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https://www.readbyqxmd.com/read/28087506/a-randomised-phase-ii-study-evaluating-the-efficacy-and-safety-of-subcutaneously-administered-ustekinumab-and-guselkumab-in-patients-with-active-rheumatoid-arthritis-despite-treatment-with-methotrexate
#1
Josef S Smolen, Sandeep K Agarwal, Elena Ilivanova, Xie Lillian Xu, Ye Miao, Yanli Zhuang, Ivo Nnane, Waldemar Radziszewski, Andrew Greenspan, Anna Beutler, Daniel Baker
OBJECTIVE: Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy. METHODS: Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week)...
January 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28085749/sinusoidal-obstruction-syndrome-during-maintenance-therapy-for-acute-lymphoblastic-leukemia-with-6-mercaptopurine-and-methotrexate-a-pediatric-case-report
#2
Kevin O McNerney, Juan C Vasquez, Michael W Kent, Joseph M McNamara
We report a case of a child with pre-B cell acute lymphoblastic leukemia undergoing maintenance chemotherapy with 6-mercaptopurine and methotrexate (MTX) who developed sinusoidal obstruction syndrome after being treated with ciprofloxacin for BK viremia. This case represents a rare complication of maintenance therapy with MTX and 6-mercaptopurine, and suggests a drug interaction between ciprofloxacin and MTX.
January 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28085747/survival-outcome-of-filipino-children-with-acute-lymphoblastic-leukemia-treated-with-modified-berlin-frankfurt-muenster-hong-kong-acute-lymphoblastic-leukemia-bfm95-hkall97-protocol-in-a-tertiary-general-hospital-from-january-2005-to-december-2009-a-retrospective
#3
Amanda Christina C Dujua, Flerida G Hernandez
This retrospective cohort study is primarily aimed to evaluate the outcome of children ages 0 to 18 years old, with acute lymphoblastic leukemia and treated with a modified Berlin-Frankfurt-Muenster/Hong Kong Acute Lymphoblastic Leukemia (BFM95-HKALL97) protocol at University of Santo Tomas Hospital from January 2005 to December 2009. Seventy-eight patients were included. Majority were between 1 and 10 years old (87.2%), male (61.5%), with normal nutritional status, and classified as upper socioeconomic class (65...
January 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28084866/population-based-experience-on-primary-central-nervous-system-lymphoma-2000-2012-the-incidence-is-increasing
#4
Gunilla Enblad, Gustaf Martinsson, Eva Baecklund, Göran Hesselager, Christer Sundström, Rosie-Marie Amini, Hans Hagberg
BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden. PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95)...
January 13, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28084646/treatments-for-chronic-inflammatory-demyelinating-polyradiculoneuropathy-cidp-an-overview-of-systematic-reviews
#5
REVIEW
Anne Louise Oaklander, Michael Pt Lunn, Richard Ac Hughes, Ivo N van Schaik, Chris Frost, Colin H Chalk
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective...
January 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28084171/what-can-clinicians-learn-from-therapeutic-studies-about-the-treatment-of-acute-oral-methotrexate-poisoning
#6
Betty S Chan, Andrew H Dawson, Nicholas A Buckley
CONTEXT: Methotrexate (MTX) is an anti-folate drug that has been utilized in both malignant and chronic inflammatory conditions. Doctors are often concerned with a potential adverse outcome when managing patients with acute oral MTX poisoning given its potential for serious adverse reactions at therapeutic doses. However, there is surprisingly little data from acute poisoning cases and more data from the therapeutic use of high-dose MTX. OBJECTIVES: To review pharmacokinetic and pharmacological properties of MTX and systematically review series of acute MTX poisonings and therapeutic studies on high-dose MTX that provide pharmacokinetic or clinical data...
February 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28084041/salvage-therapy-for-children-with-relapsed-or-refractory-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#7
Yuichi Kodama, Atsushi Manabe, Hirohide Kawasaki, Itaru Kato, Keisuke Kato, Atsushi Sato, Kimikazu Matsumoto, Motohiro Kato, Hidefumi Hiramatsu, Hideki Sano, Takashi Kaneko, Megumi Oda, Akiko M Saito, Souichi Adachi, Keizo Horibe, Shuki Mizutani, Eiichi Ishii, Hiroyuki Shimada
BACKGROUND: In the tyrosine kinase inhibitor (TKI) era, outcomes after salvage therapy for relapsed or refractory Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remain unclear. PROCEDURE: The clinical courses of 19 patients with relapse (n = 13) or induction failure (n = 6) in the Japanese Pediatric Leukemia/Lymphoma Study Group Ph+ ALL04 study were retrospectively reviewed. RESULTS: Fifteen male and four female patients had a median age of 8 (range 4-15) years at relapse or induction failure...
January 13, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28083796/approaches-to-mitigate-the-unwanted-immunogenicity-of-therapeutic-proteins-during-drug-development
#8
Laura I Salazar-Fontana, Dharmesh D Desai, Tarik A Khan, Renuka C Pillutla, Sandra Prior, Radha Ramakrishnan, Jennifer Schneider, Alexandra Joseph
All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses...
January 12, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28082032/recommendations-for-the-use-of-parenteral-methotrexate-in-rheumatology
#9
Jesús Tornero Molina, Jaime Calvo Alen, Javier Ballina, María Ángeles Belmonte, Francisco J Blanco, Miguel Ángel Caracuel, Jordi Carbonell, Héctor Corominas, Eugenio Chamizo, Cristina Hidalgo, José Román Ivorra, José Luis Marenco, José Vicente Moreno Muelas, Santiago Muñoz-Fernández, Joan M Nolla, Trinidad Pérez, Raimon Sanmarti, Pilar Trenor, Claudia Urrego, Javier Vidal, José Rosas Gomez de Salazar
OBJECTIVE: To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. METHODS: A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library)...
January 9, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28081972/methotrexate-reduces-vaccine-specific-immunoglobulin-levels-but-not-numbers-of-circulating-antibody-producing-b-cells-in-rheumatoid-arthritis-after-vaccination-with-a-conjugate-pneumococcal-vaccine
#10
Meliha C Kapetanovic, Johanna Nagel, Inger Nordström, Tore Saxne, Pierre Geborek, Anna Rudin
BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccination. The mechanisms by which MTX exerts these effects in RA are unknown. We aimed to evaluate whether MTX reduces vaccine-specific serum Ig levels and their functionality in RA patients following vaccination with pneumococcal conjugate vaccine, and if numbers of antigen-specific circulating plasmablasts are affected...
January 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28079767/primary-gastric-choriocarcinoma-presenting-as-a-pregnancy-of-unknown-location
#11
Alyssa Larish, Amanika Kumar, Sarah Kerr, Carrie Langstraat
BACKGROUND: Pregnancy of unknown location presents a diagnostic challenge, in rare occasions leading to the diagnosis of malignancy. We describe a case of β-hCG-secreting nongestational primary gastric choriocarcinoma presenting as a pregnancy of unknown location. CASE: A 37-year-old woman, gravida 4 para 3013, presented with several days of vaginal bleeding and rising β-hCG level without ultrasound localization of pregnancy. The diagnosis of pregnancy of unknown location was made and methotrexate administered at a β-hCG level of 7,779 milli-international units/mL...
January 9, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28079512/long-term-treatment-response-in-rheumatoid-arthritis-patients-starting-adalimumab-or-etanercept-with-or-without-concomitant-methotrexate
#12
Merel J l'Ami, Eva L Kneepkens, Michael T Nurmohamed, Charlotte L M Krieckaert, Ingrid M Visman, Gert-Jan Wolbink
OBJECTIVES: To observe long-term clinical response and drug survival in a prospective two-year cohort study in rheumatoid arthritis (RA) patients starting adalimumab or etanercept treatment, with or without methotrexate (MTX), after failure of conventional DMARD therapy, including MTX. METHODS: Disease activity score of 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were collected of 873 consecutive RA patients, treated with adalimumab or etanercept, prospectively at baseline, 4, 16, 28, 40, 52, 78 and 104 weeks of biological therapy...
January 5, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28079500/efficacy-and-safety-of-tofacitinib-in-older-and-younger-patients-with-rheumatoid-arthritis
#13
Jeffrey R Curtis, Hendrik Schulze-Koops, Liza Takiya, Charles A Mebus, Ketti K Terry, Pinaki Biswas, Thomas V Jones
OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the efficacy and safety of tofacitinib 5 or 10 mg twice daily (BID), in patients with moderate to severe RA, aged ≥65 and <65 years. METHODS: Data were pooled from five Phase 3 trials and, separately, from two open-label long-term extension (LTE) studies (data cut-off April, 2012). Patients received tofacitinib, or placebo (Phase 3 only), with/without conventional synthetic DMARDs (mainly methotrexate)...
January 4, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28079339/survey-of-bullous-pemphigoid-in-an-italian-university-hospital-clinical-epidemiological-characteristics-and-follow-up
#14
Riccardo Balestri, Giulia Odorici, Annalisa Patrizi, Salvatore D Infusino, Michela Magnano, Federico Bardazzi
BACKGROUND: The clinical-epidemiological characteristics and course of bullous pemphigoid in the general population is not clear. Few studies have been performed to date, and only one in the Italian population more than ten years ago. We decided to evaluate the characteristics and outcome of patients admitted for a bullous pemphigoid at our Hospital in the last 4 years. METHODS: We retrospectively review the last 4 years' medical records of the Department of Dermatology of the University of Bologna, identifying all patients with histological and immunological data typical for bullous pemphigoid...
January 12, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28078727/second-cancer-incidence-in-primary-mediastinal-b-cell-lymphoma-treated-with-methotrexate-with-leucovorin-rescue-doxorubicin-cyclophosphamide-vincristine-prednisone-and-bleomycin-regimen-with-or-without-rituximab-and-mediastinal-radiotherapy-results-from-a-monoinstitutional
#15
Vitaliana De Sanctis, Marco Alfò, Alice Di Rocco, Michela Ansuinelli, Eleonora Russo, Mattia F Osti, Maurizio Valeriani, Giuseppe Minniti, Lavinia Grapulin, Daniela Musio, Stefano Bracci, Alessandra Spagnoli, Maria Luisa Moleti, Vincenzo Tombolini, Maurizio Martelli
Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3...
January 12, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28078672/determinants-for-drug-survival-of-methotrexate-in-patients-with-psoriasis-split-for-different-reasons-of-discontinuation-results-of-the-prospective-mtx-capture
#16
M Otero, J van den Reek, M Seyger, P Van Der Kerkhof, W Kievit, E de Jong
BACKGROUND: Methotrexate is a widely used treatment for psoriasis. It is important to gain insight into the reasons for discontinuation of methotrexate and determinants for drug survival. OBJECTIVES: To describe 5-year drug survival for methotrexate in patients with psoriasis split for different reasons of discontinuation, and to identify determinants for drug survival. METHODS: Data were extracted from a prospective psoriasis registry of patients treated with methotrexate (MTX-CAPTURE)...
January 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28077146/childhood-arthritis-and-rheumatology-research-alliance-consensus-clinical-treatment-plans-for-juvenile-dermatomyositis-with-skin-predominant-disease
#17
Susan Kim, Philip Kahn, Angela B Robinson, Bianca Lang, Andrew Shulman, Edward J Oberle, Kenneth Schikler, Megan Lea Curran, Lilliana Barillas-Arias, Charles H Spencer, Lisa G Rider, Adam M Huber
BACKGROUND: Juvenile dermatomyositis (JDM) is the most common form of the idiopathic inflammatory myopathies in children. A subset of children have the rash of JDM without significant weakness, and the optimal treatments for these children are unknown. The goal of this study was to describe the development of consensus clinical treatment plans (CTPs) for children with JDM who have active skin rashes, without significant muscle involvement, referred to as skin predominant JDM in this manuscript...
January 11, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28076839/chemotherapy-can-induce-weight-normalization-of-morbidly-obese-mice-despite-undiminished-ingestion-of-high-fat-diet
#18
Cheryl E Myers, Dominique B Hoelzinger, Tiffany N Truong, Lindsey A Chew, Arpita Myles, Leena Chaudhuri, Jan B Egan, Jun Liu, Sandra J Gendler, Peter A Cohen
Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076753/cd25-targeted-therapy-of-chemotherapy-resistant-leukemic-stem-cells-using-dr5-specific-trail-peptide
#19
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81...
January 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28076752/methotrexate-associated-primary-hepatic-malignant-lymphoma-following-hepatectomy-a-case-report
#20
Daisuke Takei, Tomoyuki Abe, Hironobu Amano, Naomichi Hirano, Tsuyoshi Kobayashi, Hideki Ohdan, Toshinori Kondo, Masahiro Nakahara, Toshio Noriyuki
INTRODUCTION: Recently, immunosuppressant-associated malignant lymphoma (ML) cases have been increasing along with the development of several effective immunosuppressant drugs for rheumatoid arthritis (RA). Among methotrexate (MTX)-associated lymphoproliferative disorders, primary hepatic lymphoma (PHL) in patients with RA following surgical resection has not been reported previously. PRESENTATION OF CASE: A 65-year-old woman who is a hepatitis B virus carrier with a history of RA was admitted...
December 21, 2016: International Journal of Surgery Case Reports
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