Efficacy and safety of subcutaneous abatacept + standard treatment for active idiopathic inflammatory myopathy: phase III randomised controlled trial.

Objective: To evaluate the efficacy and safety of subcutaneous (SC) abatacept and standard of care (SOC) for the treatment of idiopathic inflammatory myopathy (IIM) over 52 weeks.

Methods: In this randomised, double-blind, placebo-controlled phase III trial, patients with treatment-refractory IIM received SC abatacept (125 mg weekly) + SOC (abatacept group) or placebo + SOC (placebo group) (NCT02971683). A 24-week double-blind period was followed by an open-label period to assess outcomes from continued therapy with abatacept and initiation with abatacept (placebo-to-abatacept switch group) from 24 to 52 weeks.

Abatacept increases T cell exhaustion in early RA individuals who carry HLA risk alleles.

Exhausted CD8 T cells (T) are associated with worse outcome in cancer yet better outcome in autoimmunity. Building on our past findings of increased TIGITKLRG1 T with teplizumab therapy in type 1 diabetes (T1D), in the absence of treatment we found that the frequency of TIGITKLRG1 T is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. This TIGITKLRG1 CD8 T population shares an exhaustion-associated EOMES gene signature in HC, T1D, rheumatoid arthritis (RA), and cancer subjects, expresses multiple inhibitory receptors, and is hyporesponsive , together suggesting co-expression of TIGIT and KLRG1 may broadly define human peripheral exhausted cells.

Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies.

Objectives: This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA).

Methods: This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.

Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC.

ACPA-negative and ACPA-positive RA patients achieving disease resolution demonstrate distinct patterns of MRI-detected joint-inflammation.

Objectives: Although sustained DMARD-free remission (SDFR; sustained absence of clinical-synovitis after DMARD-discontinuation) is increasingly achievable in RA, prevalence differs between ACPA-negative (40%) and ACPA-positive RA (5-10%). Additionally, early DAS remission (DAS4months<1.6) is associated with achieving SDFR in ACPA-negative, but not in ACPA-positive RA.

Urinary CD80 Discriminates Among Glomerular Disease Types and Reflects Disease Activity.

Introduction: Heterogeneity of nephrotic diseases and a lack of validated biomarkers limits interventions and reduces the ability to examine outcomes. Urinary CD80 is a potential biomarker for minimal change disease (MCD) steroid-sensitive nephrotic syndrome (NS). We investigated and validated a CD80 enzyme-linked immunosorbent assay (ELISA) in urine in a large cohort with a variety of nephrotic diseases.

Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE).

Introduction: Patients with rheumatoid arthritis (RA) with poor prognostic factors, such as seropositivity for anti-citrullinated protein antibodies and early erosions, may benefit from early intensive treatment. However, information to guide physicians on the best choice of therapy in these patients is limited. The objective of this study was to describe the efficacy of subcutaneous abatacept versus adalimumab over 2 years in patients with seropositive, erosive early RA in the AMPLE study.

Relationship Between Middle Ear Volume and Long-term Audiological Outcomes in Congenital Aural Atresia Repair.

Objective: To assess the association of middle ear volume with long-term hearing outcomes in congenital aural atresia (CAA) repair.

Study Design: Retrospective chart and radiological review.

Setting: Single academic tertiary referral center.

Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study.

Objectives: To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726).

Methods: Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.

Spinal Hematomas: What a Radiologist Needs to Know.

Spinal hematomas are a frequent indication for radiologic evaluation and can be a diagnostic dilemma for many radiologists and surgeons. There are four types of spinal hematomas: epidural, subdural, subarachnoid, and intramedullary (spinal cord) hematomas. Because they differ by their location in relationship to the meningeal membranes and spinal cord, unique radiologic appearances can be recognized to distinguish these types of spinal hemorrhage.

Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome.

Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration-approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings.

Imaging of pediatric neurovascular emergencies.

Pediatric strokes are rare but critical diagnoses to make in the emergency setting. They are associated with a set of pathologies that are not frequently encountered in the adult population. Some of these diseases have variable clinical presentations and imaging appearance depending on the age of onset and severity of the underlying pathologies.

Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab.

Objective: To assess the ability of a multi-biomarker disease activity (MBDA) test (Vectra DA) to reflect clinical measures of disease activity in patients enrolled in the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial.

Methods: In the AMPLE trial, patients with active rheumatoid arthritis (RA) who were naive to biologic agents and had an inadequate response to methotrexate were randomized (1:1) to receive subcutaneous abatacept (125 mg every week) or subcutaneous adalimumab (40 mg every 2 weeks), with background methotrexate, for 2 years. The MBDA score was determined using serum samples collected at baseline, month 3, and years 1 and 2.

Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration.

Objectives: To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial.

Methods: Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.

Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis.

Objective: To report 2-year patient-reported outcomes (PROs) from the head-to-head Abatacept versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate (MTX) (AMPLE) trial.

Methods: AMPLE was a phase IIIb, randomized, investigator-blinded trial. Biologic-naive patients with rheumatoid arthritis (RA) and an inadequate response to MTX were randomized to subcutaneous (SC) abatacept (125 mg/week) or adalimumab (40 mg every 2 weeks) with background MTX.

Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial.

Objectives: To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study.

Methods: In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates.

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial.

Objectives: To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA).

Methods: AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX.

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study.

Objective: There is a need for comparative studies to provide evidence-based treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore, this study was undertaken as the first head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA.

Methods: Patients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both given in combination with MTX, in a 2-year study.

Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice.

CD59 is a GPI-anchored membrane regulator of complement expressed on blood cells as well as peripheral tissues. It protects host cells from complement injury by inhibiting formation of the membrane attack complex. Recent studies in mice have suggested also a role of CD59 in T cell immune response that was mechanistically independent of complement.

RANTES deficiency attenuates autoantibody-induced glomerulonephritis.

Experimental autoimmune nephritis in mice and spontaneous lupus nephritis are both associated with elevated expression of several chemokines in the kidneys. Nevertheless, the role that different chemokines play in mediating renal inflammation is far from complete. This study focuses on elucidating the functional role of RANTES, a chemokine that has been noted to be hyper-expressed within the kidneys, both in experimental renal disease as well as in spontaneous lupus nephritis.