Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study.

Background: Ustekinumab is a monoclonal antibody targeting interleukin (IL)-12 and IL-23 and is approved for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-12 and IL-23 have been implicated in systemic lupus erythematosus. We aimed to assess the efficacy and safety of ustekinumab for the treatment of systemic lupus erythematosus in patients with moderate-to-severe disease activity despite conventional treatment.

Development and validation of panoptic Meso scale discovery assay to quantify total systemic interleukin-6.

Aim: Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms ranging from a low molecular weight (MW 20-30 kDa) non-complexed form to high MW (200-450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to understand clinical responses to IL-6-targeted treatments. Existing assays measure only the low MW, non-complexed IL-6 form.

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab.

Objective: To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA).

Methods: GO-REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14.

Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate or methotrexate alone.

Objective: We assessed whether the addition of anti-tumor necrosis factor (TNF) agent to methotrexate (MTX) therapy might alter the response of patients with rheumatoid arthritis (RA) to pneumococcal vaccination.

Methods: Seventy patients with early RA (n = 20, 36, and 14 in the infliximab 3 mg/kg plus MTX, infliximab 6 mg/kg plus MTX, and placebo plus MTX groups, respectively) were included in an analysis of patients enrolled in an ASPIRE substudy. Patients received 0.

Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease.

Objectives: The long-term effect of infliximab on endoscopic and histologic disease activity and expression of inflammatory markers was assessed in Crohn's disease patients who received infliximab as episodic or scheduled maintenance therapy therapy over 54 weeks (ACCENT 1).

Methods: All patients received Infliximab 5 mg/kg at week 0 and at week 2 were then randomized as responders or nonresponders to placebo or infliximab (5 or 10mg/kg). Patients received placebo or infliximab 5 mg/kg at weeks 2 and 6 followed by placebo or infliximab (5 or 10mg/kg) every 8 weeks or episodically on loss of response.

Formation, distribution, and elimination of infliximab and anti-infliximab immune complexes in cynomolgus monkeys.

Infliximab (IFX) is a chimeric IgG1 monoclonal antibody specific for human tumor necrosis factor-alpha that is approved in the United States and Europe for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Approximately 10% of RA and CD patients receiving maintenance treatment with IFX will develop antibodies to IFX. The objective of this study was to develop a model to assess the in vivo formation, distribution, and elimination of immune complexes resulting from a low-level immune response in the presence of the excess concentration of a therapeutic antigen.

Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease.

Background & Aims: The effect of different treatment regimens on antibody responses to infliximab and their clinical significance was examined by using data from ACCENT I.

Methods: Patients with Crohn's disease (n = 573) received 5 mg/kg infliximab (week 0) and then were randomly assigned to blinded infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (group I), 5 mg/kg infliximab (group II), or 5 mg/kg infliximab at weeks 2 and 6, followed by 10 mg/kg thereafter (group III). At week 14 or later, patients losing response could cross over to episodic infliximab treatment increased by 5 mg/kg.

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris.

Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial.

Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6.

Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic transgenic mice.

Anti-tumor-necrosis-factor-alpha (TNF-alpha) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-alpha (hTNF-alpha) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-alpha antibody was assessed using various pathological indicators of disease progression.

The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To investigate the relationship between serum concentrations of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody, and clinical improvement from infliximab therapy for rheumatoid arthritis (RA).

Methods: Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay.