Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid Arthritis

Cohen, Stanley; Curtis, Jeffrey R.; DeMasi, Ryan; Chen, Yan; Fan, Huiying; Süner, Arif; Fleischmann, Roy

doi:10.1007/s40744-018-0097-3

Cited by 70 publications

(69 citation statements)

References 15 publications

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“…In patients with AD, a phase IIa study showed improvement of the Eczema Area and Severity Index (EASI) scores after 4 weeks of topical tofacitinib treatment . In rheumatoid arthritis, tofacitinib has been approved since 2012 and has shown minimal adverse events and good tolerance . Although the action of small molecule inhibitors, such as JAK1/3 inhibitors, is rather well understood on leucocytes, little is known about direct effects of kinase inhibitors on human keratinocyte function and skin barrier formation.…”

Section: Introductionmentioning

confidence: 99%

JAK1/3 inhibition preserves epidermal morphology in full‐thickness 3D skin models of atopic dermatitis and psoriasis

Clarysse

Pfaff

Marquardt

et al. 2019

Acad Dermatol Venereol

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Background Janus kinase (JAK) inhibition may be a promising new treatment modality for inflammatory (skin) diseases. However, little is known about direct effects of kinase inhibitors on keratinocyte differentiation and function as well as skin barrier formation. Objective Our aim was to address the direct impact of kinase inhibition of the JAK1/3 pathways by tofacitinib on keratinocyte immune function and barrier formation in atopic dermatitis (AD) and psoriasis. Methods 3D skin equivalents of both diseases were developed and concurrently pretreated with tofacitinib. To induce AD, 3D skin equivalents were stimulated with recombinant human IL‐4 and IL‐13. Psoriasis‐like conditions were induced by incubation with IL‐17A, IL‐22 and tumour necrosis factor α (TNFα). The activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT6 was assessed by Western blot analysis. Microarray analysis and quantitative real‐time PCR were used for gene expression analysis. Results Tofacitinib pretreatment preserved epidermal morphology and reduced STAT3 and STAT6 phosphorylation of AD‐like and STAT3 phosphorylation of psoriasis‐like culture conditions in 3D skin models compared to sham‐controls. Filaggrin expression was fully maintained in the AD‐like models, but only partially in psoriasis‐like conditions after pretreatment with tofacitinib. In addition, tofacitinib upregulated DSC1, FLG and KRT1. Using gene expression analysis, downregulation of POSTN and IL24 was observed in AD‐like conditions, whereas downregulation of IL20 and IL1B was observed in psoriasis‐like conditions. Conclusion JAK1/3 inhibition counteracted cytokine‐induced AD‐ and psoriasis‐like epidermal morphology and enhanced keratinocyte differentiation in 3D skin models. This effect was more pronounced in the AD‐like models compared to the psoriasis‐like 3D skin models.

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Section: Introductionmentioning

confidence: 99%

JAK1/3 inhibition preserves epidermal morphology in full‐thickness 3D skin models of atopic dermatitis and psoriasis

Clarysse

Pfaff

Marquardt

et al. 2019

Acad Dermatol Venereol

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“…5 Further, recent post-marketing surveillance experience has revealed two cases of histoplasmosis in patients on tofacitinib occurring in endemic regions. 6 To our knowledge, this is the first case of phaeohyphomycosis with tofacitinib and adds to the growing literature of mycoses related to the use of Janus-kinase inhibitors.…”

Section: Tofacitinib: Raising Awareness Of Mycosesmentioning

confidence: 61%

“…In an integrated safety analysis of 6194 patients on tofacitinib, out of 61 cases of opportunistic infection, there were 12 cases of oesophageal candidiasis, 5 cases of pneumocystosis and 5 cases of cryptococcal infection . Further, recent post‐marketing surveillance experience has revealed two cases of histoplasmosis in patients on tofacitinib occurring in endemic regions . To our knowledge, this is the first case of phaeohyphomycosis with tofacitinib and adds to the growing literature of mycoses related to the use of Janus‐kinase inhibitors.…”

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confidence: 99%

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Tofacitinib: raising awareness of mycoses

Dyer

Morwood

Choong

2019

Internal Medicine Journal

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“…It is characterized by the presence of autoantibodies and erosive synovitis that mainly involves small joints (1). Tofacitinib is the first oral Janus Kinase (JAK) inhibitor approved in 2012 for the treatment of patients with active, moderate to severe RA that does not respond to other therapies (2). Objectives: The objective was to describe demographic and clinical results of a cohort of Colombian patients with RA treated with tofacitinib.…”

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confidence: 99%

Ab0441 therapy With Tofacitinib in a Colombian Population With Rheumatoid Arthritis: Results of the Daily Clinical Practice

Zuleta

Díaz

Herrera³

et al. 2019

Abstracts Accepted for Publication

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Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the quality of life and reduces life expectancy. It is characterized by the presence of autoantibodies and erosive synovitis that mainly involves small joints (1). Tofacitinib is the first oral Janus Kinase (JAK) inhibitor approved in 2012 for the treatment of patients with active, moderate to severe RA that does not respond to other therapies (2).Objectives:The objective was to describe demographic and clinical results of a cohort of Colombian patients with RA treated with tofacitinib.Methods:Descriptive observational study of a historical cohort of RA patients in a specialized center for the management of inflammatory arthropathies, from April 2014 to February 2018. The following variables are described: age, sex, time evolution of the disease, type of AR, comorbidities, disease activity (DAS-28), schedule and treatment time. For the descriptive analysis, categorical variables are presented as absolute and relative frequencies; while continuous variables are presented as mean and standard deviation (SD) or median and interquartile range (IQR) according to distribution. The outcome of DAS 28 ≤ 3.2 was estimated by incidence rate, defined as the number of patients who presented the outcome divided by the summation of total exposure time of the patients.Results:Of 59 patients included, 88.1% (52) were women, with a median age of 58.8 years (IQR 49-68 years), 74.6% were seropositive, the median time from diagnosis was 18.2 years (IQR 12- 28.3 years). High blood pressure was the most common comorbidity (40.7%) and 7% had tuberculosis history. The median number of bDMARD prior to tofacitinib was 2 (IQR 1-3). Sixty six percent patients (39) were on monotherapy while 34% (20) were on combination with leflunomide (19) and methotrexate (1). The median time of treatment was 1.2 years (IQR 0.6-2 years). At the beginning, 84.7% patients (50) were in moderate or high disease activity and 15,3% (9) in remission or low activity; at the end of follow-up, 47.5% (28) were in remission or low activity and 52.5% (31) in moderate or high activity (p = 0.000). The mean DAS28 at the beginning of tofacitinib was 4.6 ± 1.55 and at the end of the follow-up was 3.5 ± 1.49, with a difference of means of 1.10 (IC95% 0.62-1.57), (p 0.00). During the follow-up period, the rate of development of remission or low activity was 11.92 (95% CI 8.35-16.51) cases per 100 people-month observed (p 0.00). Only 2 patients developed therapeutic failure.Conclusion:Tofacitinib shows a good profile of effectivity in patients with failure to prior bDMARD. Almost 50% patient reaches low disease activity or remission during follow up and low number of therapeutic failure was found.References[1] Picchianti-Diamanti A, et al. Front Microbiol. 2018;8(2696):1-9[2] Cohen S, et al. Rheumatol Ther. 2018;5(1):283-291Disclosure of Interests:Wilmer Gerardo Rojas Zuleta Speakers bureau: Bristol-Myers Squibb, Novartis, Jannsen, Pfizer, Oscar Jair Felipe Díaz Speakers bureau: Bristol-Myers Sq...

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Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid Arthritis

Abstract: Pfizer Inc.

Cited by 70 publications

References 15 publications

JAK1/3 inhibition preserves epidermal morphology in full‐thickness 3D skin models of atopic dermatitis and psoriasis

JAK1/3 inhibition preserves epidermal morphology in full‐thickness 3D skin models of atopic dermatitis and psoriasis

Tofacitinib: raising awareness of mycoses

Ab0441 therapy With Tofacitinib in a Colombian Population With Rheumatoid Arthritis: Results of the Daily Clinical Practice

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