Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years

Abstract

Background: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit-risk profile.

Objective: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.5 years.

Methods: Patients completing ASCLEPIOS I/II (phase 3), APLIOS, or APOLITOS (phase 2) trials could enter ALITHIOS, a phase 3b, open-label, long-term safety study. We analyzed cumulative data of continuous ofatumumab treatment and of patients newly switched from teriflunomide.

Results: The safety population had 1969 patients: 1292 continuously treated with ofatumumab (median time-at-risk 35.5 months, 3253 patient-years) and 677 newly switched (median time-at-risk 18.3 months, 986 patient-years). A total of 1650 patients (83.8%) had ⩾1 adverse events and 191 (9.7%) had ⩾1 serious adverse events. No opportunistic infections or progressive multifocal leukoencephalopathy events were identified; the risk of malignancies was low. Mean serum immunoglobulin (Ig) G levels remained stable. Mean IgM levels decreased but remained above the lower limit of normal in most. Serious infection incidence was low; decreased Ig levels were not associated with serious infections.

Conclusion: In patients with up to 3.5 years' exposure, ofatumumab was well tolerated, with no new safety risks identified. These findings, with its established effectiveness, support a favorable benefit-risk profile of ofatumumab in RMS.

Keywords: Ofatumumab; antibodies; monoclonal; multiple sclerosis; relapsing multiple sclerosis; safety.

Figure 1.

Schematic summary of the patient flow in the analysis groups. APOLITOS had two phases: a core phase of 0–24 weeks and an extension phase of 24–48 weeks.

Figure 2.

Injection-related systemic reactions by injection number in the newly switched group (first five injections).

Figure 3.

Serum immunoglobulin levels from baseline up to week 168 in the continuous and newly switched groups (safety analysis set): (a) IgG levels and (b) IgM levels. R1: The first patient with first treatment-emergent assessment in ofatumumab period after switching to ofatumumab (72 weeks); R2: The last patient with last treatment-emergent assessment in teriflunomide period before switching to ofatumumab (120 weeks); BL: baseline; Ig: immunoglobin; LLN: lower limit of normal; SE: standard error.

Figure 4.

Serum immunoglobulin levels up to week 168 in the continuous ofatumumab group, by baseline quartile value (safety analysis set): (a) IgG levels and (b) IgM levels. IgG quartiles (Q): Q1, <8.57 g/L; Q2, ⩾8.57 and <10.07 g/L; Q3, ⩾10.07 and <11.51 g/L; Q4, ⩾11.51 g/L. IgM quartiles (Q): Q1, <0.81 g/L; Q2, ⩾0.81 and <1.14 g/L; Q3, ⩾1.14 and <1.57 g/L; Q4, ⩾1.57 g/L. BL, baseline; Ig: immunoglobin; SE: standard error.