Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years.

Objective: To characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.

Methods: Data were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets.

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial.

Objectives: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.

Methods: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.

Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis.

Progressive lung fibrosis is a major cause of mortality in systemic sclerosis (SSc) patients, but the underlying mechanisms remain unclear. We demonstrate that immune complexes (ICs) activate human monocytes to promote lung fibroblast migration partly via osteopontin (OPN) secretion, which is amplified by autocrine monocyte colony stimulating factor (MCSF) and interleukin-6 (IL-6) activity. Bulk and single-cell RNA sequencing demonstrate that elevated OPN expression in SSc lung tissue is enriched in macrophages, partially overlapping with CCL18 expression.

Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis.

Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan.

Characterizing Disease Manifestations and Treatment Patterns Among Adults with Systemic Sclerosis: A Retrospective Analysis of a US Healthcare Claims Population.

Introduction: Real-world use of immunomodulating therapy (IMT) in patients with systemic sclerosis (SSc) was investigated for the first time in a descriptive, retrospective cohort analysis of claims made in a healthcare insurance database to characterize treatment patterns and their alignment with SSc disease manifestations.

Methods: Treatment patterns and disease manifestations, symptoms, complications, and comorbidities were assessed in patients with SSc enrolled in a US healthcare claims database who received treatment between January 2006 and December 2013 and for whom data were available 6 months before and 12 months after SSc diagnosis.

Results: Among 7812 eligible patients, 6852 received treatments of interest for SSc and 2404 (30.

Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE Registry.

Objective: To evaluate the long-term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥ 1 antitumor necrosis factor therapies in the United States (SUNSTONE Registry).

Methods: In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard-of-care follow-up visits at least every 6 months. The primary outcome was the incidence of protocol-defined significant infections.

Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis.

Objective: At present, there are no clinical or laboratory measures that accurately forecast the progression of skin fibrosis and organ involvement in patients with systemic sclerosis (SSc). The goal of this study was to identify skin biomarkers that could be prognostic for the progression of skin fibrosis in patients with early diffuse cutaneous SSc (dcSSc).

Methods: We analyzed clinical data and gene expression in skin biopsy samples from 38 placebo-treated patients, part of the Roche Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (FASSCINATE) phase II study of tocilizumab in SSc.

Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.

Objectives: Skin fibrosis mediated by activated dermal fibroblasts is a hallmark of systemic sclerosis (SSc), especially in the subset of patients with diffuse disease. Transforming growth factor-beta (TGFβ) and interleukin-6 (IL-6) are key candidate mediators in SSc. Our aim was to elucidate the specific effect of IL-6 pathway blockade on the biology of SSc fibroblasts in vivo by using samples from a unique clinical experiment-the faSScinate study-in which patients with SSc were treated for 24 weeks with tocilizumab (TCZ), an IL-6 receptor-α inhibitor.

Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

Objectives: Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo.

Methods: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks.

Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate).

Objectives: Assess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.

Methods: Patients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.

Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial.

Background: Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis.

Methods: We did this double-blind, placebo-controlled study at 35 hospitals in Canada, France, Germany, the UK, and the USA.

Using registries to identify adverse events in rheumatic diseases.

The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators.

Integrated safety in tocilizumab clinical trials.

Introduction: The efficacy and safety of tocilizumab in patients with rheumatoid arthritis have been evaluated in a comprehensive phase 3 program. Patients from these randomized trials could receive tocilizumab treatment in open-label extension trials. Here, the long-term safety profile of tocilizumab, using pooled data from all of these trials, is reported.

Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate.

Objective: To assess the effect of rituximab plus methotrexate (MTX) compared with MTX alone on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) in patients with active early rheumatoid arthritis (RA) previously untreated with MTX.

Methods: Patients with active early RA were randomized to groups receiving placebo, rituximab 500 mg, or rituximab 1,000 mg. Rituximab was given by intravenous infusion on days 1 and 15.

Subset analysis of patients experiencing clinical events of a potentially immunogenic nature in the pivotal clinical trials of tocilizumab for rheumatoid arthritis: Evaluation of an antidrug antibody ELISA using clinical adverse event-driven immunogenicity testing.

Background: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody directed against the interleukin-6 receptor. In Europe, TCZ is approved for use in combination with methotrexate in the treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who have failed to respond to or were unable to tolerate previous therapy with one or more disease-modifying antirheumatic drugs or tumor necrosis factor (TNF) antagonists; in the United States, it is approved for the treatment of adult patients with moderate to severe active RA who have failed to respond to one or more TNF antagonists. As part of the Phase III clinical development program, the immunogenicity of TCZ was evaluated using a bridging ELISA; however, this assay is considered limited in detecting low-affinity or immunoglobulin G4 subisotype antidrug antibodies (ADAs).

A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis.

Introduction: Preclinical work has suggested that IL-1 plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week).

Methods: Patients were randomized equally to receive placebo or 50, 125, or 250 mg AMG 108 subcutaneously every 4 weeks for 6 months.

Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

Background: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated.

Objective: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis.

Methods: A total of 912 patients received 50 mg subcutaneous etanercept once weekly (OW) for the first 12 weeks of this extension study.

Patient-reported outcomes in pediatric patients with psoriasis undergoing etanercept treatment: 12-week results from a phase III randomized controlled trial.

Background: Psoriasis adversely affects health-related quality of life (HRQoL) in adults; however, little information exists about its impact on children and adolescents.

Objective: The effect of etanercept therapy on HRQoL compared with placebo was evaluated in children and adolescents with moderate to severe plaque psoriasis.

Methods: HRQoL data were collected from patients 4 to 17 years of age in a randomized, double-blind, placebo-controlled, North American, phase III study of etanercept.

Etanercept treatment for children and adolescents with plaque psoriasis.

Background: Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.

Methods: In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.

Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis.

Objective: To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly.

Design, Setting, And Patients: A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005.