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Tofacitinib

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https://www.readbyqxmd.com/read/28407099/discontinuation-of-tofacitinib-after-achieving-low-disease-activity-in-patients-with-rheumatoid-arthritis-a-multicentre-observational-study
#1
Satoshi Kubo, Kunihiro Yamaoka, Koichi Amano, Shuji Nagano, Shigeto Tohma, Eiichi Suematsu, Hayato Nagasawa, Kanako Iwata, Yoshiya Tanaka
Objective.: To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). Methods.: RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52...
April 12, 2017: Rheumatology
https://www.readbyqxmd.com/read/28396102/efficacy-of-tofacitinib-for-the-treatment-of-nail-psoriasis-two-52-week-randomized-controlled-phase-3-studies-in-patients-with-moderate-to-severe-plaque-psoriasis
#2
Joseph F Merola, Boni Elewski, Svitlana Tatulych, Shuping Lan, Anna Tallman, Mandeep Kaur
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated. OBJECTIVE: We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks. METHODS: In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily...
April 7, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28389165/cytomegalovirus-retinitis-followed-by-immune-recovery-uveitis-in-an-elderly-patient-with-rheumatoid-arthritis-undergoing-administration-of-methotrexate-and-tofacitinib-combination-therapy
#3
Kunio Yanagisawa, Yoshiyuki Ogawa, Mayumi Hosogai, Daisuke Todokoro, Takeki Mitsui, Akihiko Yokohama, Shoji Kishi, Hiroshi Handa
Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection most commonly observed in patients infected with human immunodeficiency virus (HIV). We present a rare case of CMV retinitis that developed in a non-HIV patient with rheumatoid arthritis (RA). Over the preceding 5 months, a family doctor had been treating the 78-year-old male patient with a combination therapy of methotrexate (MTX) and tofacitinib (TOF). CMV retinitis occurred when the patient's CD4+ T cells were low (196 cells/μl), and preceded the onset of Pneumocystis pneumonia...
April 4, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28382662/successful-targeted-treatment-of-mast-cell-activation-syndrome-with-tofacitinib
#4
Lawrence B Afrin, Roger W Fox, Susan L Zito, Leo Choe, Sarah C Glover
Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile...
April 6, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28377787/tofacitinib-versus-biologic-treatments-in-moderate-to-severe-rheumatoid-arthritis-patients-who-have-had-an-inadequate-response-to-nonbiologic-dmards-systematic-literature-review-and-network-meta-analysis
#5
REVIEW
Evelien Bergrath, Robert A Gerber, David Gruben, Tatjana Lukic, Charles Makin, Gene Wallenstein
Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015...
2017: International Journal of Rheumatology
https://www.readbyqxmd.com/read/28371574/tofacitinib-suppresses-disease-activity-and-febrile-attacks-in-a-patient-with-coexisting-rheumatoid-arthritis-and-familial-mediterranean-fever
#6
Kevser Gök, Gizem Cengiz, Kemal Erol, Salih Ozgocmen
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA)...
January 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28369741/janus-kinase-inhibitors-prevent-migration-of-rheumatoid-arthritis-neutrophils-towards-interleukin-8-but-do-not-inhibit-priming-of-the-respiratory-burst-or-reactive-oxygen-species-production
#7
T S Mitchell, R J Moots, H L Wright
Neutrophils play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via the release of reactive oxygen species (ROS), proteases and cytokines. Orally active Janus kinase (JAK) inhibitors (JAKi), e.g. baricitinib and tofacitinib, have high clinical efficacy in RA but are linked with neutropenia and increased infections. Our aim was to determine the effect of JAK inhibition with baricitinib and tofacitinib on healthy control and RA neutrophil lifespan and function. RA (n = 7) and healthy control (n = 7) neutrophils were treated with baricitinib or tofacitinib for 30 min, prior to incubation in the absence or presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon (IFN)-γ...
April 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28356243/efficacy-of-glucocorticoids-conventional-and-targeted-synthetic-disease-modifying-antirheumatic-drugs-a-systematic-literature-review-informing-the-2016-update-of-the-eular-recommendations-for-the-management-of-rheumatoid-arthritis
#8
Katerina Chatzidionysiou, Sharzad Emamikia, Jackie Nam, Sofia Ramiro, Josef Smolen, Désirée van der Heijde, Maxime Dougados, Johannes Bijlsma, Gerd Burmester, Marieke Scholte, Ronald van Vollenhoven, Robert Landewé
OBJECTIVES: To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). METHODS: An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials. RESULTS: For GCs, four studies were included in the SLR...
March 29, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28355451/treatment-of-alopecia-areata-with-tofacitinib
#9
Omer Ibrahim, Cheryl B Bayart, Sara Hogan, Melissa Piliang, Wilma F Bergfeld
No abstract text is available yet for this article.
March 29, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28329404/tofacitinib-in-the-treatment-of-rheumatoid-arthritis-and-chronic-plaque-psoriasis
#10
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
#11
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
#12
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
#13
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...
April 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
#14
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
#15
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
#16
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
#17
REVIEW
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...
April 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
#18
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
#19
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
#20
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...
April 2017: Drugs
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