Medicine and Health Sciences Commons^™

Methotrexate-Induced Pancytopenia: A Call For Mindful Medication Practices, Eunbee Cho, Jessica Marcela Daza, Jiye A. Park, Shreel Patel, Seokwon Choi, Daniel Farray

Research Symposium

Introduction: Methotrexate(MTX) is a widely used disease-modifying antirheumatic drug for various conditions including autoimmune diseases or malignancies. Pancytopenia as an adverse effect of methotrexate is rarely reported but sometimes fatal, and requires more attention. This case report shows a 76-year-old woman with a history of rheumatoid arthritis(RA) on MTX therapy, presenting with severe pancytopenia and oral lesions, and highlights the importance of safe medication practices especially in elderly patients with poor health literacy and compliance.

Case Presentation: A 76-year-old female with rheumatoid arthritis presented to the emergency department with a worsening oral lesion. She had been on an unspecified maintenance …

Cd39 Expression On Immune Cells Predicts Methotrexate Response In Rheumatoid Arthritis Patients, Bariş Boral, İbrahi̇m Tuncer, Fi̇li̇z Ki̇bar, Sali̇h Çeti̇ner, Suade Özlem Badak, Emrah Salman, Emrah Koç, Eren Erken, Akgün Yaman

Turkish Journal of Medical Sciences

Background/aim: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response. Materials and methods: This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American …

In Vitro Hepatotoxicity Evaluation Of Methotrexate-Loaded Niosome Formulation: Fabrication, Characterization And Cell Culture Studies, Ahmet Doğan Ergi̇n, Çağatay Oltulu, Nebi̇ye Peli̇n Türker, Gülen Meli̇ke Demi̇rbolat

Turkish Journal of Medical Sciences

Background/aim: Methotrexate (MTX) is a folic acid antagonist that is widely used to treat osteosarcoma, leukemia, breast cancer, and autoimmune and inflammatory diseases. The most important concerns with MTX are its poor solubility and high toxicity, particularly in liver cells. To enhance its solubility and to minimize its toxicity, we encapsulated MTX in niosomes and investigated its hepatotoxicity mechanisms using genetic biomarkers. Materials and methods: Niosomes were successfully prepared using a modified thin film method, and the prepared monodisperse smallsized formulation was subsequently characterized. In vitro cytotoxicity studies were performed both in hepatocarcinoma (HEP3G) and healthy liver (AML12) cell lines. …

Pengaruh Terapi Metotreksat Pada Pasien Artritis Reumatoid Terhadap Penurunan Fungsi Kognitif: Meta-Analisis Berdasarkan Telaah Sistematik, Fara Fauzia, Nurhayati Adnan Prihartono, Rudy Hidayat, Abirianti P. Araminta

Jurnal Penyakit Dalam Indonesia

Introduction. Rheumatoid arthritis (RA) is a systemic and chronic autoimmune disease involving the joints disorder as the main manifestations. Methotrexate (MTX) is currently still the drug of choice for RA treatment due to the good clinical response. However, there was a case reported by the American Geriatric Society in 2015 regarding the presence of reversible dementia after treatment with low-dose oral methotrexate. This study aimed to identify the effect of MTX treatment on cognitive disorder in RA patients.

Methods. The study protocol was registered with PROSPERO (CRD42023414937). A systematic literature search was conducted in Medline Embase database, Scopus, CENTRAL …

Promoting Healthier Treatment Outcomes In Obese Cancer Patients Taking High Dose Methotrexate, Carly Dell'ova

Walden Dissertations and Doctoral Studies

Cancer and obesity rates continue to rise, creating enormous public heath burdens to the individual and at the national and global levels, reducing quality of life, and increasing spending. Moreover, the relationships between cancer and obesity are not well understood. A commonly used chemotherapy for several types of cancer is high dose methotrexate (HDMTX). Along with chemotherapy, especially at high doses, comes toxicity to specific organs and the entire body. However, limited research has been conducted on obese cancer patients as they are often excluded from clinical studies. Practitioners need to better understand how to dose these patients to provide …

Anatomical Changes And Ovarian Reserve Assessment Following Methotrexate Therapy In Tubal Ectopic Pregnancy, Ayman S. Dawood, Hesham M. Borg, Mona K. Omar

Journal of Medicine in Scientific Research

Background Methotrexate (MTX) therapy for ectopic pregnancy (EP) is widely used as an alternative for surgical treatment. Its effects on ovarian reserve or pelvic anatomy are not well established. Aims The aim was to evaluate anatomical changes and ovarian reserve in cases of tubal EP treated by MTX therapy. Materials and methods A prospective cohort study was conducted at Tanta University. All patients with EP were enrolled. Eligible patients were treated by MTX. Ovarian reserve was assessed by anti-Mullerian hormone (AMH) level and antral follicle count (AFC) 3 months after treatment. Anatomical changes were assessed by laparoscopy 6 months after …

Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke

Senior Honors Theses

The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …

Sex-Based Differences In Functional Brain Activity During Working Memory In Survivors Of Pediatric Acute Lymphoblastic Leukemia, Kellen Gandy, Matthew A Scoggins, Nicholas Phillips, Ellen Van Der Plas, Slim Fellah, Lisa M Jacola, Ching-Hon Pui, Melissa M Hudson, Wilburn E Reddick, Ranganatha Sitaram, Kevin R Krull

2020-Current year OA Pubs

BACKGROUND: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone.

METHODS: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Is The Treatment Of Inflammatory Arthritis Different In Sickle Cell Disease?, Gezmi̇ş Ki̇myon, Gül İlhan

Turkish Journal of Medical Sciences

Background/aim: Musculoskeletal findings are common in sickle cell patients and may be confused with inflammatory arthritis. In addition, complications such as frequent infections may create difficulties while choosing drugs such as steroids, methotrexate, or antiTNFs. Our aim is to reveal whether the treatment is different in sickle cell patients with rheumatic diseases such as rheumatoid arthritis. Materials and methods: Patients followed by Rheumatology and Hematology divisions of Hatay Mustafa Kemal University Hospital were retrospectively screened. Excluding patients with musculoskeletal findings associated with sickle cell disease (SCD), patients with chronic or acute inflammatory arthritis were enrolled into study. Demographic data, disease …

Steroid-Refractory Lichenoid Eruption Associated With Pembrolizumab In A Patient With Non-Small Cell Lung Cancer, Leon Kou, Sanjay Agarwal, Alyssa Miceli, Logan Kolb, Karthik Krishnamurthy, Shawn Schmieder

HCA Healthcare Journal of Medicine

Programmed cell death receptor 1 (PD-1) inhibitors are promising and effective treatments for various cancers. Cutaneous adverse events, such as lichenoid drug eruptions, are well-known common side effects associated with PD-1 inhibitors. Lichenoid drug eruptions associated with PD-1 inhibitors show rapid improvement with high potency topical steroids and do not require cessation of the offending drug. We present the case of an 84-year-old female with progressive pembrolizumab therapy-associated lichenoid eruption that was resistant to several treatments and ultimately required discontinuation of pembrolizumab and treatment with methotrexate to resolve. This report includes histological findings of the pembrolizumab-associated lichenoid eruption.

Perceptions And Challenges Experienced By African Physicians When Prescribing Methotrexate For Rheumatic Disease: An Exploratory Study, Carol A Hitchon, Girsh M Mody, Candace H Feldman, Yan Lau, Steven Shi, Michele Meltzer, Rosie Scuccimarri, Michael E Weinblatt, Ines Colmegna

Department of Medicine Faculty Papers

Objective: Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations.

Methods: African physicians who self-identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L-HDI versus MH-HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI.

Results: Physicians (23 rheumatologists; …

Potential Role Of Methotrexate Polyglutamates In Therapeutic Drug Monitoring For Pediatric Inflammatory Bowel Disease., Ryan Morrow, Ryan Funk, Mara Becker, Ashley K. Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)-promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1-6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman's correlation (ρ) …

Application Of An Evidence-Based, Out-Patient Treatment Strategy For Covid-19: Multidisciplinary Medical Practice Principles To Prevent Severe Disease☆, Elliot M. Frohman, Nicole R. Villemarette-Pittman, Adriana Rodriguez, Robert Glanzman, Sarah Rugheimer, Oleg Komogortsev, Scott S. Zamvil, Roberto A. Cruz, Thomas C. Varkey, Ashley N. Frohman

School of Medicine Publications and Presentations

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of …

Targeting The Phgdh-Mtor Metabolic Axis In Osteosarcoma, Richa Rathore

Arts & Sciences Electronic Theses and Dissertations

Altering cellular energy metabolism has been highlighted as one of the emerging hallmarks of cancer. The reprogramming of bioenergetic pathways towards enhanced glycolysis, rather than the mitochondrial oxidative phosphorylation indicative of normal cells, results in increased biomass production and is associated with the activation of various oncogenes. The increased or decreased expression of key metabolic enzymes has been identified as a potential family of biomarkers that could serve as the targets for novel metabolic-based therapies in cancer.

The serine, glycine, and one-carbon (SGOC) metabolism pathway consists of a series of enzymes and metabolites that drive protein and lipid production, enhanced …

Part I. Sars-Cov-2 Triggered 'Panic' Attack In Severe Covid-19, Elliot M. Frohman, Nicole R. Villemarette-Pittman, Esther Melamed, Roberto A. Cruz, Reid Longmuir, Thomas C. Varkey, Lawrence Steinman, Scott S. Zamvil, Teresa C. Frohman

School of Medicine Publications and Presentations

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues.

In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized …

Part Ii. High-Dose Methotrexate With Leucovorin Rescue For Severe Covid-19: An Immune Stabilization Strategy For Sars-Cov-2 Induced 'Panic' Attack, Elliot M. Frohman, Nicole R. Villemarette-Pittman, Roberto A. Cruz, Reid Longmuir, Vernon Rowe, Elizabeth S. Rowe, Thomas C. Varkey, Lawrence Steinman, Scott S. Zamvil, Teresa C. Frohman

School of Medicine Publications and Presentations

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely …

Successful Treatment Of A Cervical Ectopic Pregnancy With Single-Dose Methotrexate Therapy, Hannah Dearworth, Jesse Cottrell

Marshall Journal of Medicine

Ectopic pregnancies implanted in the cervix account for less than 1 percent of all extra-uterine pregnancies. Due to the limited incidence of cervical ectopic pregnancies, there are no established guidelines for medical versus surgical management. We report a case of a cervical ectopic pregnancy with a fetal heartbeat successfully treated with single dose methotrexate therapy.

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …

Treatment Of Idiopathic Granulomatous Mastitis And Factors Related With Disease Recurrence, Emre Tekgöz, Seda Çolak, Muhammet Çinar, Sedat Yilmaz

Turkish Journal of Medical Sciences

Background/aim: Idiopathic granulomatous mastitis is a rare, benign inflammatory disease of breast. There is no general agreement on the appropriate treatment choice.The aim of the study was to investigate the immunosuppressive administer for idiopathic granulomatous mastitis and risk factors related with disease recurrence.Materials and methods: The data of 53 patients with idiopathic granulomatous mastitis were evaluated for this cross-sectional retrospective study. Demographic features and clinical characteristics and course of the patients were obtained from file records. Results: The mean age of the patients was 37.2 ± 6.6 years. Fifty-one of 53 patients received immunosuppressive treatment with or without surgery. Forty-seven …

Protective Effects Of Apocynin On Damaged Testes Of Rats Exposed To Methotrexate, Kübra Kavram Sarihan, Melda Yardimoğlu Yilmaz, Fatma Ceyla Eraldemi̇r, Yusufhan Yazir, Esra Acar

Turkish Journal of Medical Sciences

Background/aim: Methotrexate (MTX), widely used as a drug in cancer, has many adverse effects on tissues. Apocynin (APO) is a NADPH oxidase inhibitor and is known with many antioxidant properties. In this study, we aimed to evaluate the adverse effects of MTX on testicular tissue and the protective effects of APO at two different doses (20 mg/kg and 50 mg/kg) on MTX-induced testicular damage.Materials and methods: Fifty adult male Wistar albino rats (8 weeks old and weighing 200-250 g) were divided into five groups of 10 rats each: 1. saline control, 2. dimethyl sulfoxide (DMSO) control, 3. MTX, 4. APO-20 …

Physician Practices For Withdrawal Of Medications In Inactive Systemic Juvenile Arthritis, Childhood Arthritis And Rheumatology Research Alliance (Carra) Survey., Susan Shenoi, Kabita Nanda, Grant S. Schulert, John F. Bohnsack, Ashley M. Cooper, Bridget Edghill, Miriah C. Gillispie-Taylor, Baruch Goldberg, Olha Halyabar, Thomas G. Mason, Tova Ronis, Rayfel Schneider, Richard K. Vehe, Karen Onel, Childhood Arthritis And Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis Workgroup

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We describe a Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey of North American pediatric rheumatologists that assesses physician attitudes on withdrawal of medications in systemic juvenile idiopathic arthritis (SJIA).

METHODS: A REDCap anonymous electronic survey was distributed to 100 random CARRA JIA workgroup physician-voting members. The survey had three broad sections including: A) demographic information; B) physicians' opinions on clinical inactive disease (CID) in SJIA and C) existing practices for withdrawing medications in SJIA.

RESULTS: The survey had an 86% response rate. 88 and 93% of participants agreed with the current criteria for CID and clinical remission on …

Developing Comparative Effectiveness Studies For A Rare, Understudied Pediatric Disease: Lessons Learned From The Carra Juvenile Localized Scleroderma Consensus Treatment Plan Pilot Study., Suzanne C. Li, Robert C. Fuhlbrigge, Ronald M. Laxer, Elena Pope, Maria Ibarra, Katie Stewart, Thomas Mason, Mara L. Becker, Sandy Hong, Fatma Dedeoglu, Kathryn S. Torok, C Egla Rabinovich, Polly J. Ferguson, Marilynn Punaro, Brian M. Feldman, Tracy Andrews, Gloria C. Higgins, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases.

METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize …

A Deadly Prescription: Combination Of Methotrexate And Trimethoprim-Sulfamethoxazole., Mohsin Hamid, Bilal Lashari, Irfan Ahsan, Ida Micaily, Usman Sarwar, Joseph Crocetti

Abington Jefferson Health Papers

Methotrexate (MTX) is a chemotherapeutic synthetic(s) phase cell cycle inhibitor, and its role has evolved as an immunological agent in autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc. Trimethoprim-sulfamethoxazole (TS) is one of the most widely prescribed antibiotics commonly used for urinary tract infections, exacerbations of chronic bronchitis, traveler's diarrhea, and pneumocystis pneumonia. Both MTX and TS can have significantly overlapping side effects involving dermatologic, renal, and hematological systems, and the combination of these can be deadly. Our case is about the combination of MTX and TS that leads to mucocutaneous ulceration, leukopenia, and renal insufficiency. The …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

Assessing The Comparative Effect Of Tocilizumab On Risk Of Cardiovascular Disease Among Rheumatoid Arthritis Patients Using Claims Data: A Direct Comparison Among Biologic Disease-Modifying Antirheumatic Drugs, Fenglong Xie

All ETDs from UAB

ASSESSING THE COMPARATIVE EFFECT OF TOCILIZUMAB ON RISK OF CARDIOVASCULAR DISEASE AMONG RHEUMATOID ARTHRITIS PATIENTS USING CLAIMS DATA: A DIRECT COMPARISON AMONG BIOLOGIC DISEASEMODIFYING ANTIRHEUMATIC DRUGS FENGLONG XIE PhD-EPID ABSTRACT Tocilizumab is a humanized monoclonal anti-body against the interleukin-6 receptor and is effective in the treatment of rheumatoid arthritis (RA) [1]. Multiple studies have observed unfavorable changes in the lipid profile of tocilizumab-treated RA patients. Few studies have compared the cardiovascular disease (CVD) risk associated with tocilizumab to other biologic disease-modifying antirheumatic drugs (bDMARDS). Due to limitations in existing studies, the real-world association of tocilizumab with CVD risk remains uncertain. …

Nanomedicine For Immunosuppressive Therapy: Achievements In Pre-Clinical Research, Hanan Al-Lawati, Hamidreza Montazeri Aliabadi, Behzad Sharif Makhmalzadeh, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues.

Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as …

Ixekizumab Efficacy And Safety With And Without Concomitant Conventional Disease-Modifying Antirheumatic Drugs (Cdmards) In Biologic Dmard (Bdmard)-Naive Patients With Active Psoriatic Arthritis (Psa): Results From Spirit-P1, Laura Coates, M Kishimoto, Alice Gottlieb, C Shuler, C Lin, C Lee, P Mease

NYMC Faculty Publications

Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239). Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naive use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety …

Secukinumab Sustains Improvement In Signs And Symptoms Of Psoriatic Arthritis: 2 Year Results From The Phase 3 Future 2 Study., Iain B Mcinnes, Philip Mease, Christopher T Ritchlin, Proton Rahman, Alice B Gottlieb, Bruce Kirkham, Radhika Kajekar, Eumorphia-Maria Delicha, Luminita Pricop, Shephard Mpofu

Articles, Abstracts, and Reports

Objectives: To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA.

Methods: Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, …

Tocilizumab Combination Therapy Or Monotherapy Or Methotrexate Monotherapy In Methotrexate-Naive Patients With Early Rheumatoid Arthritis: 2-Year Clinical And Radiographic Results From The Randomised, Placebo-Controlled Function Trial, Gerd R. Burmester, William F. Rigby, Ronald F. Van Vollenhoven, Jonathan Kay, Andrea Rubbert-Roth, Ricardo Blanco, Alysha Kadva, Sophie Dimonaco

Jonathan Kay

OBJECTIVE: Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104. METHODS: Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) < /=3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory. RESULTS: Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission ( < 2.6) …