Methods of treating inflammatory and autoimmune diseases with natalizumab
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Publication Number
US-9493567-B2
Publication Date
2016-11-15
Expiration Date
Abstract
Natalizumab is a safe and efficacious treatment for inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, and rheumatoid arthritis. Rare occurrences of progressive multifocal leucoencephalopathy during treatment suggest the possibility that it may be related to natalizumab treatment. Monitoring for JCV and informing caregivers and patients about the manifestations of progressive multifocal leucoencephalopathy can improve the safety of natalizumab therapy.
Core Innovation
The problem addressed is the safety of natalizumab treatment in a patient with an inflammatory or autoimmune disease, because progressive multifocal leukoencephalopathy (PML) can occur during natalizumab therapy. The disclosed approach monitors for PML risk and indicators in a structured manner in connection with natalizumab use, including identifying risk associated with JC virus (JCV) and using monitoring that leads to either continuation or discontinuation of natalizumab based on the presence or absence of PML indicators.
The disclosed method tests a patient for anti-JC virus (JCV) antibodies by measuring the presence of anti-JCV antibodies in the serum or plasma of a blood sample. Treatment with natalizumab is initiated when the sample is negative for anti-JCV antibodies. After natalizumab initiation, the method includes testing the patient for indicators of PML by detecting the presence of JCV in cerebrospinal fluid, and/or by detecting clinical and/or radiologic symptoms of PML.
The disclosed approach further requires a decision point for further administration of natalizumab based on the results of PML indicator testing. Natalizumab is further administered in the absence of indicators of PML, and natalizumab treatment is discontinued in the presence of indicators of PML. The document supports this workflow with description of PML occurrence during natalizumab trials and with safety evaluation using criteria involving MRI and cerebrospinal fluid JCV DNA.
Claims Coverage
The disclosed independent claim describes a multi-step treatment-monitoring method with three inventive decision points: anti-JCV antibody testing to guide natalizumab initiation, PML indicator testing to guide ongoing natalizumab administration, and conditional continuation versus discontinuation of natalizumab based on those PML indicators. Dependent claims further refine the disease scope and the types of clinical and radiologic PML indicators considered.
Anti-JCV antibody testing for natalizumab initiation
Testing the patient for the presence of anti-JC virus (JCV) antibodies by measuring the presence of anti-JCV antibodies in the serum or plasma of a blood sample from the patient.
Natalizumab administration when anti-JCV antibodies are negative
Initiating treatment by administering natalizumab to the patient in the event the sample is negative for anti-JCV antibodies.
PML indicator detection via cerebrospinal fluid JCV and/or clinical/radiologic symptoms
Testing the patient for indicators of progressive multifocal leukoencephalopathy (PML) by detecting the presence of JCV in the patient's cerebrospinal fluid, or detecting clinical and/or radiologic symptoms of PML in said patient.
Conditional further administration or discontinuation based on PML indicators
Further administering natalizumab to the patient in the absence of indicators of PML or discontinuing natalizumab treatment in the presence of indicators of PML.
Inflammatory bowel disease application
The method applied to treating inflammatory bowel disease.
Crohn’s disease selection
Wherein the inflammatory bowel disease is Crohn's disease.
Gd-enhanced MRI lesion radiologic symptoms as PML indicators
The radiologic symptoms include lesions detected by a Gd-enhanced magnetic resonance imaging (MRI) scan.
Neurological symptom set as PML indicators
Wherein the neurological symptoms include central blindness, mental confusion, personality change, and dyskinesia.
Multiple sclerosis subtype selection
Wherein the multiple sclerosis is chosen from relapsing-remitting, secondary progressive, primary progressive, or chronic progressive types.
Overall, the claim coverage is centered on a treatment workflow that starts with anti-JCV antibody testing, proceeds to natalizumab initiation when anti-JCV antibodies are negative, and then uses cerebrospinal fluid JCV and/or clinical and radiologic PML indicators to decide whether to further administer natalizumab or discontinue it. Dependent claims narrow the disease scope, including inflammatory bowel disease and Crohn's disease, and refine the PML indicator criteria to include specified neurological symptoms and Gd-enhanced MRI lesion findings, as well as multiple sclerosis subtype selection.
Stated Advantages
Enables safer natalizumab use by monitoring for progressive multifocal leukoencephalopathy (PML) risk and indicators and using those results to inform continuation or discontinuation of natalizumab.
Documented Applications
Treating a patient with an inflammatory or autoimmune disease using a natalizumab approach that includes anti-JCV antibody testing and PML monitoring based on cerebrospinal fluid JCV and/or clinical/radiologic symptoms.
Use in multiple sclerosis, Crohn’s disease, and rheumatoid arthritis as described in the document.
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