Diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA)

A technology for rheumatoid arthritis, applied in the direction of chemical instruments and methods, biochemical equipment and methods, pharmaceutical formulations, etc., can solve problems such as improved diagnosis and treatment methods are not met

Pending Publication Date: 2020-09-04
GENENTECH INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the heterogeneity of RA, predicting which individuals will best benefit from different treatment modalities has been challenging
[0007] Therefore, there is an unmet need for improved diagnostic and therapeutic methods for treating individuals with RA

Method used

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  • Diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA)
  • Diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA)
  • Diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0308] Example 1. Correlation Between Immunohistochemical (IHC) Lesion Patterns and Gene Expression Levels in Individuals with Rheumatoid Arthritis (RA)

[0309] Ultrasound-guided synovial biopsies collected from a cohort of 129 individuals were included in the Early Arthritis Pathology Cohort (PEAC), a treatment-naïve, early-stage rheumatoid arthritis (RA) patient population characterized by duration of symptoms less than 12 months. Perform histological analysis and gene expression microarray experiments on isolated synovial tissue to identify lesion-specific cellular and gene expression markers, assess associations between gene expression patterns and disease progression, and identify genes for prognostic and predictive purposes potential biomarkers.

[0310] Research design

[0311] 144 RA individuals meeting the 2010 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for RA were enrolled in the Barts Health National ...

Embodiment 2

[0338] Example 2. Association Between Lesion Type, Gene Expression Levels, Clinical Covariates, Disease Activity, and Disease Progression in Individuals with RA

[0339] Associations of synoviopathic type and gene expression levels with clinical covariates were assessed to determine whether they predicted disease activity and / or progression in individuals with RA.

[0340] Synovial lesion type and gene expression predict radiographic progression

[0341] Association of baseline lesion type or gene expression with ongoing structural damage as measured by the Sharp-van der Heijde radiographic progression score (ShSS) 12 months after the initial biopsy was assessed. Although the baseline lesion pattern did not predict erosion or joint space narrowing at 12 months, lymphoid individuals had significantly higher increases in ShSS and a greater risk of progressive disease (>1ΔShSS) compared to myeloid and pauci-immune fibrotic individuals ( Figure 5A ). Importantly, of the 16 indi...

Embodiment 3

[0350] Example 3. Association Between Myeloid and Lymphatic Signature Gene Scores and Response to DMARD Therapy

[0351] As discussed in Example 2, lesion-specific signature gene scores correlated with disease activity and progression. The association of lesion-specific signature gene scores with individual responsiveness to DMARD therapy was further assessed and whether they could be used as biomarkers to predict and / or monitor responsiveness to DMARD therapy.

[0352] Association of Pretreatment Lesion Type and Gene Expression Levels with Response to DMARD Treatment

[0353] Individuals with three different histologically defined lesion types were compared for response to DMARD therapy as determined by changes in DAS28-ESR and EULAR response criteria at six months. No significant association between baseline lesion status and treatment outcome was observed, but it is noteworthy that myelo- and lymphopathic individuals were treated more frequently with combinations of methot...

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Abstract

The present invention provides prognostic, predictive, and therapeutic methods for the treatment of rheumatoid arthritis (RA). The invention is based, at least in part, on the discovery that the expression level of one or more biomarkers described herein in a sample (e.g., a synovial tissue sample, a synovial fluid sample, or a combination thereof) from an individual having RA can be used in methods of determining whether an individual having RA is likely to exhibit disease progression, identifying an individual having RA who is likely to respond to a treatment including a disease modifying anti-rheumatic drug (DMARD), predicting responsiveness of an individual having RA to a treatment including a DMARD, selecting a therapy for an individual having RA, and treating an individual having RA,as well as related kits.

Description

[0001] sequence listing [0002] This application contains a Sequence Listing, which has been filed electronically in ASCII format, and is hereby incorporated by reference in its entirety. Said ASCII copy was created on January 22, 2019, is named 50474-175WO2_Sequence_Listing_1.22.19_ST25, and is 93,444 bytes in size. technical field [0003] The present invention relates to diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA). In particular, the invention provides methods for predicting disease progression and activity, methods for predicting response to therapy, methods for monitoring responsiveness to therapy, methods for selecting therapy, methods of treatment, and diagnostic kits. Background technique [0004] Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by symmetrical joint involvement, inflammation, synovial lining hyperplasia, and infiltrating granulation tissue formation. If left unchecked, the d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883
CPCC12Q1/6883C12Q2600/106C12Q2600/118C12Q2600/158A61K31/519A61P19/02C07K16/2866C07K16/2887
Inventor M·刘易斯C·皮萨利斯N·拉马穆尔西M·J·汤森J·哈克尼
Owner GENENTECH INC
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