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https://www.readbyqxmd.com/read/28329404/tofacitinib-in-the-treatment-of-rheumatoid-arthritis-and-chronic-plaque-psoriasis
#1
A K Gupta, M Cernea, C W Lynde
Tofacitinib is an oral immunosuppressant approved for the treatment of rheumatoid arthritis (RA) and is currently undergoing investigation (Phase III trials) for treating chronic plaque psoriasis. Tofacitinib inhibits Janus kinases (JAKs), which are essential for the signaling of multiple inflammatory pathways and have been implicated in the pathogenesis of RA and psoriasis. The efficacy and safety of tofacitinib in the treatment of RA and psoriasis have been demonstrated in Phase III trials. Across all studies, the efficacy of tofacitinib in alleviating symptoms of RA and psoriasis were superior to placebo...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28325392/experience-with-oral-tofacitinib-in-8-adolescent-patients-with-alopecia-universalis
#2
Leslie Castelo-Soccio
No abstract text is available yet for this article.
April 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28317328/evaluating-dosage-optimality-for-tofacitinib-an-oral-janus-kinase-inhibitor-in-plaque-psoriasis-and-the-influence-of-body-weight
#3
M M Hutmacher, K Papp, S Krishnaswami, K Ito, H Tan, R Wolk, H Valdez, C Mebus, S T Rottinghaus, P Gupta
Tofacitinib is an oral Janus kinase inhibitor. An integrated analysis was conducted to evaluate dosage optimality for tofacitinib in patients with moderate-to-severe plaque psoriasis and the impact of body weight on optimality in this patient population. Data were pooled from one phase IIb trial (2, 5, and 15 mg twice daily (b.i.d.)) and four phase III trials (5 and 10 mg b.i.d.). A longitudinal exposure-response model for Psoriasis Area and Severity Index (PASI) improvement (percent change from baseline) was established...
March 20, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28295194/anti-leukaemic-activity-of-the-tyk2-selective-inhibitor-ndi-031301-in-t-cell-acute-lymphoblastic-leukaemia
#4
Koshi Akahane, Zhaodong Li, Julia Etchin, Alla Berezovskaya, Evisa Gjini, Craig E Masse, Wenyan Miao, Jennifer Rocnik, Rosana Kapeller, Jeremy R Greenwood, Hong Tiv, Takaomi Sanda, David M Weinstock, A Thomas Look
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28284845/risks-of-malignancies-related-to-tofacitinib-and-biological-drugs-in-rheumatoid-arthritis-systematic-review-meta-analysis-and-network-meta-analysis
#5
José Ramón Maneiro, Alejandro Souto, Juan J Gomez-Reino
OBJECTIVE: To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs). METHODS: Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks...
February 16, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28284718/novel-jak3-activating-mutations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#6
Sung H Sim, Soyeon Kim, Tae M Kim, Yoon K Jeon, Soo J Nam, Yong-Oon Ahn, Bhumsuk Keam, Hyun H Park, Dong-Wan Kim, Chul W Kim, Dae S Heo
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3(A573V), two JAK3(H583Y), and one JAK3(G589D) mutation...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28282491/biologics-or-tofacitinib-for-people-with-rheumatoid-arthritis-unsuccessfully-treated-with-biologics-a-systematic-review-and-network-meta-analysis
#7
REVIEW
Jasvinder A Singh, Alomgir Hossain, Elizabeth Tanjong Ghogomu, Amy S Mudano, Lara J Maxwell, Rachelle Buchbinder, Maria Angeles Lopez-Olivo, Maria E Suarez-Almazor, Peter Tugwell, George A Wells
BACKGROUND: Biologic disease-modifying anti-rheumatic drugs (DMARDs: referred to as biologics) are effective in treating rheumatoid arthritis (RA), however there are few head-to-head comparison studies. Our systematic review, standard meta-analysis and network meta-analysis (NMA) updates the 2009 Cochrane overview, 'Biologics for rheumatoid arthritis (RA)' and adds new data. This review is focused on biologic or tofacitinib therapy in people with RA who had previously been treated unsuccessfully with biologics...
March 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28277884/investigational-drugs-for-treatment-of-juvenile-idiopathic-arthritis
#8
Angela Mauro, Donato Rigante, Rolando Cimaz
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The improvement of knowledge about the pathogenetic mechanisms of JIA and advances in the understanding of pathways linking inflammation and autoimmunity and functions of multiple transcription factors have translated into new drug development for a tailored treatment directed to specific subpopulations of JIA patients. Areas covered: This review provides a digest of new investigational drugs which are currently or have been recently tested for treatment of JIA, and highlights some early phase clinical trials on rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab...
March 12, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28270190/social-media-for-arthritis-related-comparative-effectiveness-and-safety-research-and-the-impact-of-direct-to-consumer-advertising
#9
Jeffrey R Curtis, Lang Chen, Phillip Higginbotham, W Benjamin Nowell, Ronit Gal-Levy, James Willig, Monika Safford, Joseph Coe, Kaitlin O'Hara, Roee Sa'adon
BACKGROUND: Social media may complement traditional data sources to answer comparative effectiveness/safety questions after medication licensure. METHODS: The Treato platform was used to analyze all publicly available social media data including Facebook, blogs, and discussion boards for posts mentioning inflammatory arthritis (e.g. rheumatoid, psoriatic). Safety events were self-reported by patients and mapped to medical ontologies, resolving synonyms. Disease and symptom-related treatment indications were manually redacted...
March 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28264816/eular-recommendations-for-the-management-of-rheumatoid-arthritis-with-synthetic-and-biological-disease-modifying-antirheumatic-drugs-2016-update
#10
Josef S Smolen, Robert Landewé, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, Sofia Ramiro, Marieke Voshaar, Ronald van Vollenhoven, Daniel Aletaha, Martin Aringer, Maarten Boers, Chris D Buckley, Frank Buttgereit, Vivian Bykerk, Mario Cardiel, Bernard Combe, Maurizio Cutolo, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Cem Gabay, Juan Gomez-Reino, Laure Gossec, Jacques-Eric Gottenberg, Johanna M W Hazes, Tom Huizinga, Meghna Jani, Dmitry Karateev, Marios Kouloumas, Tore Kvien, Zhanguo Li, Xavier Mariette, Iain McInnes, Eduardo Mysler, Peter Nash, Karel Pavelka, Gyula Poór, Christophe Richez, Piet van Riel, Andrea Rubbert-Roth, Kenneth Saag, Jose da Silva, Tanja Stamm, Tsutomu Takeuchi, René Westhovens, Maarten de Wit, Désirée van der Heijde
Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib)...
March 6, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28255960/jak-stat-signaling-as-a-target-for-inflammatory-and-autoimmune-diseases-current-and-future-prospects
#11
REVIEW
Shubhasree Banerjee, Ann Biehl, Massimo Gadina, Sarfaraz Hasni, Daniella M Schwartz
The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases...
March 3, 2017: Drugs
https://www.readbyqxmd.com/read/28250461/the-emerging-safety-profile-of-jak-inhibitors-in-rheumatic-disease
#12
REVIEW
Kevin L Winthrop
Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent...
April 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28245350/cardiovascular-safety-of-tocilizumab-versus-tumor-necrosis-factor-inhibitors-in-patients-with-rheumatoid-arthritis-a-multi-database-cohort-study
#13
Seoyoung C Kim, Daniel H Solomon, James R Rogers, Sara Gale, Micki Klearman, Khaled Sarsour, Sebastian Schneeweiss
OBJECTIVE: While tocilizumab (TCZ) is known to increase LDL cholesterol, it is unclear whether TCZ increases cardiovascular (CV) risks in patients with rheumatoid arthritis (RA). METHODS: To examine comparative CV safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome was a composite CV endpoint of hospitalization for myocardial infarction (MI) or stroke...
February 28, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28240592/analysis-of-non-melanoma-skin-cancer-across-the-tofacitinib-rheumatoid-arthritis-clinical-programme
#14
Jeffrey R Curtis, Eun Bong Lee, George Martin, Xavier Mariette, Ketti K Terry, Yan Chen, Jamie Geier, John Andrews, Mandeep Kaur, Haiyun Fan, Chudy I Nduaka
OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the incidence of non-melanoma skin cancer (NMSC) across the tofacitinib RA development programme. METHODS: NMSC events (through August 2013) were identified in patients receiving tofacitinib in two Phase (P)1, eight P2, six P3 and two long-term extension (LTE) studies. In P123 studies, tofacitinib was administered at various doses (1-30 mg twice daily [BID], 20 mg once daily), as monotherapy or with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate...
February 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28213386/erratum-efficacy-and-safety-of-tofacitinib-following-inadequate-response-to-conventional-synthetic-or-biologic-diseasemodifying-antirheumatic-drugs
#15
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28210825/recovery-of-nail-dystrophy-potential-new-therapeutic-indication-of-tofacitinib
#16
REVIEW
Jose A Jaller, Juan J Jaller, Antonio M Jaller, Juan J Jaller-Char, Sineida Berbert Ferreira, Rachel Ferreira, Morton Scheinberg
Nail dystrophy is a heterogeneous skin condition and in some subtypes, is associated with autoimmune diseases in particular psoriasis and psoriatic arthritis. In this report, we show that tofacitinib, a novel therapy for rheumatoid arthritis, appears to be beneficial in patients with nail disease refractory to other conventional modes of therapy.
February 16, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28209624/tofacitinib-for-induction-and-maintenance-therapy-of-crohn-s-disease-results-of-two-phase-iib-randomised-placebo-controlled-trials
#17
Julian Panés, William J Sandborn, Stefan Schreiber, Bruce E Sands, Séverine Vermeire, Geert D'Haens, Remo Panaccione, Peter D R Higgins, Jean-Frederic Colombel, Brian G Feagan, Gary Chan, Michele Moscariello, Wenjin Wang, Wojciech Niezychowski, Amy Marren, Paul Healey, Eric Maller
OBJECTIVE: Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). DESIGN: We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks...
February 16, 2017: Gut
https://www.readbyqxmd.com/read/28201942/correction-to-early-clinical-response-to-tofacitinib-treatment-as-a-predictor-of-subsequent-efficacy-results-from-two-phase-3-studies-of-patients-with-moderate-to-severe-plaque-psoriasis
#18
(no author information available yet)
No abstract text is available yet for this article.
February 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28197884/therapies-of-early-advanced-and-late-onset-forms-of-axial-spondyloarthritis-and-the-need-for-treat-to-target-strategies
#19
REVIEW
Nurullah Akkoc, Gercek Can, Salvatore D'Angelo, Angela Padula, Ignazio Olivieri
PURPOSE OF REVIEW: This study aims to provide an update on current status of pharmacological therapies in early and advanced stages of axial spondyloarthritis (axSpA), as well as its late onset forms, and to discuss the need for treat to target strategies in this entity. RECENT FINDINGS: Efficacy of TNF inhibitors has been assessed in randomized controlled trials in axSpA, which included patients who had non-radiographic axSpA according to the ASAS classification criteria...
February 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28193636/evaluation-of-jak3-biology-in-autoimmune-disease-using-a-highly-selective-irreversible-jak3-inhibitor
#20
Fiona Elwood, David Witter, Jennifer Piesvaux, Brian Kraybill, Nathan Bays, Carla Alpert, Peter Goldenblatt, Yujie Qu, Irena Ivanovska, Hyun-Hee Lee, Chi-Sung Chiu, Hao Tang, Mark E Scott, Sujal Deshmukh, Mark Zielstorff, Alan Byford, Kalyan Chakravarty, Lauren Dorosh, Alexy Rivkin, Joel Klappenbach, Bo-Sheng Pan, Ilona Kariv, Christopher Dinsmore, Deborah Slipetz, Peter Dandliker
Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012)...
February 13, 2017: Journal of Pharmacology and Experimental Therapeutics
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