Method for treating joint damage

Abstract

Methods of treating joint damage in a subject eligible for treatment are provided involving administering an antagonist that binds to a B-cell surface marker, such as CD20 antibody, to the subject in an amount effective to slow progression of the joint damage as measured by radiography. Further provided are articles of manufacture useful for such methods.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a National Stage application filed under 35 USC § 371 of PCT Application No. PCT / US2006 / 044290, filed Nov. 14, 2006, which claims the benefit of priority under 35 U.S.C. §119(e) of provisional application Nos. 60 / 864,463, filed Nov. 6, 2006, and 60 / 737,291, filed Nov. 15, 2005. The contents of each application listed in this paragraph are fully incorporated by reference herein.FIELD OF THE INVENTION[0002]The present invention concerns methods for treating joint damage in subjects suffering therefrom.BACKGROUND OF THE INVENTIONJoint Destruction and Damage[0003]Inflammatory arthritis is a prominent clinical manifestation in diverse autoimmune disorders including rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), Sjögren's syndrome and polymyositis. Most of these patients develop joint deformities on physical examination but typically only RA and PsA patients manifest bone erosions o...

AI Technical Summary

Benefits of technology

[0047]The present invention involves administration of a CD20 antagonist that provides a safe and active treatment regimen in subjects with joint damage, including selection of an efficacious dosing regimen and scheduled or unscheduled re-treatment. This antagonist is effective both in initial therapy and in the management of refractory disease.

Problems solved by technology

Joint Destruction and Damage

It is a systemic inflammatory disease characterized by chronic inflammation in the synovial membrane of affected joints, which ultimately leads to loss of daily function due to chronic pain and fatigue.

The majority of patients also experience progressive deterioration of cartilage and bone in the affected joints, which may eventually lead to permanent disability.

The long-term prognosis of RA is poor, with approximately 50% of patients experiencing significant functional disability within 10 years from the time of diagnosis.

Such diseases are accompanied by bone loss around affected joints due to increased osteoclastic resorption.

There is loss of articular cartilage and the formation of bony erosions.

Ultimately, the integrity of the joint structure is compromised, producing disability.

However, the progression rates in individuals within the treatment and control groups overlap to a considerable extent; therefore, despite significant differences between treatment groups, these data cannot be used to estimate the probability that a patient who is starting a treatment will have a favorable outcome with respect to progression of radiographic damage.

Determining whether there has been increased structural damage in an individual patient during the interval between paired radiographs obtained at the beginning and end of a 6- or 12-month clinical trial has been difficult, for several reasons.

The rate of radiographic damage is not uniform within a population of RA patients; a few patients may have rapidly progressing damage, but many may have little or no progression, especially if the tie interval is relatively short.

If the reader is blinded to the temporal sequence of the films, these unavoidable scoring errors may be in either direction, leading to apparent “healing” when the score decreases or to apparent rapid progression when reading error increases the difference between films.

The imprecision of the clinical measures that are used to quantitate RA disease activity has caused a similar problem; statistically significant differences between certain outcome measures from clinical trials were not useful for estimating the probability of improvement for an individual who was starting the treatment (Paulus et al., Arthritis Rheum., 33: 477-484 (1990)).

Although several DMARDs are initially clinically effective and well tolerated, many of these drugs become less effective or exhibit increased toxicity over time.

Despite the advances in treatment of joint disease, a significant number of patients do not qualify for, are intolerant of, or experience an insufficient response to current treatments.

Images