Monoclonal Antibodies: Treatments in Development for MS
In Monoclonal Antibodies: What Are They? we discussed a little bit about how T-cells and B-cells function within the immune system and how medications have been created to target specific antigens on those same lymphocytes. If you haven’t read it, I recommend that you read that post first and then come back to this one.
What monoclonal antibody treatment for MS is available at this time?
Natalizumab (Tysabri®) is an FDA approved monoclonal antibody treatment targeting T-cells (CD25+ T-cells) for use in patients with relapsing-remitting MS or secondary progressive MS with continued relapses. Efficacy was demonstrated in two multi-center trials where the risk of progressive multi-focal leukoencephalopathy (PML) was first discovered. Tysabri was pulled from the market and later reintroduced in June 2006 in the US under the TOUCH™ program. Since that time 31 patients have developed PML and 5 of those patients have died.
The TOUCH™ program for natalizumab requires multiple provider and facility certifications and persistent monitoring of patients throughout their use of this treatment. Logistics of handling the medication and the cost are substantial with reported reported reimbursements ranging from $2400 to $12,000 per infusion (according to MSers who shared with me this information last year). The medication is administered every four weeks by intravenous infusion (IV) at which time patients are screened for problems and must sign a document acknowledging the risks of therapy prior to receiving the drug. In the US, you can only receive Tysabri if you are enrolled in the TOUCH™ program.
What are some monoclonal antibody treatments in development for MS?
At present, several additional monoclonal antibodies are being studied as investigational treatments for MS. They are not currently available for routine use in the treatment of MS.
Rituximab (Rituxan®) is a monoclonal antibody directed at B-cells (CD20+ B-cells) and has been reported to be effective in the treatment of relapsing-remitting MS. Studies in primary progressive MS did not produce statistically significant results however. This drug is FDA approved for treatment of rheumatoid arthritis and non-Hodgkin’s lymphoma. (Read more about Rituxan in Rituximab Infusion: My First Experience)
[Note: I believe that ocrelizumab and ofatumumab which target CD20+ B-cells, humanized and fully human monoclonal antibodies respectively, already have replaced rituximab in active MS studies. See listing in clinicaltrials.gov.]
Alemtuzumab (Campath®) is another monoclonal antibody directed at lymphocytes (CD52+ B-cells) which is under investigation for treatment in MS. Campath was found to be more effective than Rebif in early relapsing-remitting MS. Both rituximab and alemtuzumab are associated with longer-term immunosuppression (6 to 12 months). Serious immunological and infectious complications have occurred with both these monoclonal antibody therapies.
Daclizumab (Zenapax®) is FDA approved for the treatment of kidney transplant rejection. Zenapax is a humanized monoclonal therapy which targets CD25+ T-cells and blocks IL-2. It is sometimes used off-label by people with relapsing-remitting and worsening MS. Most often these patients have failed several other treatments. Efficacy has been demonstrated in off-label experience, two small phase II studies, and a larger multi-center phase II study. Currently, a longer duration multi-center phase II trial is in progress in Europe. Rash, fever, and occasional overgrowth of lymph nodes have been observed in people on long-term therapy with this drug.
Who should consider monoclonal antibody treatment?
The immunomodulatory treatments that are FDA approved for MS include glatiramer acetate (Copaxone®) and interferons (Betaseron®, Avonex®, and Rebif®). People with MS whose disease is well-controlled by immunomodulatory treatment (or disease-modifying drugs) should not need to advance to monoclonal antibody treatment. However, if a person continues to have significant disease activity, resulting in relapses or acute changes on MRI while on a disease-modifying drug, then he or she may be a good candidate for monoclonal antibody treatment.
The decision to treat, not to treat, or how to treat your multiple sclerosis is a very personal one. Always discuss your available options with your neurologist and learn as much as you can about those options. In the near future, oral MS drugs will be hitting the market and we will have additional options. That will certainly be exciting news when it happens.
Monoclonal antibodies in MS: Mechanisms of action. Bielekova B, and Becker BL. Neurology 2010;74:S31-S40
Monoclonal Antibodies: A New Way to Treat MS. Denise Campagnolo, MD, MS Director, Clinical MS Research, Barrow Neurological Institute, Phoenix, Arizona. United Spinal’s MS Scene (2008).
Monoclonal Antibody Treatment in MS. John Rose, MD, Chief of Neurology, VA Medical Center, Salt Lake City, UT. Multiple Sclerosis Center of Excellence website.
The Immune System - In More Detail. The Nobel Foundation website.
For More (Technical) Information:
Monoclonal Antibodies in Multiple Sclerosis Treatment: Current and Future Steps. Helliwell CL, Coles AJ. Therapeutic Advances in Neurological Disorders 2009;2(4):195-203.
Treating Multiple Sclerosis With Monoclonal Antibodies. Buttman M, Rieckmann P, et al. Expert Review Neurotherapeutics 2008;8(3):433-455.
Recent developments in multiple sclerosis therapeutics. Spain RI, Cameron MH and Bourdette D. BMC Medicine 2009;7:74 (regarding alemtuzumab)
Effect of Anti-CD25 Antibody Daclizumab in the Inhibition of Inflammation and Stabilization of Disease Progression in Multiple Sclerosis. Bielekova B, Howard T, Packer AN, et al. Archives of Neurology 2009; 66(4):483-489.