Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

Bachelez, Hervé; Kerkhof, P.C.M. van de; Strohal, Robert; Kubanov, Alexey А.; Valenzuela, Fernando; Lee, Joo Heung; Yakusevich, V. V.; Chimenti, Sergio; Papacharalambous, Jocelyne; Proulx, James; Gupta, Pankaj; Tan, Huaming; Tawadrous, Margaret; Valdez, Hernán; Wołk, Robert

doi:10.1016/s0140-6736(14)62113-9

Cited by 352 publications

(297 citation statements)

References 31 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%

“…Eighteen RCTs compared TNFi (four adalimumab,20, 21, 22, 23, 24 nine etanercept,26, 27, 28, 29, 30, 31, 32, 34, 35 five infliximab36, 37, 38, 39, 40) with placebo, with three studies reporting MACEs; four RCTs compared ustekinumab (anti‐IL‐12/23) with placebo46, 47, 48 with no MACEs reported. One RCT compared ixekizumab with placebo without MACEs reported 56, 57.…”

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%

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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“…L'IL-22 était considérée comme étant la caractéristique des lymphocytes Th17, jusqu'à ce que deux études [49,50] Concernant les inhibiteurs de la signalisation, un essai de phase III évaluant l'efficacité dans le psoriasis en plaques modéré à sévère du tofacitinib, un inhibiteur de JAK (Janus kinase) 1 et JAK3 (des kinases impliquées dans les voies JAK/STAT de signalisation en aval de nombreux récepteurs de cytokines), a montré un effet équivalent de la molécule par rapport au récepteur soluble au TNF-α, l'étanercept, et sa supériorité par rapport au placebo [48].…”

Section: Perspectives : Inhibition De L'interleukine 22unclassified

Immunopathologie du psoriasis

et al. 2016

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> Le psoriasis est une maladie inflammatoire fréquente atteignant essentiellement la peau et parfois les articulations. Cette maladie chronique met rarement en jeu le pronostic vital mais altère significativement la qualité de vie. Le psoriasis est caractérisé, dans sa forme la plus fréquente, par des plaques érythémato-squameuses bien limitées associées à une prolifération exagérée des kératinocytes de l'épiderme, une inflammation et une hypervascularisation du derme superficiel. L'implication des lymphocytes T CD4 de type Th1 a été suspectée initialement. Plus récemment, la découverte du rôle prépondérant des lymphocytes T CD4 de type Th17 dans la maladie a conduit au développement d'inhibiteurs spécifiques de cette voie, tels que les anticorps anti-IL(interleukine)-23 (cytokine favorisant la différenciation des lymphocytes en Th17), anti-IL-17, anti-IL-17RA (récepteur de l'IL-17) et IL-22 (cytokine produite notamment par les lymphocytes Th17). < Structure de la peau humaine normaleLa peau humaine (Figure 1) est constituée de trois couches qui sont, de la profondeur à la superficie, l'hypoderme, le derme et l'épiderme. L'hypoderme est majoritairement constitué des adipocytes qui sont des cellules chargées de lipides. Le derme contient un tissu interstitiel formé de collagène, des vaisseaux sanguins, des annexes piloséba-cées et des cellules du système immunitaire. L'épiderme est constitué de kératinocytes organisés en quatre couches. La plus profonde, la couche basale (stratum basale), est au contact de la membrane basale qui sépare l'épiderme du derme superficiel. Elle est constituée des kératinocytes basaux qui prolifèrent et se différencient en kératinocytes des couches supérieures, c'est-à-dire couche épineuse (stratum spinosum ou corps muqueux de Malpighi), couche granuleuse (stratum granulosum), et couche cornée (stratum corneum) en superficie. Les kératinocytes présents au niveau de la couche cornée (les 1 Inserm U976, laboratoire oncodermatologie, immunologie et cellules souches cutanées, hôpi-tal Saint-Louis,

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“…An oral tablet of tofacitinib dosed as 5 mg or 10 mg twice daily (b.i.d.) was demonstrated to be efficacious for the treatment of moderate to severe psoriasis in four phase III clinical studies 3, 4, 5…”

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confidence: 99%

Quantitative Evaluations of Time‐Course and Treatment Effects of Systemic Agents for Psoriasis: A Model‐Based Meta‐Analysis

Checchio

Ahadieh

Gupta

et al. 2017

Clin Pharma and Therapeutics

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Aggregate data model‐based meta‐analysis is a regression approach to compare the dose–response and/or time‐course across different treatments using summary level data from the literature. Literature search and systematic review following the Cochrane approach yielded 912 sources for investigational and approved treatments for psoriasis. In addition, data for tofacitinib were obtained from an internal database. Tofacitinib is an oral Janus kinase inhibitor. Two mathematical models were developed for Psoriasis Area and Severity Index (PASI) response in moderate to severe psoriasis patients to quantify the time to maximum effect for PASI75 and to evaluate the dose–response relationship for PASI responders (PASI50, PASI75, PASI90, PASI100) at Week 12. Body weight exhibited an inverse effect on the placebo component of both models, suggesting that body weight affects the overall PASI response regardless of drug. This analysis provides a quantitative framework for efficacy comparisons across psoriasis treatments.

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Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

Cited by 352 publications

References 31 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

Immunopathologie du psoriasis

Quantitative Evaluations of Time‐Course and Treatment Effects of Systemic Agents for Psoriasis: A Model‐Based Meta‐Analysis

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