Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)

Papp, Kim; Langley, Richard; Lebwohl, Mark; Krueger, Gerald G.; Szapary, Philippe; Yeilding, Newman; Guzzo, Cynthia; Hsu, Mei‐Chich; Wang, Yuhua; Li, Shu; Dooley, Lisa T.; Reich, Kristian

doi:10.1016/s0140-6736(08)60726-6

Cited by 1,298 publications

(1,318 citation statements)

References 19 publications

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“…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%

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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

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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.

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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

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“…Erythema (redness): diameter (mm) and severity from none to severe (0 = none, 1= mild, 2 = moderate 3 = severe) Swelling/Induration: diameter (mm) and severity from none to severe (0 = none, 1= mild, 2 = moderate 3 = severe) Hematoma: yes/ no and if present diameter (mm) Local pain -assessed by the study subject on a visual analogue scale (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) Refer to appendix K Pruritus -assessed by the study subject on a visual analogue scale (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) Refer to appendix L …”

Section: Local Tolerance and Tolerabilitymentioning

confidence: 99%

“…In 2014, the World Health Organisation recognized psoriasis as a serious non-communicable disease and its report from 2016 highlighted the life running nature of the disease and the need to urgently research and make accessible cost effective medicines throughout the world. 1 The development of monoclonal antibodies that target cytokines central to the psoriatic disease cascade including TNF, IL-23, and IL-17A, has significantly broadened the therapeutic armamentarium [2][3][4] however, recent surveys indicate restricted usage of these expensive therapies in less than 10% of patients with moderate-to-severe disease even in Western countries. 5 For over 50 year's methotrexate (MTX) has been used in the treatment of psoriasis and psoriatic arthritis and is recommended as first-line systemic agent for the treatment of moderate-to-severe psoriasis in US and European guidelines 6 mainly based on experience and health economic considerations.…”

Section: Introductionmentioning

confidence: 99%

An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Warren

Mrowietz

Kiedrowski³

et al. 2017

The Lancet

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Background: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-tosevere psoriasis. Methods: In this prospective, double-blind, multicentre phase 3 study (METOP) eligible patients were 18 years or older with a diagnosis of chronic plaque psoriasis at least 6 months before baseline, had a psoriasis area and severity index (PASI) of 10 or more or 10% or greater body-surface area involvement or a dermatology life quality index (DLQI) of 10 or more and were naïve to treatment with MTX. Participants were randomly assigned 3:1 by computer-generated random sequence integrated in the electronic data capture system to receive either MTX at a starting dose of 17.5 mg/week or placebo for the first 16 weeks, followed by openlabel MTX treatment of all patients up to 52 weeks (MTX/MTX and PLC/MTX groups, respectively). Dose escalation to 22.5 mg/week was allowed after 8 weeks of MTX therapy if patients failed to achieve an at least 50% improvement of their baseline PASI (PASI50); blinding was maintained by a corresponding volume increase of placebo injections. Treatment was combined with folic acid 5 mg/week. The primary efficacy endpoint was the proportion of patients achieving a PASI75 response at week 16 analysed by intention to treat with non-responder imputation. This study is registered with the European Medicines Agency, EudraCT number 2012-002716-10. Findings: Between February 2013 and May 2015 120 patients were randomly assigned to receive subcutaneous MTX (n=91) or placebo (n=29). The primary endpoint was met; the PASI75 response rate at week 16 was 41% (n=37) in the MTX group compared to 10% (n=3) in the placebo group [p=0.0026; effect size 30.3% (95% CI 15.3-45.3) MTX vs placebo]. Subcutaneous MTX was generally well tolerated; no cases of serious infections, malignancies, major adverse cardiovascular events or deaths were noted. Serious adverse events were observed in 3 patients started on MTX during the 52-week study period. Interpretation: The study documents a favourable 52-week benefit-risk profile of subcutaneous MTX in psoriasis. The route of administration and the intensified dosing schedule should be considered when using MTX in patients with psoriasis. Role of the funding source (see also below)The study was an investigator-initiated trial supported by a grant from Medac to K.R. Manuscript 2 SummaryBackground: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-to-severe psoriasis.

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“…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: 64%

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

Kerdel

Zaiac

2015

Dermatologic Therapy

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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.

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Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)

Cited by 1,298 publications

References 19 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 intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

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

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