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Summary of Accomplishments of LIC-supported studies

As of December 2019

Determinants of ANA Expression in Patients with Lupus PI: David Pisetsky (Duke University)

Co-PIs: Megan Clowse (Duke University), Peter Lipsky (AMPEL BioSolutions LLC), Dr. Brad Rovin, Ohio State University

Project Status: Completed in 2018

The goal of this study was to assess the expression of antinuclear antibodies (ANA) in SLE, focusing on the frequency of ANA negativity in patients with established disease.

Summary of Accomplishments: The study demonstrated that in 103 patients with established SLE the frequency of ANA negativity varied widely from 5% to 23% depending on the assay platform and kit used to measure the antibodies. The findings also showed a difference between the patient samples that tested ANA positive in all assays from those that were discordant across assays. Specifically, the consistently ANA positive samples had higher likelihood of historical anti-dsDNA positivity and a lower level of complement component C3 compared to the ANA discordant samples.

The results of this study were published in the Annals of Rheumatic Diseases and a related letter was published in Arthritis Care & Research.

LIC-OMERACT Partnership to Advance SLE Outcome Measures

Executive Committee: John Esdaile (Arthritis Research Centre of Canada), Matthew Liang (Harvard Medical School), Peter Lipsky (AMPEL BioSolutions LLC), Rosalind-Ramsey-Goldman (Northwestern University), Lee Simon (SDG LLC), Vibeke Strand (Stanford University), Margaret Dowd (LRA)

Project Status: LIC-funded Project completed; further validation of the instrument supported by the LRA is ongoing and should be completed by end of 2020.

The long-term objective of the project is to propose and then validate new outcome measure(s) for trials of new treatments in SLE by developing Multi-dimensional Response Indices (MRI) with better ‘responsiveness to change’ than the conventional outcome measures, such as SRI used in recent SLE trials.

Summary of Accomplishments: Together with OMERACT, the LIC has recently developed a Lupus Multivariable Outcome Score (LuMOS) based on the contrast between outcomes in the Belimumab (BM) 10 mg/kg (n=273) versus Placebo (n=275) subgroups in the BLISS-76 trial (Furie et. al. A&R 2012) and validated using an independent dataset, from the BLISS-52 trial. The LuMOS development and initial validation was published in Arthritis & Rheumatology. Additional validation of LuMOS was conducted by Astra Zeneca (AZ) using the data from the Phase 2b Anifrolumab lupus trial; the results were presented by AZ at the July 2018 LIC meeting.

LRA is currently supporting the further validation of LuMOS. Specifically, the goals of the ongoing effort are to 1) Enhance the current LuMOS model by including PROs, avoiding reliance on SLEDAI/BILAG, and other improvements; and 2) Validate the original and the improved

LuMOS instruments and compare their performance with the existing SLE outcome measures in new data sets including the one from Tabalumab’s ILLUMINATE 1 and 2 trials.

There are ongoing efforts to secure additional data sets especially from trials targeting pathways other than BAFF.

Dynamic Imaging of Variation in Lupus Nephritis (DIVINE) PI: Peter Lipsky (AMPEL BioSolutions LLC)

Co-PIs: David Karp (University of Texas Southwestern) and Brad Rovin (Ohio State University)

Project Status: Recruitment completed analysis ongoing; anticipated completion – end of 2020

The goal of this study is to develop a multi-modality imaging approach for the evaluation of the pathologic changes in Lupus Nephritis (LN). To use a variety of renal imaging modalities, including diffusion weighted imaging (DWI), blood oxygen level dependent (BOLD) imaging, T1rho (T1rho) imaging, and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to evaluate the intra-renal blood flow, perfusion, cellularity, fibrosis and atrophy within the kidneys of patients with lupus nephritis (LN) and compare these parameters to renal biopsy findings to determine whether DWI, BOLD, T1rho, and DCE- MRI may provide a set of non-invasive tools to assess renal function and pathology in LN.

Summary of Accomplishments: The clinical study (NCT03180021) has completed recruitment with 21 subjects enrolled. Thus far, nine subjects have been evaluated and their imaging data has been assessed for quality. These results were presented at the 2019 ACR meeting (Abstract #1919). The findings thus far suggest the following according to the abstract presentation: “These initial results have established the feasibility of multi-modality imaging as a tool to evaluate LN in a multi-center study. Moreover, changes in perfusion detected by DCE-MRI significantly correlate with proteinuria and urinary protein:creatinine ratio.” The analysis of the rest of the study cohort is expected to be completed by the end of 2020.

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