CONFERENCE UPDATE: AAN 2024

Long-term efficacy and safety of ofatumumab treatment for up to 6 years demonstrated in patients with RMS

NEUROLOGY
29 May 2024

Ofatumumab is a fully human monoclonal antibody (mAb) against CD20.1 Monthly subcutaneous injections of ofatumumab 20mg have previously been approved for the treatment of relapsing multiple sclerosis (RMS) in adult patients.1 Previously in the phase 3 ASCLEPIOS I/II trials, ofatumumab led to a greater reduction of the clinical and magnetic resonance imaging (MRI) disease activity in people with RMS (pwRMS) up to 30 months compared with teriflunomide.1 Additionally, results from the open-label extension (OLE) study, ALITHIOS, substantiated the sustained efficacy of ofatumumab in pwRMS for up to 5 years.1 In the captioned analysis, the longer-term safety and efficacy of ofatumumab treatment for up to 6 years in pwRMS were evaluated to further elucidate the benefit-risk profile of ofatumumab in pwRMS.1

The efficacy analyses included data from all participants (n=1,882) randomized to receive ofatumumab (n=946) or teriflunomide (n=936) in the ASCLEPIOS I/II trials.1 The safety analyses included data from all participants who received at least one dose of ofatumumab in the ASCLEPIOS I/II, APOLITOS, APLIOS or ALITHIOS trials (n=1,969).1 Participants treated with teriflunomide in ASCLEPIOS I/II were switched to ofatumumab (TER-OMB group), while those assigned ofatumumab in the initial trial continued to receive ofatumumab in the ALITHIOS OLE (OMB-OMB group).1

The efficacy outcomes assessed included the annualized relapse rate (ARR), mean number of gadolinium-enhancing (Gd+) T1 lesions per scan, number of new or enlarging T2 (neT2) lesions per year, 6-month confirmed disability worsening (6mCDW) and no evidence of disease activity (NEDA-3) which was defined by having none of the above outcomes.1 Safety outcomes included the overall safety profile, serious infections, malignancies and laboratory parameters (immunoglobulin [Ig] G and IgM levels), lymphocyte and neutrophil counts and malignancies.1

FINDINGS

Efficacy outcomes:
  • The efficacy outcomes included ARR, Gd+ T1 lesion per scan, neT2 lesion per year, 6mCDW and NEDA-31
  • A significant decline in ARR from the core period to the OLE period was observed in the OMB-OMB group (-49.9%; rate ratio [RR]=0.501; 95% CI: 0.399-0.630; p<0.001) and the TER-OMB group (-73.8%; RR=0.262; 95% CI: 0.214-0.320; p<0.001)1
  • A low ARR was seen throughout the ALITHIOS period across both OMB-OMB group (0.054; 95% CI: 0.041-0.071) and the TER-OMB group (0.060; 95% CI: 0.046-0.079)1
  • Switching from teriflunomide to ofatumumab led to a suppression of Gd+ T1 lesion activity by 97.7% (RR=0.023; 95% CI: 0.016-0.033; p<0.001) in the OLE period where the adjusted mean number of Gd+ lesions per scan reduced from 0.551 to 0.0131
  • There was over 89% reduction in the annualized mean rate of neT2 lesions from the core period to the OLE period in both TER-OMB group (-91.8%; RR=0.082; 95% CI: 0.069-0.098; p<0.001) and OMB-OMB group (-89.3%; RR=0.107; 95% CI: 0.085-0.135; p<0.001)1
  • At year 6, a similar proportion of patients in the TER-OMB group achieved NEDA-3 compared with those in the OMB-OMB group (odds ratio [OR]=1.12; 95% CI: 0.74-1.68; p=0.599), where over 90% of patients in both groups achieved NEDA-31

Safety:
  • No ofatumumab-associated increased risks of AEs, SAEs, serious infections and malignancies were found over 6 years1
  • No clinical association between the risk of serious infection and IgG or IgM levels was found despite the drop in IgM levels which remained above the lower limit of normal and stable levels of IgG1

 

“These results support the long-term, favorable benefit-risk profile of ofatumumab treatment (up to 6 years) and reinforce the benefit of early ofatumumab initiation in pwRMS”

Dr. Tuan Vu
College of Medicine,
University of South Florida Morsani,
Florida, United States

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