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Tofacitinib

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https://www.readbyqxmd.com/read/29045212/tofacitinib-or-adalimumab-versus-placebo-for-psoriatic-arthritis
#1
Philip Mease, Stephen Hall, Oliver FitzGerald, Désirée van der Heijde, Joseph F Merola, Francisco Avila-Zapata, Dorota Cieślak, Daniela Graham, Cunshan Wang, Sujatha Menon, Thijs Hendrikx, Keith S Kanik
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). METHODS: In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53)...
October 19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29045207/tofacitinib-for-psoriatic-arthritis-in-patients-with-an-inadequate-response-to-tnf-inhibitors
#2
Dafna Gladman, William Rigby, Valderilio F Azevedo, Frank Behrens, Ricardo Blanco, Andrzej Kaszuba, Elizabeth Kudlacz, Cunshan Wang, Sujatha Menon, Thijs Hendrikx, Keith S Kanik
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients)...
October 19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29043892/tofacitinib-in-the-treatment-of-active-rheumatoid-arthritis-in-adults
#3
Roy Fleischmann
Tofacitinib, a pan Janus kinase inhibitor, has been investigated as monotherapy in patients naive to methotrexate and in methotrexate incomplete responders and in combination with disease-modifying antirheumatic drugs in antirheumatic drug incomplete responders and TNF inhibitor failures in the Phase II and III programs. The clinical trial program demonstrated efficacy and a reasonable safety profile in these disease populations that has led to the approval of tofacitinib 5 mg twice daily orally in many countries...
October 18, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29040714/nice-issues-positive-recommendation-for-xeljanz%C3%A2-%C3%A2-tofacitinib-citrate-as-a-new-treatment-option-for-adults-with-severe-rheumatoid-arthritis
#4
(no author information available yet)
No abstract text is available yet for this article.
October 12, 2017: Rheumatology
https://www.readbyqxmd.com/read/29039054/treatment-persistence-and-healthcare-costs-among-patients-with-rheumatoid-arthritis-changing-biologics-in-the-usa
#5
Benjamin Chastek, Chieh-I Chen, Clare Proudfoot, Shraddha Shinde, Andreas Kuznik, Wenhui Wei
INTRODUCTION: After a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers. METHODS: This study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year...
October 16, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29034491/oral-tofacitinib-a-promising-treatment-in-atopic-dermatitis-alopecia-areata-and-vitiligo
#6
M Vu, C Heyes, S J Robertson, G A Varigos, G Ross
No abstract text is available yet for this article.
October 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29030660/tofacitinib-improves-atherosclerosis-despite-up-regulating-serum-cholesterol-in-patients-with-active-rheumatoid-arthritis-a-cohort-study
#7
Kensuke Kume, Kanzo Amano, Susumu Yamada, Toshikatsu Kanazawa, Hiroyuki Ohta, Kazuhiko Hatta, Kuniki Amano, Noriko Kuwaba
Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active RA (28-joint disease activity score-erythrocyte sedimentation rate > 3.2) despite methotrexate (MTX) treatment 12 mg/week were included in this open-label prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day). Japanese guideline does not allow high dose of MTX...
October 14, 2017: Rheumatology International
https://www.readbyqxmd.com/read/29029911/oral-tofacitinib-monotherapy-in-korean-patients-with-refractory-moderate-to-severe-alopecia-areata-a-case-series
#8
Hyun-Sun Park, Min-Woo Kim, Ji Su Lee, Hyun-Sun Yoon, Chang-Hun Huh, Ohsang Kwon, Soyun Cho
No abstract text is available yet for this article.
November 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29028981/tofacitinib-in-patients-with-ulcerative-colitis-health-related-quality-of-life-in-phase%C3%A2-3-randomized-controlled-induction-and-maintenance-studies
#9
Julian Panés, Séverine Vermeire, James O Lindsay, Bruce E Sands, Chinyu Su, Gary Friedman, Haiying Zhang, Aaron Yarlas, Martha Bayliss, Stephen Maher, Joseph C Cappelleri, Andrew G Bushmakin, David T Rubin
Background and Aims: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for UC. We evaluated healthrelated quality of life [HRQoL] in tofacitinib UC Phase 3 studies. Methods: Patients ≥18 years old in OCTAVE Induction 1 [N=598] and 2 [N=541] with moderately to severely active UC were randomized [1:4] to placebo or tofacitinib 10mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re-randomized [1:1:1] clinical responders [N=593] from induction studies to placebo, tofacitinib 5 or 10mg BID for 52 weeks...
September 27, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28994166/newer-treatments-of-psoriasis-regarding-il-23-inhibitors-phosphodiesterase-4-inhibitors-and-janus-kinase-inhibitors
#10
REVIEW
Dominika Wcisło-Dziadecka, Martyna Zbiciak-Nylec, Ligia Brzezińska-Wcisło, Katarzyna Bebenek, Agata Kaźmierczak
The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23)...
October 10, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28968875/effects-of-tofacitinib-in-early-arthritis-induced-bone-loss-in-an-adjuvant-induced-arthritis-rat-model
#11
Bruno Vidal, Rita Cascão, Mikko A J Finnilä, Inês P Lopes, Vânia G da Glória, Simo Saarakkala, Peter Zioupos, Helena Canhão, João Eurico Fonseca
Objectives: The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Methods: Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment...
August 10, 2017: Rheumatology
https://www.readbyqxmd.com/read/28967798/tofacitinib-in-psoriatic-arthritis
#12
Ting-Shun Wang, Tsen-Fang Tsai
Psoriatic arthritis is a heterogeneous disease that has been difficult to manage until the recent advent of biologics. However, there are still unmet medical needs for newer agents. Tofacitinib is a Janus family of kinases inhibitor approved for treating rheumatoid arthritis in many countries and psoriasis in Russia. We reviewed the evidences of tofacitinib in psoriatic arthritis treatment. The efficacy and safety profiles result from Phase III clinical trials (OPAL BROADEN and OPAL BEYOND) and one open-label extension study (OPAL BALANCE)...
October 2, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28947313/effectiveness-of-biologic-and-non-biologic-antirheumatic-drugs-on-anaemia-markers-in-153-788-patients-with-rheumatoid-arthritis-new-evidence-from-real-world-data
#13
Sanjoy Ketan Paul, Olga Montvida, Jennie H Best, Sara Gale, Attila Pethoe-Schramm, Khaled Sarsour
BACKGROUND: To evaluate the impact of treatment with disease-modifying antirheumatic drugs (DMARDs), including IL-6 receptor inhibitor tocilizumab (TCZ), on anaemia markers in patients with rheumatoid arthritis. METHODS: Using the Centricity Electronic Medical Records from USA, patients with rheumatoid arthritis diagnosed between January 2000 and April 2016, who initiated TCZ (n = 3732); tofacitinib (TOFA, n = 3126); other biologic DMARD (obDMARD, n = 55,964); or other non-biologic DMARD (onbDMARD, n = 91,236) were identified...
August 3, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28944566/design-and-synthesis-of-a-highly-selective-jak3-inhibitor-for-the-treatment-of-rheumatoid-arthritis
#14
Linhong He, Heying Pei, Tingxuan Lan, Minghai Tang, Chufeng Zhang, Lijuan Chen
Selective inhibition of Janus kinase 3 (JAK3) has been identified as an important strategy for the treatment of autoimmune disorders. Based on the unique cysteine 909 residue (Cys909) of JAK3 at the gatekeeper position, we have developed a new irreversible covalent inhibitor, III-4, which is highly potent and selective in targeting JAK3. Importantly, III-4 selectively inhibited JAK3 (IC50  = 57 ± 1.21 nM) over other JAKs (IC50  > 10 µM) and Cys909 kinome members (IC50  > 1 µM)...
September 25, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28941219/lymphoma-in-the-tofacitinib-rheumatoid-arthritis-clinical-development-program
#15
Xavier Mariette, Connie Chen, Pinaki Biswas, Kenneth Kwok, Mary G Boy
BACKGROUND: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program. METHODS: Lymphoma events (to March 2015) were identified from 19 tofacitinib studies (two Phase 1, nine Phase 2, six Phase 3, and two long-term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1-30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic DMARDs...
September 21, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28928840/a-cytokine-signal-inhibitor-for-rheumatoid-arthritis-enhances-cancer-metastasis-via-depletion-of-nk-cells-in-an-experimental-lung-metastasis-mouse-model-of-colon-cancer
#16
Hideki Shimaoka, Shinsuke Takeno, Kenji Maki, Takahide Sasaki, Suguru Hasegawa, Yuichi Yamashita
Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927890/reduction-of-inflammatory-and-cardiovascular-proteins-in-the-blood-of-psoriasis-patients-differential-responses-between-tofacitinib-and-etanercept-after-4-weeks-of-treatment
#17
Jaehwan Kim, Lewis Tomalin, Julie Lee, Lori J Fitz, Gabriel Berstein, Joel Correa-da Rosa, Sandra Garcet, Michelle A Lowes, Hernan Valdez, Robert Wolk, Mayte Suarez-Farinas, James G Krueger
Psoriasis patients have increased risk of myocardial infarction, and psoriasis is now recognized as an independent risk factor for coronary heart disease and cardiovascular mortality. To understand the effects of psoriasis medications on systemic inflammation associated with cardiovascular risks, we studied blood proteins related to inflammation and cardiovascular disease archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-severe psoriasis. 157 blood proteins were quantified by a proximity extension assay from 266 patients at baseline and week 4...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28919705/new-insight-into-the-pathogenesis-of-nail-psoriasis-and-overview-of-treatment-strategies
#18
REVIEW
Alessandra Ventura, Mauro Mazzeo, Roberta Gaziano, Marco Galluzzo, Luca Bianchi, Elena Campione
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient's physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28891341/small-molecule-therapy-for-managing-moderate-to-severe-psoriatic-arthritis
#19
Luisa Costa, Antonio Del Puente, Rosario Peluso, Marco Tasso, Paolo Caso, Maria Sole Chimenti, Vincenzo Sabbatino, Nicolò Girolimetto, Carolina Benigno, Nicoletta Bertolini, Aurora Del Puente, Roberto Perricone, Raffaele Scarpa, Francesco Caso
The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28884378/efficacy-of-topical-tofacitinib-in-promoting-hair-growth-in-non-scarring-alopecia-possible-mechanism-via-vegf-induction
#20
Jitlada Meephansan, J Thummakriengkrai, S Ponnikorn, W Yingmema, R Deenonpoe, P Suchonwanit
Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation...
September 7, 2017: Archives of Dermatological Research
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