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In an article reporting the 18-month results of the Immune Tolerance Network’s (ITN) RAVE clinical trial, published August 1st in the New England Journal of Medicine, the ITN is providing unfettered access to the underlying clinical data and analysis code via the new clinical trials research portal, ITN TrialShare (itntrialshare.org). The data published today come from the ITN’s RAVE study led by John Stone, MD (Massachusetts General Hospital) and Ulrich Specks, MD (Mayo Clinic). The researchers demonstrated that a single course of rituximab therapy (anti-CD20; Rituxan, Genentech, Inc.) is as effective as the current standard of care regimen of drugs for remission induction and maintenance in patients with ANCA-associated Vasculitis (AAV). Rituximab has a shorter and simpler treatment course compared to standard therapy (cyclophosphamide), as well as an improved safety profile, thus offering significant treatment advancement for patients with AAV. This publication is the first to provide public access to the raw study data via direct links from the publication and its figures to the data sets in TrialShare. The accompanying editorial in NEJM highlights the utility of TrialShare in data sharing and transparency.

The Immune Tolerance Network’s (ITN’s) IMPACT Study, “Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children,” opened for enrollment today. This will be the first major study to examine whether oral immunotherapy can lead to durable, lasting tolerance to peanut among young peanut-allergic children. This study will be led by ITN investigator Wesley Burks, MD, Chair of the Department of Pediatrics at UNC Chapel Hill. Patients will be enrolled at UNC as well as at additional sites around the country including the University of Arkansas, Stanford University, Johns Hopkins Children’s Hospital and Mount Sinai Hospital.

Primary results from the Immune Tolerance Network’s AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes) were published online today in Diabetes. The Phase II AbATE study, led by Kevan Herold, MD (Yale University), tested two doses of anti-CD3 given one year apart in new onset type 1 diabetics compared to control. After 2 years, the anti-CD3-treated group showed significantly greater preservation of C-peptide compared to the control group (75% higher responses compared to control), meeting the study’s primary endpoint.

In a letter published recently in the Journal of Allergy and Clinical Immunology, Immune Tolerance Network (ITN) investigators describe the experience of the ITN’s GPAC study (Immunoprophylaxis of Allergic Disease) that aimed to test whether early intervention with a form of oral immunotherapy in at-risk young children could prevent the development of asthma. Evidence suggests that environmental exposure to allergens early on in life via inhalation and mucosal exposure can induce regulatory (vs. inflammatory) responses towards those allergens. The aim of this study was to test the ability of a sublingual allergen mixture (compared to placebo) to enhance mucosal exposure to certain aeroallergens in very young children at high risk for allergy, possibly arresting the development of inflammatory responses and preventing the onset of allergic disease.

Data from three ITN type 1 diabetes trials will be featured during the “Clinical Trials of T Cell Therapeutics for Reversing Type 1 Diabetes” session at the Annual American Diabetes Association (ADA) Scientific Sessions in Chicago, IL. This session will take place on June 22 from 8:00am-10:00am CT.

In a manuscript published this week in Arthritis & Rheumatism, Immune Tolerance Network (ITN) investigators sought to better understand the distinction between patients who did and did not achieve the primary endpoint in the RAVE Study (Rituximab for the Treatment of ANCA-Associated Vasculitis and Microscopic Polyangiitis). The RAVE study established rituximab (Rituxan®; Genentech), a B-cell depletor, as a treatment alternative to cyclophosphamide (standard of care) for remission induction in patients with ANCA-Associated Vasculitis (AAV), a severe autoimmune disease marked by certain type of antibody (ANCA) that targets the blood vessels. Although outcomes for patients with AAV have improved over the past decades, about a quarter of patients fail standard induction regimens due to persistent or recurrent disease. The current study sought to better understand characteristics that predicted outcomes at 6 months.

Sandy Feng, MD, PhD (University of California, San Francisco) will present 5-year follow-up data on tolerant patients from the Immune Tolerance Network’s (ITN’s) WISP-R study, “Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients” next week at the annual American Transplant Congress (ATC) meeting in Seattle, WA. The talk will report on donor-specific antibody (DSA) in relation to 5-year outcomes.  The primary results from the WISP-R study were reported last year in The Journal of the American Medical Association.

A letter published today in the New England Journal of Medicine reports on the long-term outcomes of patients from two ITN-sponsored combined kidney and bone marrow transplantation studies led by David H. Sachs, MD (Massachusetts General Hospital), Tatsuo Kawai, MD, PhD (Massachusetts General Hospital), Megan Sykes, MD (Columbia University) and A. Benedict Cosimi, MD (Massachusetts General Hospital). The goal of these studies was to create recipient tolerance of the donor kidney by first creating a temporary donor-host “chimeric” immune system via hematopoietic stem cell transplant. The first study enrolled five patients, and a subsequent (slightly modified) study enrolled another five patients.

The quantification of mature T cell subsets is an important prognostic marker for understanding disease. Killer T cells and Helper T cells, characterized by the expression of cell surface marker proteins CD8 or CD4, respectively, effect different aspects of the adaptive immune system, and the ratio of these two populations can reveal important information about the state of the immune system. In a manuscript published recently in the Journal of Immunological Methods, ITN researchers worked with Adaptive Biotechnologies to conduct high-throughput deep sequencing of T cell receptors (TCRs) using their ImmunoSEQ^TM platform.

Three abstracts from the ITN’s RAVE study (Rituximab for the Treatment of ANCA-Associated Vasculitis and Microscopic Polyangiitis) led by John Stone, MD (Massachusetts General Hospital) and Ulrich Specks, MD (Mayo Clinic) were presented this week by the RAVE team at the 16^th International Vasculitis & ANCA Workshop in Paris, France. These abstracts include.