Glatiramer Acetate for Multiple Sclerosis With Autoimmune Comorbidities

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pilot Study for Evaluation of Glatiramer Acetate in RRMS Patients With Comorbid Autoimmune Conditions

Conditions
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Relapsing Remitting Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Glatiramer Acetate<br>GA administered SQ daily in MS patients who met all Inclusion-Exclusion Criteria and were approved by their Health Care Plans for GA treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Clinical Global Impression Scale (CGI-1). | The primary objective is to determine whether daily GA injections do not aggravate comorbid autoimmune conditions. | Comparison of CGI-1 score pre- and post-treatment.at 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objectives include Visual Analog Scale (VAS). | Comparison of VAS data pre- and post-treatment (Baseline, Mo 3, Mo 6). | Secondary objective will be done at Baseline, Mo 3, Mo 6. | 
| Secondary objectives include Expanded Disability Status Scale (EDSS) | Comparison of EDSS score pre- and post-treatment (Baseline, Mo 3, Mo 6). | Secondary objective will be done at Baseline, Mo 3, Mo 6. | 
| Secondary objectives include concomitant medication review. | Comparison/review of Concomitant Medications used for co-morbid condition treatment (Baseline, Mo 3, Mo 6). | Secondary objective will be done at Baseline, Mo 3, Mo 6. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RRMS, Glatiramer Acetate, Multiple Sclerosis, Autoimmune Comorbidities, Psoriasis, Autoimmune Thyroiditis, Vasculitis, Rheumatoid Arthritis