Ustekinumab pharmacokinetics

Ustekinumab is not recommended for the treatment of children with inflammatory bowel disease, but its off-label use is increasing despite a lack of pediatric pharmacokinetic data. The purpose of this review is to evaluate the therapeutic effects of Ustekinumab on children with inflammatory bowel disease and to recommend the best treatment regimen. Ustekinumab was the first biological treatment for a 10-year-old Syrian boy with steroid-refractory pancolitis who weighed 34 kg. A 260 mg/kg (~6 mg/kg) intravenous dose was followed by 90 mg of subcutaneous Ustekinumab at week 8 (induction)...

OBJECTIVE: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects. METHODS: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared...

BACKGROUND AND AIMS: The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics. METHODS: This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity...

OBJECTIVES: To describe the extrapolation approaches used to support intravenous (IV) golimumab for polyarticular juvenile idiopathic arthritis (pJIA) and juvenile psoriatic arthritis (jPsA) and subcutaneous (SC) ustekinumab for jPsA. METHODS: Pharmacokinetic, clinical response, and safety data from trials of IV golimumab and SC ustekinumab in polyarticular-course JIA (pc-JIA) (GO-VIVA) or pediatric psoriasis (PsO) (CADMUS and CADMUS Jr) and data from pivotal, phase 3 trials of these agents in adults with similar diseases were used to support extrapolation in pJIA and jPsA...

PURPOSE: Ustekinumab, a fully human immunoglobulin G1κ monoclonal antibody that antagonizes human interleukin-12/23p40, is an effective therapy for several immune-mediated inflammatory diseases, including Crohn's disease (CD). This work characterizes the population pharmacokinetic (PK) and exposure-response (E-R) relationships of ustekinumab in patients with CD using data from four Phase IIb/III clinical studies. METHODS: Serum ustekinumab concentration-time data from 1673 patients after IV and/or SC administration of ustekinumab were fitted simultaneously using nonlinear mixed effects modeling to develop a population PK model, which was subsequently used to evaluate simulation scenarios...

BACKGROUND: Despite the therapeutic efficacy of Ustekinumab (UST) in Crohn's disease (CD), loss of response (LOR) is observed over time. This study aims to evaluate the impact of the UST pharmacokinetics (PK) at induction on clinical and endoscopic outcomes, as well as to find predictive markers of UST response. METHODS: This retrospective study included 80 CD patients. Pharmacokinetics data (trough levels (TLs)) combined with clinical and biological parameters were fed into tailored logistic regression and tree-based ensemble techniques to predict clinical and endoscopic outcomes at one year of follow-up...

Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab...

BACKGROUND AND OBJECTIVES: Ustekinumab has been approved for the treatment of patients with plaque psoriasis (PSO), psoriatic arthritis (PSA), Crohn's disease (CD), and ulcerative colitis (UC). This study was performed to investigate whether the pharmacokinetics of ustekinumab differ across different disease populations. METHODS: An integrated population pharmacokinetic analysis was conducted to characterize ustekinumab pharmacokinetics across four disease indications (i...

The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis...

Exposure-response modeling is important to optimize dose and dosing regimens in clinical drug development. While primary clinical trial endpoints often have few categories and thus provide only limited information, sometimes there may be additional, more informative endpoints. Benefits of fully incorporating relevant information in longitudinal exposure-response modeling through joint modeling have recently been shown. This manuscript aims to further investigate the benefit of joint modeling of an ordered categorical primary endpoint with a related near-continuous endpoint, through the sharing of model parameters in the latent variable indirect response (IDR) modeling framework...

Therapeutic drug monitoring (TDM) is a useful strategy to optimize biologic medications for inflammatory bowel disease not responsive to standard dosing regimens. TDM is cost effective for anti-tumor necrosis factor agents in the setting of loss of response (reactive TDM). Optimizing drug dosing when patients are in remission (proactive TDM) may be beneficial in certain circumstances. However, frequently the serum drug concentration in isolation becomes the focus TDM. Additionally, the lines of reactive and proactive TDM can quickly blur in many common clinical settings...

Objectives: Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients. Methods: Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months...

Ustekinumab is a monoclonal antibody used in Crohn's disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic-pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity...

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC)...

BACKGROUND & AIMS: Patients with Crohn's disease (CD) treated with ustekinumab who experience inadequate response, or loss of response after standard induction and/or maintenance dosing may benefit from dose escalation. We conducted a systematic review and meta-analysis examining the effectiveness of reinduction and/or dose interval shortening of ustekinumab in patients with active CD despite standard induction and maintenance. METHODS: Through a systematic literature search through March 31, 2021, we identified 15 cohort studies in 925 adults with CD with inadequate response or loss of response to standard dose ustekinumab, underwent dose escalation (reinduction and/or dose interval shortening to <8 weeks), and reported rates of achieving clinical response, corticosteroid-free clinical remission, endoscopic response, and/or remission...

INTRODUCTION: Ustekinumab is a human IgG1 kappa monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23 and blocks the binding of these cytokines to the IL-12Rβ1 chain of their receptors. Ustekinumab is approved for treating moderate-to-severe ulcerative colitis (UC). AREAS COVERED: We reviewed the mechanism of action, pharmacokinetics, efficacy, and safety of ustekinumab. Future challenges for optimizing UC treatment with ustekinumab are discussed...

Psoriasis is a chronic and debilitating inflammatory immune-mediated skin disorder. Several cytokines including interleukin (IL)-23 were demonstrated to play a central role in the pathogenesis of this disease. Treatment options for psoriasis range from topical to systemic modalities, depending on the extent, anatomical locations involved and functional impairment level. Targeting cytokines or their cognate receptors that are involved in disease pathogenesis such as IL-12/23 (i.e., targeting the IL-12p40 subunit shared by these cytokines), IL-17A, IL-17F, IL-17RA, and TNF-α using biologic agents emerged in recent years as a highly effective therapeutic option for patients with moderate-to-severe disease...

BACKGROUND: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. OBJECTIVES: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs...

BACKGROUND: In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma-either ADA dose optimization or switching to vedolizumab or ustekinumab. METHODS: Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4...

Background: Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease...