Rocatinlimab: A Novel T-Cell Rebalancing Therapy Targeting the OX40 Receptor in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by eczematous skin lesions, intense pruritus, skin pain, sleep disruption, and mental health disturbances. There remains a need for a therapeutic option that delivers durable efficacy, safety, and convenient dosing across the AD patient population. This review provides an overview of AD pathogenesis driven by T-cell imbalance and describes a novel therapeutic option targeting the OX40 receptor, a costimulatory molecule expressed specifically on activated T cells.

ROCKET: a phase 3 program evaluating the efficacy and safety of rocatinlimab in moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease affecting ~ 10% of adults and ~ 20% of children globally. Many patients with moderate-to-severe AD receiving systemic therapies, including biologics and Janus kinase (JAK) inhibitors, fail to reach or maintain treatment goals due to lack of durable response or safety/tolerability issues. Rocatinlimab is a T-cell rebalancing therapy that inhibits and reduces pathogenic T cells by targeting the OX40 receptor.

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase 2b Study.

Introduction: In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase 2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs).

Methods: This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI).

Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab.

In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck.

Content evaluation of pruritus, skin pain and sleep disturbance patient-reported outcome measures for adolescents and adults with moderate-to-severe atopic dermatitis: qualitative interviews.

Background: Pruritus, skin pain and sleep disturbance place a significant burden on individuals with moderate-to-severe atopic dermatitis (AD) and negatively affect their quality of life. Fit-for-purpose patient-reported outcome measures (PROMs) that assess AD-related pruritus, skin pain and sleep disturbance are important for evaluating the effectiveness of new AD treatments.

Objectives: To evaluate the content validity of five AD-related PROMs in adolescents and adults with moderate-to-severe AD [the Worst Pruritus Numeric Rating Scale (NRS), the AD Skin Pain NRS, the Sleep Disturbance NRS, the skin pain-specific Patient Global Impression of Change (PGIC) and the skin pain-specific Patient Global Impression of Severity (PGIS)], and to assess patient-reported experience with pruritus, skin pain and sleep disturbance.

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD.

An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study.

Background: OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis.

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Dose and Multiple-Rising-Dose Study of the BTK Inhibitor TAK-020 in Healthy Subjects.

Bruton's tyrosine kinase (BTK) is a target for treatment of hematologic malignancies and autoimmune diseases. TAK-020 is a highly selective covalent BTK inhibitor that inhibits both B cell receptor and fragment crystallizable receptor signaling. We assessed the safety/tolerability and pharmacokinetics/pharmacodynamics (PDs) of TAK-020 in healthy subjects.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients.

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation.

Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis.

Objectives: Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA).

Methods: Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.

Induction of cartilage integration by a chondrocyte/collagen-scaffold implant.

The integration of implanted cartilage is a major challenge for the success of tissue engineering protocols. We hypothesize that in order for effective cartilage integration to take place, matrix-free chondrocytes must be induced to migrate between the two tissue surfaces. A chondrocyte/collagen-scaffold implant system was developed as a method of delivering dividing cells at the interface between two cartilage surfaces.

TRACP Influences Th1 pathways by affecting dendritic cell function.

Unlabelled: TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo.