The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: A Phase 3, randomized, double-blind, placebo-controlled study

Zhang, Jianzhong; Tsai, Tsen‐Fang; Lee, Min Geol; Zheng, Min; Wang, Gang; Jin, Hong; Gu, Jun; Li, Ruo Yu; Liu, Quan-Zhong; Jin, Cheqing; Tu, Cai Xia; Qi, Chun Mei; Zhu, Hua; Ports, William C.; Crook, Tim

doi:10.1016/j.jdermsci.2017.05.004

Cited by 69 publications

(50 citation statements)

References 30 publications

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“…The standard efficacy target for new biological treatments for psoriasis is PASI90, as seen in up to 60-70% of patients [3,22]. For the highest dose of BMS-986165 tested, PASI90 was 43% [16]. Accordingly, current data do not indicate that new JAK inhibitors, including TYK2 inhibitors, will outperform the newest biologics.…”

Section: Discussionmentioning

confidence: 89%

“…The selective TYK2 inhibitor BMS-986165 has shown the highest efficacy towards psoriasis of any JAK inhibitor to date, with a PASI75 response of 75% after 12 weeks of treatment in a phase 2 trial [17]. Tofacitinib is the most studied JAK inhibitor for the treatment of psoriasis, with four reported phase 3 trials showing considerable efficacy in terms of the PASI75 response, especially at a high dose of 10 mg twice daily [13][14][15][16]. Other JAK inhibitors have also been tested for psoriasis; these have yielded PASI75 responses that are less than or similar to that achieved with tofacitinib.…”

Section: Discussionmentioning

confidence: 99%

“…Across the phase 3 studies, tofacitinib had efficacies of 39.5-54.3% (5 mg [13][14][15][16]. The highest PASI75 responses at both dosages were observed in an Asian population [16]. These studies also showed the clinical efficacy of tofacitinib for secondary end points such as the Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index (NAPSI), and PASI90 compared to placebo.…”

Section: Tofacitinib and Psoriasismentioning

confidence: 91%

“…In the phase 2 study, tofacitinib had efficacies of 25.0% (2 mg twice daily), 40.8% (5 mg twice daily), and 66.7% (15 mg twice daily) compared to 2% for the placebo in terms of PASI75 response at week 12 of treatment [12]. Across the phase 3 studies, tofacitinib had efficacies of 39.5-54.3% (5 mg [13][14][15][16]. The highest PASI75 responses at both dosages were observed in an Asian population [16].…”

Section: Tofacitinib and Psoriasismentioning

confidence: 99%

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Systemic Treatment of Psoriasis with JAK Inhibitors: A Review

Kvist-Hansen

Hansen

Skov

2019

Dermatol Ther (Heidelb)

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Psoriasis is a prevalent chronic inflammatory disease. The inflammatory response is driven by T cells and mediated by multiple cytokines such as tumor necrosis factor and the interleukins IL-17 and IL-23. Moderate-to-severe psoriasis is treated systemically, using either biologics or conventional treatments with small-molecule drugs. The newer biologics are very effective and well tolerated, but not all patients respond to treatment with biologics, so there is a need for new treatment options for psoriasis. Janus kinase (JAK) inhibitors are a new drug class that may be of use in this respect. These inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. They block the intracellular signal pathway mediated by JAK and signal transducer and activator of transcription (STAT) proteins, thereby inhibiting gene transcription of proinflammatory cytokines. JAK inhibitors are currently being tested as potential treatments for psoriasis. They have shown clinical efficacy as measured by the Psoriasis Area and Severity Index 75 response in both phase 2 and 3 trials, and appear to be well tolerated overall. This review provides an overview of the mechanisms underlying the actions of JAK inhibitors in psoriasis, together with the results of clinical trials testing their efficacies when used to treat the disease.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Tofacitinib and Psoriasismentioning

confidence: 91%

Section: Tofacitinib and Psoriasismentioning

confidence: 99%

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Systemic Treatment of Psoriasis with JAK Inhibitors: A Review

Kvist-Hansen

Hansen

Skov

2019

Dermatol Ther (Heidelb)

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“…Tofacitinib, which is a first-generation JAK inhibitor, primarily targets JAK3, JAK2, and JAK1 [ 85 ]. In the phase 3 studies, the PASI75 response to tofacitinib at weeks 16–24 was 39.5–54.3% (5 mg twice daily) and 59.2–81.1% (10 mg twice daily), as compared to 5.6–12.5% for the placebo [ 86 , 87 , 88 , 89 ]. During the study, increased circulating total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and creatinine phosphokinase levels and decreased blood hemoglobin and lymphocyte counts were observed [ 85 ].…”

Section: Treatmentmentioning

confidence: 99%

New Treatment Addressing the Pathogenesis of Psoriasis

Tokuyama

Mabuchi

2020

IJMS

190

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Psoriasis is an immune cell-mediated inflammatory skin disease. The interleukin (IL)23/IL17 axis plays an important role in the development of psoriasis. The effectiveness of biologic treatments such as tumor necrosis factor (TNF)α inhibitors (infliximab, adalimumab, certolizumab pegol), IL23 inhibitors (ustekinumab, guselkumab, tildrakizumab, risankizumab), and IL17 inhibitors (secukinumab, ixekizumab, brodalumab) have verified these findings. Immune-related cells such as dendritic cells (DCs) and macrophages, in addition to Toll-like receptors and cytokines such as interferon (IFN)α, TNFα, IFNɤ, IL12, IL22, IL23, and IL17, are related to the pathogenesis of psoriasis. Here, we first review new insights regarding the pathogenesis of psoriasis, as it relates to DCs, Langerhans cells, macrophages, the signal transducer and activator of transcription 3 pathway, and aryl hydrocarbon receptor in cutaneous vascular endothelial cells. Based on these findings, we summarize currently available oral treatments and biologics. Furthermore, we describe a new treatment option including Janus kinase inhibitor, tyrosine kinase 2 inhibitor, modulator of sphingosine 1-phosphate receptor 1, and Rho-associated kinase 2 inhibitor.

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Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

Ingrassia,

Maqsood,

Gelfand

et al. 2024

JAMA Dermatol

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ImportanceJanus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.ObjectiveTo determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.Data SourcesPubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.Study SelectionThis review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.Data Extraction and SynthesisThis study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresPrimary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.ResultsThe analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).Conclusions and RelevanceIn this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

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The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: A Phase 3, randomized, double-blind, placebo-controlled study

Abstract: Tofacitinib demonstrated efficacy vs placebo at Week 16 in Asian patients with moderate to severe plaque psoriasis; efficacy was maintained through Week 52. No unexpected safety findings were observed. [NCT01815424].

Cited by 69 publications

References 30 publications

Systemic Treatment of Psoriasis with JAK Inhibitors: A Review

Systemic Treatment of Psoriasis with JAK Inhibitors: A Review

New Treatment Addressing the Pathogenesis of Psoriasis

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

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