Ofatumumab vs. Teriflunomide: Comparing Two Multiple Sclerosis Treatments

Table of Contents

• Background: Understanding MS Treatment Options
• Study Methods: How the Research Was Conducted
• Patient Characteristics: Who Participated in the Trials
• Key Findings: Detailed Results from Both Trials
• Safety Profile: Side Effects and Adverse Events
• Conclusions: What the Research Means for Patients
• Study Limitations: What the Research Couldn't Show
• Patient Recommendations: Considering Your Options
• Source Information

Background: Understanding MS Treatment Options

Multiple sclerosis is a complex neurological condition where the immune system mistakenly attacks the protective covering of nerve fibers. Research has shown that B cells, a type of immune cell, play a significant role in this process. Ofatumumab is a subcutaneous (under-the-skin) medication that specifically targets and depletes B cells. It's a fully human antibody that binds to CD20 receptors on B cells differently than other similar medications.

Teriflunomide, taken orally once daily, works through a different mechanism by inhibiting pyrimidine synthesis, which reduces activation of both T cells and B cells. While both medications are approved for treating relapsing multiple sclerosis, their relative effectiveness hadn't been directly compared in large clinical trials until this research.

Previous studies suggested that teriflunomide has similar effectiveness to older injectable medications like interferons and glatiramer acetate, but might be less effective than newer oral treatments and monoclonal antibodies. This study aimed to provide clear, direct comparison data to help patients and doctors make more informed treatment decisions.

Study Methods: How the Research Was Conducted

The ASCLEPIOS I and II trials were two identical phase 3 clinical trials conducted simultaneously at multiple medical centers worldwide. These were double-blind, double-dummy studies, meaning neither patients nor researchers knew who was receiving which active medication. Patients received either both active medications or both placebos to maintain the blind.

Patients were randomly assigned to receive either:

1. Subcutaneous ofatumumab (20 mg every 4 weeks after loading doses on days 1, 7, and 14) plus oral placebo
2. Oral teriflunomide (14 mg daily) plus subcutaneous placebo injections

The treatment period lasted up to 30 months, with a median follow-up of 1.6 years. Patients learned to self-administer the subcutaneous injections after the first month under medical supervision. The trials were designed to detect a 40% difference in annual relapse rates between the two treatments with over 90% statistical power.

Researchers measured multiple outcomes including:

• Annualized relapse rate (number of confirmed MS relapses per year)
• Disability progression confirmed at 3 and 6 months
• Disability improvement confirmed at 6 months
• MRI measures of brain lesions and volume changes
• Blood levels of neurofilament light chain (a biomarker of nerve damage)
• Safety and side effect profiles

Patient Characteristics: Who Participated in the Trials

The trials included 1,882 patients total - 946 assigned to ofatumumab and 936 to teriflunomide. Participants were between 18-55 years old with relapsing forms of multiple sclerosis, including both relapsing-remitting MS and secondary progressive MS with ongoing disease activity.

Key patient characteristics at the start of the trials:

• Average age: 37.8-38.9 years across treatment groups
• Approximately 68% were women
• 94% had relapsing-remitting MS, 6% had secondary progressive MS with activity
• Average time since symptom onset: 8.2-8.4 years
• Average time since diagnosis: 5.5-5.8 years
• Approximately 40% had not received previous disease-modifying therapy
• Average Expanded Disability Status Scale (EDSS) score: 2.86-2.97 (moderate disability)

Patients had experienced an average of 1.2-1.3 relapses in the year before joining the trial. About 60% had no gadolinium-enhancing lesions on their baseline MRI scans, indicating varying levels of disease activity among participants.

Key Findings: Detailed Results from Both Trials

The results demonstrated consistently superior outcomes for ofatumumab across both trials and multiple measurement types. The primary endpoint, annualized relapse rate, showed dramatic differences between the two treatments.

In ASCLEPIOS I Trial:

• Ofatumumab group: 0.11 relapses per year
• Teriflunomide group: 0.22 relapses per year
• Difference: -0.11 (95% CI: -0.16 to -0.06)
• Statistical significance: P<0.001 (highly significant)

In ASCLEPIOS II Trial:

• Ofatumumab group: 0.10 relapses per year
• Teriflunomide group: 0.25 relapses per year
• Difference: -0.15 (95% CI: -0.20 to -0.09)
• Statistical significance: P<0.001 (highly significant)

When the data from both trials were combined, the disability outcomes also favored ofatumumab:

• Disability worsening confirmed at 3 months: 10.9% with ofatumumab vs. 15.0% with teriflunomide (hazard ratio 0.66, P=0.002)
• Disability worsening confirmed at 6 months: 8.1% with ofatumumab vs. 12.0% with teriflunomide (hazard ratio 0.68, P=0.01)
• Disability improvement confirmed at 6 months: 11.0% with ofatumumab vs. 8.1% with teriflunomide (hazard ratio 1.35, P=0.09)

MRI results showed substantial benefits for ofatumumab:

• Number of gadolinium-enhancing lesions per scan: 0.03-0.05 with ofatumumab vs. 0.24-0.51 with teriflunomide (rate ratios 0.10-0.11, P<0.001)
• Annual rate of new or enlarging T2 lesions: 0.72-1.41 with ofatumumab vs. 4.00-5.01 with teriflunomide (rate ratios 0.18-0.28, P<0.001)
• Serum neurofilament light chain levels (a biomarker of nerve damage) were significantly lower with ofatumumab at month 3 and beyond
• Brain volume changes showed no significant difference between treatments

Safety Profile: Side Effects and Adverse Events

Both treatments demonstrated generally favorable safety profiles, though with some differences in specific side effects. The most notable difference was in injection-related reactions, which were more common with ofatumumab.

Key safety findings:

• Injection-related reactions: 20.2% with ofatumumab vs. 15.0% with teriflunomide (placebo injections)
• Serious infections: 2.5% with ofatumumab vs. 1.8% with teriflunomide
• No unexpected safety signals emerged for either treatment
• The safety profile was consistent with what was previously known about these medications

The similar rates of serious infections between the two treatments is particularly noteworthy, as B-cell depleting therapies like ofatumumab might be expected to carry higher infection risks. The fact that infection rates were comparable suggests that ofatumumab's targeted mechanism provides efficacy without excessively compromising infection-fighting capability.

Conclusions: What the Research Means for Patients

This head-to-head comparison provides strong evidence that ofatumumab is more effective than teriflunomide across multiple important measures of multiple sclerosis disease activity. The approximately 50% reduction in annual relapse rates represents a clinically meaningful difference that could significantly impact patients' quality of life.

The disability outcomes are particularly important, as preventing long-term disability accumulation is a primary goal of MS treatment. The 32-34% reduction in risk of disability progression with ofatumumab suggests this treatment may provide better long-term protection against permanent neurological damage.

The MRI results provide biological evidence supporting the clinical findings, showing substantially reduced inflammatory activity and lesion formation in the ofatumumab group. The reduction in neurofilament light chain levels further supports that ofatumumab more effectively reduces the underlying nerve damage process in MS.

Study Limitations: What the Research Couldn't Show

While these trials provide valuable comparative data, several limitations should be considered. The follow-up period of approximately 1.6 years is relatively short for a chronic condition like MS that evolves over decades. Longer-term data would be needed to understand how these treatments compare over extended periods.

The trials excluded patients with certain comorbidities and those who had received specific previous treatments, so the results may not fully apply to all MS patients in clinical practice. Additionally, the study population was primarily patients with relapsing-remitting MS, so the results may be less applicable to those with progressive forms without relapse activity.

The double-dummy design meant all patients received both injections and pills, which might affect how these results translate to real-world settings where patients typically receive only one formulation. Patient preferences for injection versus oral therapy weren't assessed in this study.

Patient Recommendations: Considering Your Options

Based on these findings, patients and clinicians should consider several factors when choosing between these treatments:

1. Efficacy priorities: If maximizing relapse reduction and disability protection is the primary goal, ofatumumab demonstrated superior effectiveness
2. Administration preferences: Ofatumumab requires monthly subcutaneous injections after initial loading doses, while teriflunomide is a daily oral medication
3. Side effect profile: Ofatumumab had higher rates of injection reactions, while both had similar infection risks
4. Individual risk factors: Personal medical history and specific concerns should guide shared decision-making with your neurologist
5. Insurance coverage: Practical considerations like insurance approval and out-of-pocket costs may influence treatment choices

These results provide the highest quality evidence available for comparing these two treatment approaches. Patients currently taking teriflunomide who continue to experience disease activity might discuss with their doctors whether switching to ofatumumab or another higher-efficacy therapy could provide better disease control.

Source Information

Original Article Title: Ofatumumab versus Teriflunomide in Multiple Sclerosis

Authors: S.L. Hauser, A. Bar-Or, J.A. Cohen, G. Comi, J. Correale, P.K. Coyle, A.H. Cross, J. de Seze, D. Leppert, X. Montalban, K. Selmaj, H. Wiendl, C. Kerloeguen, R. Willi, B. Li, A. Kakarieka, D. Tomic, A. Goodyear, R. Pingili, D.A. Häring, K. Ramanathan, M. Merschhemke, and L. Kappos, for the ASCLEPIOS I and ASCLEPIOS II Trial Groups

Publication: New England Journal of Medicine 2020;383:546-57

DOI: 10.1056/NEJMoa1917246

This patient-friendly article is based on peer-reviewed research from a major medical journal. It maintains all original data and findings while making the information accessible to patients and caregivers.