BACKGROUND:Bladder dysfunction is a common symptom of multiple sclerosis (MS). This study was designed to evaluate effects of natalizumab on bladder function in patients with relapsing-remitting MS.METHODS:The TRUST (EvaluaTion of Bladder Function in Relapsing-Remitting MUltiple Sclerosis Patients Treated with Natalizumab) study was an open-label, single-arm, two-center study. Natalizumab-naive MS patients with disabling bladder dysfunction and initiating natalizumab were enrolled and followed for 6 months. The primary endpoint was change in the Urogenital Distress Inventory short form (UDI-6) score from baseline. Change in Incontinence Impact Questionnaire short form (IIQ-7) score from baseline was a secondary endpoint.RESULTS:Thirty patients were enrolled. Mean baseline characteristics were age 49.9 years, Expanded Disability Status Scale score 4.6, number of relapses in previous year 2.4, UDI-6 score 10.4, and IIQ-7 score 12.3. Mean changes in UDI-6 and IIQ-7 scores were significantly improved from baseline beginning at week 4 and up to week 24; mean improvements at 24 weeks were 4.4 (P < .0001) and 4.9 (P = .0005) points, respectively. At week 24, 85.7% and 78.6% of patients demonstrated improvements from baseline in UDI-6 and IIQ-7 scores, respectively.CONCLUSIONS:Incontinence-related quality of life as measured by UDI-6 and IIQ-7 scores improved significantly during natalizumab treatment.

Currently approved disease-modifying therapies for multiple sclerosis (MS) are only partially effective. This study evaluated the efficacy and safety of combination therapy with intramuscular (IM) interferon beta (IFNβ)-1a (Avonex) in patients with disease that progressed despite treatment. A retrospective chart review of all patients from the MS Center of Atlanta, Georgia, was performed (N ≈1300). Eligible patients had a diagnosis of relapsing MS, were treated with IM IFNβ-1a for ≥12 months before initiation of combination therapy, and were on combination therapy for active disease. In addition, patient records must have contained data on relapses, Expanded Disability Status Scale (EDSS) scores, magnetic resonance imaging (MRI) scans, laboratory values, and adverse events. Patients were identified who had been treated with the following in addition to IM IFNβ-1a: pulse corticosteroids only (n = 25), pulse corticosteroids plus mycophenolate mofetil (n = 8), and pulse corticosteroids plus cyclophosphamide (n = 13). The annualized relapse rate was significantly reduced by all three treatments compared with monotherapy (all P ≤.01). For all three groups, no significant improvement was observed with combination therapy compared with monotherapy on evaluations of stable EDSS scores and MRI scans. Three serious adverse events were noted, with two considered related to study medication: one with mycophenolate mofetil (abnormal liver function test results resolved with discontinuation of drug) and one with cyclophosphamide (white blood cell count decrease resolved by withholding one dose). These data suggest that combination therapy is a viable option for the treatment of active MS.