Glatiramer Acetate for Multiple Sclerosis With Autoimmune Comorbidities
Glatiramer Acetate for Multiple Sclerosis With Autoimmune Comorbidities
The incidence of autoimmune conditions is at least 2-3 times higher in Multiple Sclerosis
 population than in general population. These MS patients category response unfavorably to the
 Interferon. The investigators suggest that autoimmune co morbidity can serve as a biological
 marker predicting good response to GA.
Multiple Sclerosis (MS) is an auto-immune neurodegenerative disease that affects more than
 400,000 individuals in the United States, and 2.5 million worldwide
 (www.nationalmssociety.org). The main pathogenic mechanism in MS involves an inflammatory
 condition that damages the myelin of the central nervous system (CNS), resulting in axonal
 damage and neurological impairment, often leading to severe disability. MS is one of the most
 common causes of neurological disability in young and middle-aged adult individuals, and as
 such has a tremendous physical, psychological and social impact on patients' lives. MS is a
 complex disease diagnosed by McDonald criteria with different clinical and pathological
 phenotypes. Several forms of MS have been described: Relapsing-Remitting (RRMS),
 Secondary-Progressive MS (SPMS), Progressive-Relapsing MS (PRMS), and Primary-Progressive MS
 (PPMS).

 Glatiramer Acetate (GA) and Beta-Interferons (β-IFNs) are well established first-line
 immunomodulating treatment options for relapsing remitting multiple sclerosis (RRMS) with
 excellent safety profiles. The mechanisms of action of GA and IFNs are different. It is well
 known that in general Disease-Modifying Treatments (DMTs) reduce relapse rate in more than
 half of the multiple sclerosis (MS) patients who receive DMT, while having little if any
 effect on the rest. It has been speculated that the response to beta-interferons or GA may
 have genetic basis. As Axtell RC et al. indicated the experimental autoimmune
 encephalomyeilits (EAE) in mouse caused by TH1 cells generally respond well to
 interferon-beta, while EAE caused by TH17 cells get worse with interferon-beta.

 Autoimmune disease is an extreme situation where the autoimmune response overshoots and goes
 out of control. The other extreme is a degenerative disorder, where the autoimmune response
 is not strong enough for effective protection, and degeneration therefore continues. GA being
 an immunomodulator may provide both properly regulated immune suppression (in the case of
 autoimmune disease) and properly regulated immune activation (in the case of the
 neurodegenerative disease).

 Autoimmune conditions cluster in families with high risk for multiple sclerosis than in
 general population which suggests that the disease might arise on a background of a
 generalized susceptibility to autoimmunity. Occurrence of psoriasis, autoimmune thyroiditis,
 vasculitis, rheumatoid arthritis, scleroderma, lupus are seen more commonly in MS patients.
 Many of these patients initially get started on beta-IFNs, and usually do not do well on
 them. According to Investigator's and the USC MS Comprehensive Care Center experience,
 autoimmune co-morbidity associated with MS can serve as a biological marker predicting good
 response to GA and unfavorable response to the IFNs.
Inclusion Criteria:

 -  Clinically definite multiple sclerosis defined by McDonald Criteria.

 -  Between 18-60 years of age.

 -  Subject must able to understand and sign the IRB- approved informed consent form prior
 to the performance of any study-specific procedures and is willing to comply with the
 required scheduling and assessments of the protocol.

 -  Subjects who are women of childbearing potential, must have a negative serum pregnancy
 test at the screening visit, and must be willing to practice a reliable birth-control
 method.

 -  Subjects must have officially diagnosed and documented co-morbid, other than MS,
 autoimmune condition (psoriasis, vasculitis, thyroiditis or rheumatoid arthritis).

 -  At the time of enrollment patients were on beta IFN (Avonex, Betaseron or Rebif)
 treatment for at least 3 months.

 Exclusion Criteria:

 -  Women who are either pregnant or breastfeeding, and women of child-bearing potential
 (defined as not surgically sterile or at least two years postmenopausal) who are not
 using one of the following birth control methods: tubal ligation, implantable
 contraception device, oral, patch, injectable or transdermal contraceptive, barrier
 method or sexual activity restricted to vasectomized partner.

 -  Any clinically significant general health conditions that may interfere with the trial
 participation.

 -  Subject has a history of drug or alcohol abuse within the past year.

 -  Subject had corticosteroid treatment within last 90 days.

 -  Subject started new medication within last 30 days.

 -  Subject is a participant in another research project.

 -  Subject has contraindications for GA treatment.