Real-world propensity score comparison of treatment effectiveness of peginterferon beta-1a vs. subcutaneous interferon beta-1a, glatiramer acetate, and teriflunomide in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple disease-modifying therapies (DMTs) have been approved by the U.S. Food & Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In separately conducted clinical trials, peginterferon beta-1a, subcutaneous interferon beta-1a (SC IFN beta-1a), glatiramer acetate (GA), and teriflunomide have demonstrated efficacy for reducing relapses. No head-to-head phase III clinical trials have directly compared the treatment efficacy of peginterferon beta-1a with these other DMTs. OBJECTIVES: A propensity score-based comparison was conducted of the treatment effectiveness of peginterferon beta-1a vs. SC IFN beta-1a, GA, and teriflunomide among patients with RRMS identified from a large U.S. administrative healthcare claims database. METHODS: Adult patients (18-65 years of age) who had ≥1 claim for an MS diagnosis between November 2013 and June 2017 and ≥1 claim for peginterferon beta-1a, SC IFN beta-1a, GA, or teriflunomide between November 1, 2014, and March 31, 2017 were identified from the IBM® MarketScan® Commercial database. The index date was the first claim of a patient's DMT initiated. Only patients who had ≥12 months of insurance enrollment pre-index (baseline period) and ≥90 days post-index (variable length follow-up period) were included. Patients were grouped into cohorts according to the index DMT. Patient demographics and clinical characteristics were evaluated. Propensity score matching (PSM) was separately conducted for pairwise comparisons of treatment effectiveness between peginterferon beta-1a and the other DMT cohorts. During the post-index follow-up period, annualized relapse rate (ARR; relapse defined as hospitalization or outpatient visit with subsequent treatment), annualized number and length of inpatient stays, and the number of claims for durable medical equipment were evaluated. RESULTS: With PSM, there were 325 patients (mean age: 46.0 years) in the peginterferon beta-1a cohort compared to 967 (mean age: 46.9 years) in the SC IFN beta-1a cohort; likewise there were 564 patients (mean age: 47.4 years) in the peginterferon beta-1a and 1688 (mean age: 47.6 years) in the GA cohort; and finally there were 584 patients (mean age: 49.1 years) in the peginterferon beta-1a cohort and 1742 (mean age: 49.0 years) in the teriflunomide cohort. During the post-index follow-up period, the ARR did not significantly differ between the peginterferon beta-1a and SC IFN beta-1a cohorts; the ARR was lower among patients treated with peginterferon beta-1a than among those treated with GA (Least squares mean [LSM] estimate: 0.25 vs. 0.31; LSM ratio: 0.809; P=0.027) or teriflunomide (LSM estimate: 0.26 vs. 0.37; LSM ratio: 0.704; P<0.001). The annualized mean number and length of inpatient stays and the mean number of claims for durable medical equipment during the post-index follow-up did not differ between the matched peginterferon beta-1a and GA cohorts nor the peginterferon beta-1a and teriflunomide cohorts. CONCLUSION: In this real-world comparative analysis of patients with similar patient characteristics, treatment with peginterferon beta-1a was associated with lower ARRs than treatment with either GA or teriflunomide; ARRs did not differ among patients treated with SC IFN beta-1a. Also, all other measured secondary outcomes did not differ between study cohorts. These real-world data may help support decision-making in the treatment of patients with RRMS.

Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol.

BACKGROUND: Ocrelizumab is a monoclonal antibody directed against CD20+ B cells that is approved for MS. The most common side effect is infusion-associated reactions (IARs). This study examines whether a modified premedication protocol reduces incidence of IARs and further examines predictors of IARs. METHODS: Patients took cetirizine 10 mg, ranitidine 75 mg, and increased hydration the night before the ocrelizumab infusion. This regimen was repeated the next day prior to arrival. Just prior to the infusion, patients were pretreated with IV diphenhydramine 50 mg, IV methylprednisolone 125 mg, and oral acetaminophen 650 mg. Rates of IARs with this modified protocol were compared to patients who had received only pretreatment medications. RESULTS: 207 patients received ocrelizumab. With the modified premedication protocol, we found significant decreased odds of IARs (OR 0.40, p = 0.024, 95% CI (0.18, 0.88). Among the baseline characteristics, there was a significant reduction of IARs with increasing age (OR 0.94, p = 0.001) and male sex (OR 0.34, p = 0.034). Body mass index (BMI) increased the odds of IARs (OR 1.07, p = 0.029). Race and smoking status did not affect IARs. CONCLUSION: The modified premedication protocol described herein significantly decreases rates of IARs by 60% and suggests that the additional premedication regimen is beneficial. Age and male sex are protective for IARs while BMI is a risk factor for IARs.

Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment.

BACKGROUND: Brain volume loss is an important surrogate marker for assessing disability in MS; however, contribution of gray and white matter to the whole brain volume loss needs further examination in the context of specific MS treatment. OBJECTIVES: To examine whole and segmented gray, white, thalamic, and corpus callosum volume loss in stable patients receiving natalizumab for 2-5 years. METHODS: This was a retrospective study of 20 patients undergoing treatment with natalizumab for 24-68 months. Whole brain volume loss was determined with SIENA. Gray and white matter segmentation was done using FAST. Thalamic and corpus callosum volumes were determined using Freesurfer. T1 relaxation values of chronic hypointense lesions (black holes) were determined using a quantitative, in-house developed method to assess lesion evolution. RESULTS: Over a mean of 36.6 months, median percent brain volume change (PBVC) was -2.0% (IQR 0.99-2.99). There was decline in gray (p = 0.001) but not white matter (p = 0.6), and thalamic (p = 0.01) but not corpus callosum volume (p = 0.09). Gray matter loss correlated with PBVC (Spearman's r = 0.64, p = 0.003) but not white matter (Spearman's r = 0.42, p = 0.07). Age significantly influenced whole brain volume loss (p = 0.010, multivariate regression), but disease duration and baseline T2 lesion volume did not. There was no change in T1 relaxation values of lesions or T2 lesion volume over time. All patients remained clinically stable. CONCLUSIONS: These results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment.