Methods of treating inflammatory and autoimmune diseases with natalizumab

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.

Description

PRIORITY CLAIM [0001] This application claims priority to U.S. Provisional Patent Application No. 60 / 776,931,. filed Feb. 28, 2006, which is hereby incorporated herein for all purposes.TECHNICAL FIELD [0002] The invention relates to methods of treating inflammatory and autoimmune diseases with a recombinant antibody. These methods improve the safety of treatment by informing and monitoring patients undergoing antibody treatment. BACKGROUND ART [0003] The migration of lymphocytes from the peripheral blood across the blood brain barrier has been reported to initiate the development of several central nervous system (CNS) inflammatory diseases. Lymphocyte entry into the CNS is mediated by cellular adhesion molecules (O'Neill et al., Immunology 72:520-525 (1991); Raine et al., Lab. Invest. 63:476-489 (1990); Yednock et al., Nature 356:63-66 (1992); Baron et al., J. Exp. Med. 177:57-68 (1993); Steffen et al., Am. J. Path 145:189-201 (1994); Christensen et al., J. Immunol. 154:5293-5301 (...

AI Technical Summary

Benefits of technology

The invention provides safer methods for using natalizumab to treat inflammatory and autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. The methods involve monitoring the patient for indicators of progressive multifocal leukoencephalopathy, a potentially lethal brain disease caused by JCV, and discontinuing the administration of natalizumab if indicators are detected. The monitoring can include testing for JCV in the patient's urine, blood, and cerebrospinal fluid. The invention also provides methods for using natalizumab in combination with other immunosuppressive or antineoplastic agents.

Problems solved by technology

Most individuals present with the relapsing-remitting form of the disease and experience recurrent attacks, which, over time, result in accumulating permanent physical disability and cognitive decline.

Current treatments are minimally effective for secondary progressive MS.

The development of neutralizing antibodies to interferons is associated with a loss of efficacy.

As a result, in the United States alone, over 50,000 patients who were previously treated no longer receive therapy.

Thus, there is a large group of patients with active MS who are currently not receiving any approved therapy.

Although a variety of therapeutic strategies are currently used in clinical practice to manage breakthrough disease while on treatment (e.g., switching therapy, changing dose and frequency of interferon, combination therapy), the similar efficacy between available medications and lack of clinical data demonstrating the effectiveness of any of these strategies in breakthrough patients makes the decision of what to do for these patients largely empirical.