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Multiple sclerosis (MS) is a disease of the CNS with a challenging clinical course characterized by heterogeneous symptoms related to inflammation and demyelination. Disease-modifying agents (DMAs) are used to treat the related neuronal degradation. Certain symptoms occur regularly, although with variable frequency, regardless of treatment with DMAs. Because there is no cure for MS at this time, symptom management is critically important to quality of life. Symptoms commonly seen are spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction. Other symptoms include depression, bowel dysfunction, paroxysmal symptoms, and weakness. The symptom management model that provides optimal results for patients with MS is a multimodal approach using effective communication, patient education, physical modalities and activities, occupational and other therapies, and pharmacologic interventions. Individualizing treatment for each patient involves gaining control of symptoms as early as possible to prevent cycles of symptoms from developing.

Objective: To evaluate the safety and tolerability of natalizumab when added to glatiramer acetate (GA) in patients with relapsing multiple sclerosis. The primary outcome assessed whether this combination would increase the rate of development of new active lesions on cranial MRI scans vs GA alone. Methods:This phase 2, randomized, double-blind, placebo-controlled study included patients aged 19 to 55 years who were treated with GA for at least 1 year before randomization and experienced at least one relapse during the previous year. Patients received IV natalizumab 300 mg (n ϭ 55) or placebo (n ϭ 55) once every 4 weeks plus GA 20 mg subcutaneously once daily for Յ20 weeks. Results:The mean rate of development of new active lesions was 0.03 with combination therapy vs 0.11 with GA alone (p ϭ 0.031). Combination therapy resulted in lower mean numbers of new gadolinium-enhancing lesions (0.6 vs 2.3 for GA alone, p ϭ 0.020) and new/newly enlarging T2-hyperintense lesions (0.5 vs 1.3, p ϭ 0.029). The incidence of infection and infusion reactions was similar in both groups; no hypersensitivity reactions were observed. One serious adverse event occurred with combination therapy (elective hip surgery). With the exception of an increase in anti-natalizumab antibodies with combination therapy, laboratory data were consistent with previous clinical studies of natalizumab alone. Conclusion:The combination of natalizumab and glatiramer acetate seemed safe and well tolerated during 6 months of therapy. Neurology Interferon ␤ (IFN␤) and glatiramer acetate (GA) are only partially effective for treatment of relapsing multiple sclerosis (MS); approximately two-thirds of patients continue to experience relapses on these therapies over 2 years.1-4 New focal inflammatory lesions in MS are believed to occur when activated T cells cross the blood-brain barrier and initiate a series of events leading to activation of endothelial cells, recruitment of additional lymphocytes and monocytes, release of proinflammatory cytokines, and subsequent demyelination and formation of MS plaques. 5The interaction of ␣ 4 ␤ 1 integrin on leukocytes with vascular cell adhesion molecule 1 on brain endothelial cells is a critical step in migration of leukocytes across the blood-brain barrier. [6][7][8] Natalizumab binds to the ␣ 4 subunit of ␣ 4 ␤ 1 integrin, thereby inhibiting leukocyte trafficking into the CNS (by blocking interactions with molecules including the CS-1 fragment of fibronectin and vascular cell adhesion molecule 1) and potentially altering cell-cell interactions and T-cell activation. [9][10][11]

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