Conference Coverage

Alemtuzumab provides greater reductions in serum NfL than interferon beta-1a



Alemtuzumab is more effective than interferon beta-1a at reducing serum levels of neurofilament light chain (NfL) in treatment-naive patients with relapsing-remitting multiple sclerosis (MS), according to an analysis presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. This finding is consistent with the superior clinical efficacy of alemtuzumab, compared with interferon beta-1a, seen in clinical trials, said the researchers. The clinical implications of alemtuzumab’s reduction of NfL levels remain to be clarified.

The CARE-MS I trial indicated that alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in treatment-naive patients with relapsing-remitting MS. Serum NfL level may indicate response to disease-modifying therapy.

Evis Havari, MSc, laboratory head of neuroimmunology immunomodulation at Sanofi in Framingham, Mass., and colleagues analyzed CARE-MS I data to determine the effect of alemtuzumab and subcutaneous interferon beta-1a on serum NfL over 2 years. The investigators also sought to compare participants’ serum NfL levels with the age-dependent median serum NfL levels in healthy controls, based on the approach described by Disanto et al. (Ann Neurol. 2017;81[6]:857-70).

In CARE-MS I, the investigators measured serum NfL with a single-molecule array. They used Generalized Additive Models of Location, Scale, and Shape to model serum NfL distribution in healthy controls and its association with age. They also derived age-dependent percentiles of serum NfL. CARE-MS I patients received 44 mcg of subcutaneous interferon beta-1a 3 times per week or 12 mg/day of alemtuzumab (a 5-day course at baseline and a 3-day course at 1 year). To obtain an age-independent measure of serum NfL, the researchers dichotomized samples into levels above or below the median. They used repeated logistic regression to estimate odds ratios (ORs).

The age range of participants in CARE-MS I was 18-53 years. Mean Expanded Disability Status Scale score was 2.0. In all, 354 participants received alemtuzumab, and 157 received interferon beta-1a.

Median serum NfL levels for healthy controls ranged from 12.0 pg/mL at 18 years of age to 27.1 pg/mL at 53 years. Median serum NfL levels were similar between the alemtuzumab and interferon beta-1a groups at baseline (31.7 pg/mL vs. 31.4 pg/mL). At 6 months after treatment, median serum NfL levels were significantly lower with alemtuzumab than with interferon beta-1a (17.2 pg/mL vs. 21.4 pg/mL). These levels remained significantly lower at month 24 in the alemtuzumab group (13.2 pg/mL vs. 18.7 pg/mL).

Significantly fewer patients in the alemtuzumab group had serum NfL levels higher than the age-dependent median in healthy controls at each post baseline time point, compared with the interferon beta-1a group (month 6: 46% vs. 65%; month 12: 38% vs. 53%; month 18: 31% vs. 44%; month 24: 28% vs. 53%). The odds for achieving serum NfL levels less than or equal to median levels for healthy controls were significantly greater for alemtuzumab than interferon beta-1a at month 6 (OR, 2.34), month 12 (OR, 1.81), month 18 (OR, 1.72), and month 24 (OR, 2.85).

Sanofi and Bayer HealthCare Pharmaceuticals supported the study. Several of the investigators are employees of Sanofi.

SOURCE: Havari E et al. CMSC 2019. Abstract NIB01.

Next Article: