasis treatment is a common, accepted practice that is used to improve disease management and improve patient outcomes (e.g., when patients are experiencing suboptimal efficacy and/or tolerability with a given therapy). Historically, switching treatment was often performed to limit patients’ cumulative exposure to conventional systemic agents (e.g., methotrexate, cyclosporine) with the goal of reducing end‐organ toxicity. However, the practice of switching treatments has evolved in recent years with the availability of highly effective and tolerable biologic agents. In current practice, near‐complete skin clearance with minimal side effects should be a realistic treatment goal for most patients with moderate‐to‐severe psoriasis, and consideration for switching therapies has shifted to become more focused on achieving maximum possible skin clearance, enhanced quality of life, and improved patient satisfaction. This review provides a discussion of recent guidance on switching psoriasis therapies, including initial considerations for when switching therapy may be advisable and challenges associated with switching therapy, along with an overview of published clinical studies evaluating outcomes associated with switching therapy. The goal of this review is to empower dermatologists to optimally manage their patients’ psoriasis by providing the tools needed to develop rational strategies for switching treatments based on the pharmacologic characteristics of available treatments and each patient's clinical needs and treatment preferences.

show abstract

“…Indeed, IL-23 injection into normal skin was sufficient for the development of psoriatic phenotypes in mice 50,51 , and a monoclonal antibody against IL-12/23p40 subunit, ustekinumab is efficacious for the treatment of patients with moderate-to-severe psoriasis 52 . Although cKO skin shared some molecular features of psoriasis, it did not demonstrate all the histological characteristics of psoriatic skin.…”

Section: Discussionmentioning

confidence: 99%

Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice

et al. 2012

View full text Add to dashboard Cite

Phospholipase C is a key enzyme in phosphoinositide turnover. Although its functions have been extensively studied at the cellular level, many questions remain concerning its functions at the organ and individual animal levels. Here we demonstrate that mice lacking phospholipase Cδ1 develop granulocytosis associated with elevated serum levels of the granulopoietic cytokine interleukin-17. Re-introduction of phospholipase Cδ1 into keratinocytes of phospholipase Cδ1-deficient mice reverses this phenotype, whereas conditional ablation of phospholipase Cδ1 in keratinocytes recreates it. Interleukin-17 and its key upstream regulator interleukin-23 are also upregulated in epidermis. Loss of phospholipase Cδ1 from keratinocytes causes features of interleukin-17-associated inflammatory skin diseases. Phospholipase Cδ1 protein is downregulated in the epidermis of human psoriatic skin and in a mouse model of psoriasis. These results demonstrate that phosphoinositide turnover in keratinocytes regulates not only local inflammatory responses but also serum cytokine levels and systemic leukocyte counts, and affects distant haematopoietic organs.

show abstract

Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)

Cited by 1,571 publications

References 34 publications

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials

An evolution in switching therapy for psoriasis patients who fail to meet treatment goals

Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice

Contact Info

Product

Resources

About