No association between Ig levels and infection in ofatumumab-treated patients with relapsing MS

Multiple sclerosis (MS) patients are at an increased risk of infections compared with the general population. A recent analysis of the phase 3 ASCLEPIOS I/ASCLEPIOS II trials showed no association between a decrease in serum immunoglobulin (Ig) levels and the incidence of infections in ofatumumab-treated patients with relapsing MS.

Igs play a major role in immunoprotection. In MS patients receiving disease-modifying therapies, particularly B-cell-depleting therapies, serum IgM and IgG levels below the lower limit of normal (LLN) have been associated with an increased risk of infections. Igs have also been considered as a biomarker for assessment of infection risk in MS patients.

In the phase 3 ASCLEPIOS I/II trials, ofatumumab, a fully human anti-CD20 monoclonal antibody with a monthly 20 mg subcutaneous dosing regimen, demonstrated superior efficacy versus teriflunomide 14 mg oral once daily, and a manageable safety profile in patients with relapsing MS [1]. Now, in a study presented by Prof. Heinz Wiendl (University of Muenster, Germany), it was shown that average serum IgG and IgM levels remained well within the reference ranges over time in both treatment groups [2]. In a few patients, a reduction in the mean serum IgM levels from baseline was observed over time, but these levels remained well above the LLN. There was no decrease in mean IgG levels from baseline over time.

In addition, the current analysis showed no association between a decrease in Ig levels and the incidence of infections in both ofatumumab- and teriflunomide-treated patients. A total of 31.1% and 29.0% of patients, respectively, experienced at least 1 infection within 1 month prior and until 1 month after the reduction in Ig levels below the LLN. Most infections reported were non-serious in nature and were mild to moderate in severity. Most cases resolved while patients were continuing treatment.

The authors concluded that assessing Ig levels prior to and during initiation of anti-CD20 therapy is important, but additional long-term studies are needed to elucidate the frequency and implications of low Ig levels at baseline and during treatment.

1. Hauser SL, et al. N Engl J Med. 2020;383:546–57.
2. Wiendl H, et al. Serum Immunoglobulin Levels and Infections in Relapsing Multiple Sclerosis. ECF 28^th Annual Meeting. Abstract 33.

Posted on 16 December 202022 February 2024