To determine serum immunoglobulin (Ig) levels and investigate associations between IgG/IgM levels and infection risk in ofatumumab-treated patients.

Ofatumumab, the first fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide in RMS patients in Phase 3 ASCLEPIOS I/II trials. A decline in serum Ig levels was observed with other anti-CD20 therapies.

In the ASCLEPIOS trials, patients received subcutaneous ofatumumab 20mg on Days 1, 7, and 14, Week 4, and every 4 weeks thereafter or once-daily oral teriflunomide 14mg for up to 30 months (average follow-up duration: 18 months). Serum IgG/IgM levels were monitored at baseline, Weeks 4 and 12, and every 12 weeks thereafter (ofatumumab, n=946; teriflunomide, n=936). A notable decline in IgG/IgM levels was defined as 50% of the lower limit of normal (LLN) at any time (IgG, 3.5 g/L; IgM, 0.2 g/L). Outcomes included the proportion of patients with IgG/IgM levels <50% LLN, and association between low IgG/IgM levels and infection incidence.

At Week 120, no patients reached IgG levels <50% LLN with ofatumumab (median IgG [g/L]: ASCLEPIOS I and II, 10.57 and 9.57, respectively) or teriflunomide (10.01 and 9.65). The proportion of patients who reached IgM levels <50% LLN was 2.1% (n=20/944) with ofatumumab (median IgM [g/L]: 0.91 and 0.59) and 0.6% (n=6/933) with teriflunomide (median IgM [g/L]: 0.84 and 0.92) at Week 120. Of these patients, five experienced infections with ofatumumab, mostly non-serious (Grade 1/2 in severity), except one Grade 3 recurrent urinary tract infection. All infections resolved at time of last follow-up. One patient on teriflunomide who experienced nasopharyngitis had not recovered at time of last follow-up.

A reduction in serum IgG levels <50% LLN was not observed with either treatment. IgM levels showed reductions with both ofatumumab and teriflunomide treatments; there was no apparent association with treatment and increased rate of serious/non-serious infections.