Serum Immunoglobulin Levels and Infections in Relapsing Multiple Sclerosis

Abstract

Patients with MS are at an increased risk of infections compared with the general population. As immunoglobulins (Ig) play a major role in immunoprotection, serum IgM/IgG levels below the lower-limit-of-normal (<LLN) have been attributed to an increased risk of infections in MS patients receiving disease-modifying therapies, particularly B-cell-depleting therapies.

Objective:
Evaluate the association between serum IgM and IgG levels and risk of infections in relapsing MS (RMS). We report results from the Phase 3 ASCLEPIOS I/II trials, which led to US-FDA-approval of ofatumumab for RMS.

Methods:
Eligible patients with serum IgM/IgG≥LLN at screening were treated with monthly-subcutaneous ofatumumab 20mg (n=946) or once-daily oral teriflunomide 14mg (n=936) for up to 30 months(m). Serum IgM/IgG levels were monitored at baseline, Week (W)4, W12, and every 12 weeks thereafter. Proportion of patients with IgM/IgG<LLN and the association of IgM/IgG levels with incidence of infections occurred up to 1m prior and 1m after any decrease in IgM/IgG<LLN were analysed and compared with the IgM/IgG≥LLN group.

Results:
Mean IgM levels were reduced from baseline in both treatment groups, but remained well within the reference ranges. No decline in mean IgG levels was observed at the end-of-study; a transient reduction was observed until W36, which recovered thereafter in both treatment groups. Proportion of ofatumumab-treated patients with ≥1 infection (IgM/IgG<LLN vs IgM/IgG≥LLN) during a drop in IgM was 31.1% versus 51.5% and in IgG was 27.6% versus 50.6%. Common infections were nasopharyngitis, upper respiratory tract and urinary tract infections; majority were non-serious and mild-to-moderate in severity that were resolved while continuing ofatumumab treatment. No opportunistic infections were reported.

Conclusions:
There was no association between a decrease in immunoglobulin levels and incidence of infections observed in ofatumumab-treated RMS patients. More information, especially longer follow-up, is needed to understand the association of risk of infections with IgM/IgG<LLN.

Serum Immunoglobulin Levels and Infections in Relapsing Multiple Sclerosis

Heinz Wiendl1, Jérôme De Seze2, Anne H. Cross3, Kevin Winthrop4, Ayan Das Gupta5, Cecile Kerloeguen6, Ratnakar Pingili7, Roseanne Sullivan7, Krishnan Ramanathan6, Ludwig Kappos8

1University of Muenster, Muenster, Germany; 2University Hospital of Strasbourg, Strasbourg, France; 3Washington University School of Medicine, Saint Louis, MO, USA; 4Public Health and Preventive Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, Portland, OR, USA; 5Novartis Healthcare Pvt. Ltd., Hyderabad, India; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 8Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland

This study was funded by Novartis Pharma AG, Basel, Switzerland.
A detailed disclosure from each author will be included in the poster presentation.
Data have been previously presented at the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020, September 11-13, 2020.