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https://www.readbyqxmd.com/read/29672874/review-article-novel-oral-targeted-therapies-in-inflammatory-bowel-disease
#1
REVIEW
J R White, F Phillips, T Monaghan, W Fateen, S Samuel, S Ghosh, G W Moran
BACKGROUND: There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases. AIMS: To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management...
April 19, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29658800/nail-involvement-in-patients-with-moderate-to-severe-alopecia-areata-treated-with-oral-tofacitinib
#2
Ji Su Lee, Chang-Hun Huh, Ohsang Kwon, Hyun-Sun Yoon, Soyun Cho, Hyun-Sun Park
BACKGROUND: A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA. OBJECTIVE: To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib. METHODS: This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months. RESULTS: Fifteen patients had nail involvement and demonstrated more severe hair loss than those without nail involvement (p = 0...
April 16, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29656373/evaluation-of-disease-activity-in-patients-with-rheumatoid-arthritis-treated-with-tofacitinib-by-rapid3-post-hoc-analyses-from-two-phase-3-trials
#3
Vibeke Strand, Eun Bong Lee, Yusuf Yazici, Ara Dikranian, Bethanie Wilkinson, Liza Takiya, Chuanbo Zang, Eustratios Bananis, Martin J Bergman
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We evaluated the relationship between disease activity, according to Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background MTX...
April 14, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29648682/elderly-onset-varicella-pneumonia-in-a-patient-with-rheumatoid-arthritis-taking-tofacitinib
#4
Nobuya Abe, Takashi Kudo, Satoshi Jodo
A 68-year-old woman with rheumatoid arthritis, who was treated with tofacitinib, a type of Janus kinase (JAK) inhibitor, was admitted for dyspnea and generalized purpuric vesicular rash, following 3 days of fever and malaise. She developed hypoxia from respiratory insufficiency. On physical examination, the systemic eruptions had an erythematous base and were present in various stages, from maculopapular to vesicular and pustular, with crusting (left). Chest radiograph demonstrated diffuse infiltrates with reticular and nodular lesions in the bilateral lung fields (right)...
April 12, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29622655/repurposing-tofacitinib-as-an-anti-myeloma-therapeutic-to-reverse-growth-promoting-effects-of-the-bone-marrow-microenvironment
#5
Christine Lam, Ian D Ferguson, Margarette C Mariano, Yu-Hsiu T Lin, Megan Murnane, Hui Liu, Geoffrey A Smith, Sandy W Wong, Jack Taunton, Jun O Liu, Constantine S Mitsiades, Byron C Hann, Blake T Aftab, Arun P Wiita
The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Here, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models...
April 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29620612/tofacitinib-halts-progression-of-graft-dysfunction-in-a-rat-model-of-mixed-cellular-and-humoral-rejection
#6
Jordi Rovira, María J Ramírez-Bajo, Elisenda Banon-Maneus, Marta Lazo-Rodríguez, Daniel Moya-Rull, Natalia Hierro-Garcia, Valeria Tubita, Gastón J Piñeiro, Ignacio Revuelta, Pedro Ventura-Aguiar, David Cucchiari, Federico Oppenheimer, Mercè Brunet, Josep M Campistol, Fritz Diekmann
BACKGROUND: The progression from acute to chronic antibody-mediated rejection in kidney transplant recipients is usually not prevented by current therapeutic options. Here, we investigated whether the use of tofacinitib, a Janus kinase 3 inhibitor, was capable of preventing the progression of allograft dysfunction in a Fisher-to-Lewis rat model of kidney transplantation. METHODS: Rats were treated from the third week after transplantation in order to allow the development of rejection...
April 3, 2018: Transplantation
https://www.readbyqxmd.com/read/29618084/the-rationale-for-janus-kinase-inhibitors-for-the-treatment-of-spondyloarthritis
#7
Douglas J Veale, Dennis McGonagle, Iain B McInnes, James G Krueger, Christopher T Ritchlin, Dirk Elewaut, Keith S Kanik, Thijs Hendrikx, Gabriel Berstein, Jennifer Hodge, Jean-Baptiste Telliez
The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations...
April 3, 2018: Rheumatology
https://www.readbyqxmd.com/read/29589185/contemporary-management-of-ulcerative-colitis
#8
REVIEW
Rohini Vanga, Millie D Long
PURPOSE OF REVIEW: We discuss the newest evidence-based data on management of ulcerative colitis (UC). We emphasize risk-stratification, optimizing medical therapies, and surgical outcomes of UC. RECENT FINDINGS: Recent medical advances include introduction of novel agents for UC. Vedolizumab, an anti-adhesion molecule, has demonstrated efficacy in moderate to severe UC. Tofacitinib, a small molecule, has also demonstrated efficacy. Data on optimization of infliximab show the superiority of combination therapy with azathioprine over monotherapy with infliximab or azathioprine alone...
March 27, 2018: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29587202/stattic-inhibits-rankl-mediated-osteoclastogenesis-by-suppressing-activation-of-stat3-and-nf-%C3%AE%C2%BAb-pathways
#9
Chang-Hong Li, Lin-Lin Xu, Lei-Lei Jian, Ruo-Han Yu, Jin-Xia Zhao, Lin Sun, Guo-Hong Du, Xiang-Yuan Liu
Tofacitinib, a small molecule JAK inhibitor, has been widely used to reduce inflammation and inhibit progression of bone destruction in rheumatoid arthritis. STAT3, a downstream signaling molecule of JAK, plays a key role in the activation of signaling in response to inflammatory cytokines. Thus, targeting STAT3 may be an inspiring strategy for treating osteoclast-related diseases such as rheumatoid arthritis. In this study, we first investigated the effects of Stattic, a STAT3 inhibitor, on receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis...
March 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29566769/effectiveness-and-safety-of-tofacitinib-in-rheumatoid-arthritis-a-cohort-study
#10
Marina Amaral de Ávila Machado, Cristiano Soares de Moura, Steve Ferreira Guerra, Jeffrey R Curtis, Michal Abrahamowicz, Sasha Bernatsky
BACKGROUND: Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. METHODS: We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics...
March 23, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29556726/new-treatment-options-for-inflammatory-bowel-diseases
#11
REVIEW
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29546668/tofacitinib-for-treating-rheumatoid-arthritis-after-the-failure-of-disease-modifying-anti-rheumatic-drugs-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#12
REVIEW
Lesley Uttley, Iñigo Bermejo, Shijie Ren, Marrissa Martyn-St James, Ruth Wong, David L Scott, Adam Young, Matt Stevenson
As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Pfizer) of tofacitinib (TOF; Xeljanz® ) to submit evidence of the drug's clinical and cost-effectiveness in the treatment of rheumatoid arthritis (RA) after the failure of conventional disease-modifying antirheumatic drugs (cDMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
March 15, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29546543/maldi-imaging-facilitates-new-topical-drug-development-process-by-determining-quantitative-skin-distribution-profiles
#13
David Bonnel, Raphaël Legouffe, André H Eriksson, Rasmus W Mortensen, Fabien Pamelard, Jonathan Stauber, Kim T Nielsen
Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration...
March 15, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29545454/a-systematic-review-and-metaanalysis-of-antirheumatic-drugs-and-vaccine-immunogenicity-in-rheumatoid-arthritis
#14
Sujith Subesinghe, Katie Bechman, Andrew I Rutherford, David Goldblatt, James B Galloway
OBJECTIVE: Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity. METHODS: We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcal polysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs...
March 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29518827/-stimulator-of-interferon-genes-associated-vasculopathy-with-onset-in-infancy-first-case-report-in-china
#15
Z X Yu, L Q Zhong, H M Song, C Y Wang, W Wang, J Li, M S Ma
Objective: To summarize the clinical characteristics and treatment efficacy of the first reported case of a Chinese boy with stimulator of interferon genes (STING) associated vasculopathy with onset in infancy (SAVI). Methods: Sanger sequencing of the gene TMEM173 was performed based on systemic evaluation and clinical analysis of a highly suspected SAVI child admitted to Peking Union Medical College Hospital. A literature search (search terms included 'STING''SAVI''autoinflammatory diseases' and 'interferonopathy') was conducted using Chinese literature database, EMBASE and PubMed to include recently published SAVI studies (searched from January 2010 to December 2017)...
March 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29518577/reversibility-of-peripheral-blood-leukocyte-phenotypic-and-functional-changes-after-exposure-to-and-withdrawal-from-tofacitinib-a-janus-kinase-inhibitor-in-healthy-volunteers
#16
Kent J Weinhold, Jack F Bukowski, Todd V Brennan, Robert J Noveck, Janet S Staats, Liwen Lin, Linda Stempora, Constance Hammond, Ann Wouters, Christopher F Mojcik, John Cheng, Mark Collinge, Michael I Jesson, Anasuya Hazra, Pinaki Biswas, Shuping Lan, James D Clark, Jennifer A Hodge
This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%...
March 5, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29512229/the-anti-inflammatory-effect-of-topical-tofacitinib-on-immediate-and-late-phase-cutaneous-allergic-reactions-in-dogs-a-placebo-controlled-pilot-study
#17
Amanda Blubaugh, Daniel Rissi, Deborah Elder, Tara Denley, Sitka Eguiluz-Hernandez, Frane Banovic
BACKGROUND: Topical Janus kinase (JAK) inhibition is a promising therapeutic target for several inflammatory skin diseases of humans. OBJECTIVES: To evaluate the anti-inflammatory effect of tofacitinib, a JAK 1/3 inhibitor, on immediate and late-phase skin reactions in dogs. ANIMALS: Five healthy laboratory beagle dogs. METHODS: Topical tofacitinib (total daily dosage: 0.5 mg/cm2 ) or its gel vehicle were applied on either the left or right lateral thorax of each dog for eight days...
March 6, 2018: Veterinary Dermatology
https://www.readbyqxmd.com/read/29500799/thromboembolism-with-janus-kinase-jak-inhibitors-for-rheumatoid-arthritis-how-real-is-the-risk
#18
Ian C Scott, Samantha L Hider, David L Scott
Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs)...
March 2, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#19
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29488102/therapeutics-for-adult-nail-psoriasis-and-nail-lichen-planus-a-guide-for-clinicians
#20
REVIEW
Danielle R McClanahan, Joseph C English
Nail psoriasis (NP) and nail lichen planus (NLP) can be limiting, stigmatizing and difficult to treat. Dermatologists commonly treat psoriasis and lichen planus but when associated onychodystrophy is present or is an isolated finding, some develop apprehension. The goal of this review is to develop therapeutic ladders to be used as a guide for the management of NP and NLP in everyday clinical practice. Evidence-based therapies for NP are robust and range from topical treatments to conventional systemic therapies (i...
February 27, 2018: American Journal of Clinical Dermatology
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