Low immunogenicity of tocilizumab in patients with rheumatoid arthritis.

Objective: Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods: Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients).

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy.

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy.

Targeting ABCB1 (MDR1) in multi-drug resistant osteosarcoma cells using the CRISPR-Cas9 system to reverse drug resistance.

Background: Multi-drug resistance (MDR) remains a significant obstacle to successful chemotherapy treatment for osteosarcoma patients. One of the central causes of MDR is the overexpression of the membrane bound drug transporter protein P-glycoprotein (P-gp), which is the protein product of the MDR gene ABCB1. Though several methods have been reported to reverse MDR in vitro and in vivo when combined with anticancer drugs, they have yet to be proven useful in the clinical setting.

Clinical outcomes for patients after surgery and radiation therapy for mesenchymal chondrosarcomas.

Introduction: We report the outcome of 23 patients with mesenchymal chondrosarcomas treated with surgery and radiation therapy +/- chemotherapy. The intent of the project was to review the impact of patient and treatment variables on treatment outcome, in particular with regard to extent of surgery and radiation dose.

Patients And Methods: Twenty-three patients with mesenchymal chondrosarcomas were treated with surgery and radiation therapy (min.

Preoperative radiation therapy combined with radical surgical resection is associated with a lower rate of local recurrence when treating unifocal, primary retroperitoneal liposarcoma.

Background And Objectives: Local recurrence (LR) is the primary cause of death in patients with retroperitoneal liposarcoma (RP-LPS). The purpose of this study was to evaluate if the addition of preoperative radiation therapy (XRT) to radical resection for RP-LPS at a single institution was associated with improved LR.

Methods: This retrospective analysis included patients with unifocal, primary RP-LPS who underwent complete R0/R1 resection at a single institution between 1991 and 2013.

Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials.

Objectives: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events.

Consensus Decision Models for Biologics in Rheumatoid and Psoriatic Arthritis: Recommendations of a Multidisciplinary Working Party.

Introduction: Biologic therapies are efficacious but costly. A number of health economic models have been developed to determine the most cost-effective way of using them in the treatment pathway. These models have produced conflicting results, driven by differences in assumptions, model structure, and data, which undermine the credibility of funding decisions based on modeling studies.

Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor.

Background: Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed.

Methods: The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ≥50%.

PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma.

Purpose Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding the generation of toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with doxorubicin plus placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients and Methods Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m intravenously day 1 plus palifosfamide 150 mg/m/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles.

Differences in sex distribution, anatomic location and MR imaging appearance of pediatric compared to adult chordomas.

Background: Chordomas are rare malignancies that primarily affect adults, but also rarely affect pediatric patients. We compared the imaging appearance, demographic and anatomic distributions of adult and pediatric chordomas in a large cohort.

Methods: We performed a retrospective review of medical records of 220 subjects with histologically confirmed chordomas of the axial skeleton and pre-treatment magnetic resonance imaging studies.

TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma.

In tumours that harbour wild-type p53, p53 protein function is frequently disabled by the mouse double minute 2 protein (MDM2, or HDM2 in humans). Multiple HDM2 antagonists are currently in clinical development. Preclinical data indicate that TP53 mutations are a possible mechanism of acquired resistance to HDM2 inhibition; however, this resistance mechanism has not been reported in patients.

Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis.

Current EULAR guidelines state that biologic DMARD (bDMARD) therapy should be administered in combination with MTX or other conventional synthetic (cs) DMARD in RA. Nonetheless, a third of patients for whom a bDMARD agent is prescribed take it in the absence of concurrent csDMARD therapy. While the reasons underlying the low uptake of bDMARD-csDMARD combination therapy in clinical practice have not been well delineated, they may include poor adherence, contraindication to csDMARD therapy and adverse effects, as well as csDMARD withdrawal following remission.

Anti cytokine therapy in chronic inflammatory arthritis.

This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17.

Defining criteria for rheumatoid arthritis patient-derived disease activity score that correspond to Disease Activity Score 28 and Clinical Disease Activity Index based disease states and response criteria.

Objective: Two versions of a patient-based DAS (PDAS) 1 and 2 (with and without ESR) have been developed and validated in RA. The objective of this study was to define PDAS1- and PDAS2-based criteria for remission, low, moderate and high disease activity and responses to treatment.

Method: Using receiver operating characteristic curves, the optimal thresholds for PDAS1 and PDAS2 that correspond to validated assessor-based DAS (DAS28) and Clinical Disease Activity Index (CDAI) disease statuses were determined.

The Width of the Surgical Margin Does Not Influence Outcomes in Extremity and Truncal Soft Tissue Sarcoma Treated With Radiotherapy.

Background And Objectives: It is unclear whether the quantitative width of the surgical margin influences outcomes in patients with extremity and truncal soft tissue sarcoma (STS) treated with radiotherapy (RT).

Methods: We performed a retrospective review of 382 patients with localized extremity or truncal STS who underwent limb-sparing surgery and RT from 1983 to 2010, and we analyzed the significance of resection margin status and quantitative margin width on outcomes.

Results: Surgical margins were positive in 68 (18%) patients and negative in 314 (82%) patients.

EULAR revised recommendations for the management of fibromyalgia.

Objective: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'.

Methods: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia.

Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy.

Background: This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST.

Patients And Methods: The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib.

Current treatments to counter sleep dysfunction as a pathogenic stimulus of fibromyalgia.

Fibromyalgia is characterized by chronic widespread pain, fatigue and nonrestorative sleep. Polysomnography showed reduced short-wave sleep and abnormal alpha rhythms during nonrapid eye movement sleep in patients with fibromyalgia. However, sleep dysfunction might be pathogenic in fibromyalgia since myalgia and fatigue could be induced in healthy individuals by disrupting sleep.

Biologic interventions for fatigue in rheumatoid arthritis.

Background: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage.

Objectives: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis.

Frequency and Risk Factors for Additional Lesions in the Axial Spine in Subjects With Chordoma: Indications for Screening.

Study Design: Retrospective cohort study.

Objective: We aim to evaluate the frequency and clinical significance of additional lesions in the axial spine in subjects with chordoma and to assess the need for screening.

Summary Of Background Data: Chordomas are rare tumors that may be multicentric or metastasize and affect several bones in the axial spine.

Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set.

Objective: To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set.

Methods: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded.

Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel.

Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells.

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial.

Background: Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis.

Methods: This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK.