Methods relating to anti-IL-1 therapy and anti-IL-6 therapy and hypersensitivity
Inventors
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Assignees
University of California, San Diego • Leland Stanford Junior University
MemberStanford UniversityStanford UniversityTodd Coleman is an associate professor of bioengineering at Stanford University. His research combines applied probability, physiology, and bioelectronics to develop methods and devices for monitoring and modulating nervous-system and other physiological activity, including brain and visceral-organ signals.
Todd Coleman is an associate professor of bioengineering at Stanford University. His research combines applied probability, physiology, and bioelectronics to develop methods and devices for monitoring and modulating nervous-system and other physiological activity, including brain and visceral-organ signals.
Publication Number
US-12753443-B2
Publication Date
2026-10-06
Expiration Date
Abstract
Provided herein are, inter alia, methods for treating subjects in need of an IL-1 inhibitor therapy or an IL-6 inhibitor therapy, and related methods. The methods include determining whether the subject is at risk for drug-related hypersensitivity by assaying for the presence of certain HLA alleles.
Core Innovation
The disclosure identifies HLA-DRB1*15, particularly HLA-DRB1*15:01, HLA-DRB1*15:03, and HLA-DRB1*15:06, and linked HLA-DRB5*01:01 as genetic risk markers for delayed hypersensitivity reactions associated with anti-IL-1 and anti-IL-6 therapies. Documented adverse reactions include drug reaction with eosinophilia and systemic symptoms, atypical rash, diffuse lung disease, and macrophage activation syndrome. In reported cohorts, the identified HLA-DRB1*15 alleles are present in about 75% of reaction cases and absent from drug-tolerant controls across multiple therapeutic inhibitors.
The claimed method detects an HLA-DRB1*15 or HLA-DRB5*01:01 allele in a subject receiving, or in need of, anti-IL-1 or anti-IL-6 therapy to guide clinical decisions. For subjects receiving therapy, detection guides treatment discontinuation, dose or administration frequency reduction, or combination therapy. For subjects in need of therapy, detection guides selection of an alternative therapeutic regimen to reduce hypersensitivity risks during inflammatory disease treatment.
Claims Coverage
The claim identifies four inventive features spanning allele detection, treatment adjustment, alternative therapy selection, and specified therapies and disease settings.
Detection of HLA alleles
Detecting an HLA-DRB1*15 allele or HLA-DRB5*01:01 allele in a biological sample of a subject receiving, or in need of, anti-IL-1 or anti-IL-6 therapy. Dependent claims specify HLA-DRB1*15:01, HLA-DRB1*15:03, or HLA-DRB1*15:06.
Treatment adjustment for a subject receiving therapy
For a subject receiving anti-IL-1 or anti-IL-6 therapy, the claim provides for discontinuing the therapy, administering an altered dose or reduced administration frequency, or administering the therapy in combination with an additional therapy such as methotrexate, a corticosteroid, or a DMARD.
Alternative therapy for a subject in need of treatment
For a subject in need of anti-IL-1 or anti-IL-6 therapy, the claim provides for administering an alternative therapy comprising one or more of intravenous gamma globulin (IVIG), a calcineurin inhibitor (such as cyclosporine or tacrolimus), a Janus kinase (JAK) inhibitor, a TNF inhibitor, a corticosteroid, a T-cell inhibitor, or an IL-5 inhibitor.
Specified therapies and inflammatory diseases
The claim identifies anakinra, canakinumab, rilonacept, tocilizumab, sarilumab, or satralizumab as anti-IL-1 or anti-IL-6 therapies. It specifies subjects with systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), Kawasaki disease (KD), polyarthritis, rheumatoid arthritis, undifferentiated autoinflammatory disorder, giant cell arteritis, or COVID-19 related cytokine storm.
The claim covers detecting specified HLA alleles and using the result to guide treatment continuation, modification, combination, or alternative therapy across defined therapeutic agents and autoinflammatory conditions.
Stated Advantages
The disclosed approach aims to reduce delayed hypersensitivity risk while treating inflammatory disease.
The findings support considering pre-prescription HLA risk assessment and monitoring for delayed reactions.
Documented Applications
The claimed method is directed to treatment decisions for subjects receiving or in need of anti-IL-1 or anti-IL-6 therapy for systemic juvenile idiopathic arthritis, adult-onset Still's disease, Kawasaki disease, polyarthritis, rheumatoid arthritis, undifferentiated autoinflammatory disorder, giant cell arteritis, or COVID-19 related cytokine storm.
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