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ARTIOS

Efficacy and safety of ofatumumab in participants with relapsing multiple sclerosis and breakthrough disease on oral fingolimod or fumarates: results from the ARTIOS study

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Year of Publication: 2026

Authors: Bove R, Langdon D, Maciejowski M, ..., Derfuss T

Journal: Journal of Neurology

Citation: J Neurol 2026;273(7). DOI: 10.1007/s00415-026-13960-5 (PMID: 42371147; PMCID: PMC13315151; NCT04353492)

Link: https://doi.org/10.1007/s00415-026-13960-5

Bottom Line

In 562 adults with RMS and breakthrough disease on fingolimod or fumarates, switching to subcutaneous ofatumumab produced a low annualized relapse rate (0.06), near-complete suppression of MRI activity, high NEDA-3 rates (90.9% in Year 2), and few disability worsening events (7.3%), with a safety profile consistent with prior ofatumumab studies.

        Major Points
        Primary endpoint met: adjusted ARR 0.06 over 96 weeks (95% CI 0.05-0.08; p<0.0001), with Year 1 ARR 0.10 falling to 0.02 in Year 2
NEDA-3 achieved by 90.9% of participants in Year 2 despite the fingolimod subgroup having more advanced baseline disease
Gd+ T1 lesions reduced by 98.1% at Week 96; neT2 lesions dropped from 1.95 (Week 24) to 0.07 (Week 96)
Only 7.3% experienced 6-month confirmed disability worsening
TEAEs 90.6% (mostly mild-moderate), serious TEAEs 5.9%, treatment discontinuation for TEAE 0.9%, no deaths
Systemic IRRs common (53.4%) but concentrated after the first injection (45.6%) and none led to discontinuation
Mean IgG remained stable above LLN through Week 96; IgM decreased but stayed above LLN, with no severe infections attributed to low Ig
Post hoc analyses showed no clinically meaningful differences by washout duration; short (<30-day) washout may reduce rebound risk in fingolimod switchers

      

Design

Study Type: Phase 3b, open-label, single-arm, multicenter, noncomparative clinical trial

Randomization:

Blinding: Open-label

Enrollment Period: Registered April 20, 2020 (NCT04353492); initiated during first year of COVID-19 pandemic

Follow-up Duration: 96 weeks of treatment plus safety follow-up up to 6 months

Countries: Multinational — sites in USA, UK, Poland, Czechia, Germany, Spain, Switzerland (per author affiliations)

Sample Size: 562

Analysis: Full analysis set (all who received ≥1 dose) for efficacy; modified FAS for NEDA-3; Safety Set for AEs; ARR analyzed by negative binomial regression adjusted for prior DMT, prior-year relapses, baseline EDSS, T1 Gd+ lesions, and age

Inclusion Criteria

Adults aged 18-60 years
Relapsing MS (including active secondary progressive MS), diagnosed per 2017 revised McDonald criteria
EDSS score 0-4 at screening
Prior treatment with a maximum of 3 DMTs
Transitioning from fingolimod or fumarates administered for ≥6 months as last prior DMT
Breakthrough disease activity: ≥1 documented relapse in the past year, or ≥2 relapses in the past 2 years, or ≥1 Gd+ MRI lesion within the past year, or new/enlarging T2 lesions within the past year
Written informed consent

Exclusion Criteria

Age <18 or >60 years
EDSS >4 at screening
>3 prior DMTs
Last prior DMT other than fingolimod or fumarates
<6 months of prior fingolimod or fumarate therapy
Concurrent use of another DMT during the transition/screening period

Baseline Characteristics

Characteristic	Overall (N=562)	Fingolimod subgroup (n=181)	Fumarate subgroup (n=381)
Prior fingolimod	181 (32.2%)
Prior fumarates	381 (67.8%)
Mean ofatumumab exposure	91.8 weeks
Completed 96 weeks of treatment	523 (93.1%)
Discontinued study	39 (6.9%) — primarily participant decision (n=24)
MS disease duration since diagnosis		Longer than fumarate subgroup (p<0.05)
Relapses in past 12-24 months		Higher than fumarate subgroup (p<0.05)
Participants free of Gd+ T1 lesions at baseline		64.0%	76.2%
T2 lesion volume		Higher than fumarate subgroup
SDMT scores		Lower than fumarate subgroup
Number of prior DMTs		Higher than fumarate subgroup
Overall baseline disease severity			Less advanced than fingolimod subgroup

Arms

Field	Ofatumumab (single arm)
Intervention	Ofatumumab 20 mg subcutaneous via autoinjector — induction on Days 1, 7, and 14, then 20 mg every 4 weeks
Duration	96 weeks

Outcomes

Outcome	Type	Control	P-value
Annualized relapse rate (ARR) over 96 weeks	Primary		<0.0001
Adjusted rate of Gd+ T1 lesions per scan at baseline	Secondary	Value: 0.85 (95% CI 0.59-1.21)
Adjusted rate of Gd+ T1 lesions Week 24	Secondary		<0.0001
Adjusted rate of Gd+ T1 lesions Week 48	Secondary		<0.0001
Adjusted rate of Gd+ T1 lesions Week 96	Secondary		<0.0001
Adjusted number of neT2 lesions Week 24	Secondary	Value: 1.95 (95% CI 1.61-2.37)
Adjusted number of neT2 lesions Week 48	Secondary	Value: 0.16 (95% CI 0.11-0.23)
Adjusted number of neT2 lesions Week 96	Secondary	Value: 0.07 (95% CI 0.05-0.10)
NEDA-3 Year 1 (overall)	Secondary	Value: 51.8% (95% CI 47.6-56.0)
NEDA-3 Year 2 (overall)	Secondary	Value: 90.9% (95% CI 88.4-93.3)
NEDA-3 Year 1 (fingolimod)	Secondary	Value: 35.2% (95% CI 28.2-42.2)
NEDA-3 Year 2 (fingolimod)	Secondary	Value: 88.0% (95% CI 83.1-92.9)
NEDA-3 Year 1 (fumarates)	Secondary	Value: 59.8% (95% CI 54.8-64.8)
NEDA-3 Year 2 (fumarates)	Secondary	Value: 92.2% (95% CI 89.4-95.0)
6-month confirmed disability worsening (overall)	Secondary	Value: 40/562 (7.3%; 95% CI 5.4-9.9)
6mCDW fingolimod	Secondary	Value: 15/181 (8.5%; 95% CI 5.2-13.8)
6mCDW fumarates	Secondary	Value: 25/381 (6.8%; 95% CI 4.6-9.9)
6-month confirmed cognitive decline Year 1	Secondary	Value: 11.4%
6mCCD Year 2	Secondary	Value: 11.9%
T25FW, 9HPT, SDMT, LCVA	Secondary	Value: Stable; changes did not reach clinically meaningful thresholds
MSIS-29 physical and psychological	Secondary	Value: Stable — no functional decline
FSMC fatigue	Secondary	Value: No clinically meaningful change
TSQM (satisfaction, effectiveness, convenience)	Secondary	Value: Gradual improvement over the study
Serum NfL	Secondary	Value: Decreased from Week 24 and remained stable through Week 96
T2 lesion volume	Secondary	Value: Decreased from baseline
Any TEAE	Adverse	509/562 (90.6%) — 90.1% fingolimod vs 90.8% fumarates
Severity (mild or moderate, Grade 1-2)	Adverse	90.6% of TEAEs
Most common SOC (infections and infestations)	Adverse	69.8%
Systemic injection-related reactions (any)	Adverse	53.4% (grade 1: 35.6%; grade 2: 17.1%; grade 3: 0.5%; no grade 4 or serious IRRs)
Systemic IRRs after 1st injection	Adverse	45.6%
Cumulative systemic IRRs across subsequent injections	Adverse	7.6%
Local-site IRRs	Adverse	11.0% (all mild-moderate)
COVID-19	Adverse	37.0% (99.5% mild/moderate; 1 grade 3)
Nasopharyngitis	Adverse	17.1%
Headache	Adverse	16.4%
Serious TEAEs	Adverse	33/562 (5.9%) — 7.2% fingolimod, 5.2% fumarates
Recurring serious TEAEs (>1 participant, 0.4% each)	Adverse	Uterine leiomyoma, suicidal ideation, intervertebral disc protrusion
TEAEs leading to treatment interruption	Adverse	33 (5.9%) — largely COVID-19 (23; 4.1%)
Discontinuations due to TEAE	Adverse	5 (0.9%) — COVID-19 (1), MRI lesion initially suspected PML later confirmed as new MS lesion (1), cancers (3: adenocarcinoma, bladder cancer, medullary breast carcinoma)
Deaths	Adverse	0
Mean IgG through Week 96	Adverse	Stable, above lower limit of normal (5.65 g/L)
Mean IgM through Week 96	Adverse	Decreased from baseline but remained above LLN (0.4 g/L)
IgG <LLN post-baseline	Adverse	2.1% of participants
IgM <LLN post-baseline	Adverse	22.8% of participants (not associated with severe infection or discontinuation)

Subgroup Analysis

Efficacy consistent across prior fingolimod vs fumarates subgroups despite baseline severity differences. Post hoc analyses by washout duration showed no clinically meaningful differences; however, fingolimod switchers with a 30-60 day washout had a small, non-significant increase in Gd+ T1 and neT2 lesions vs those with <30-day washout, suggesting a shorter washout may reduce rebound risk. Safety consistent across washout durations.

Criticisms

Single-arm, open-label design without an active comparator limits definitive efficacy conclusions and cross-HET comparisons
Relatively short 96-week follow-up given the chronicity of MS
Regression to the mean is possible because enrollment was triggered by recent breakthrough disease activity
Few participants aged >55 years limits interpretation of NfL data by age
Study initiated during the first year of the COVID-19 pandemic, likely inflating infection-related TEAE rates
Lower premedication use than in ASCLEPIOS may have contributed to the higher rate of systemic IRRs
Investigator-flexible design (washout, symptom assessment timing) improves real-world relevance but introduces heterogeneity

Funding

Novartis (multiple author affiliations with Novartis Pharma AG (Basel), Novartis Pharmaceuticals UK (London), Novartis Pharmaceuticals Corporation (East Hanover, NJ), and Novartis Healthcare Private Limited (Hyderabad))

Based on: ARTIOS (Journal of Neurology, 2026)

Authors: Bove R, Langdon D, Maciejowski M, ..., Derfuss T

Citation: J Neurol 2026;273(7). DOI: 10.1007/s00415-026-13960-5 (PMID: 42371147; PMCID: PMC13315151; NCT04353492)

Content summarized and formatted by NeuroTrials.ai.

ARTIOS

(2026)

Objective

To evaluate the efficacy and safety of subcutaneous ofatumumab in adults with relapsing multiple sclerosis who switched from oral fingolimod or fumarates because of breakthrough disease activity.

Study Summary

• Adjusted annualized relapse rate was 0.06 (95% CI 0.05-0.08; p<0.0001) over 96 weeks, meeting the primary endpoint
• NEDA-3 was achieved by 90.9% of participants in Year 2 (88.0% fingolimod; 92.2% fumarates)
• Gd+ T1 lesions were reduced 93.7%, 97.3%, and 98.1% at Weeks 24, 48, and 96; neT2 lesions were nearly completely suppressed
• 6-month confirmed disability worsening occurred in only 7.3% of participants
• Safety profile consistent with prior ofatumumab trials: TEAEs 90.6% (mostly mild-moderate), serious TEAEs 5.9%, discontinuations 0.9%, no deaths

Intervention

Ofatumumab 20 mg subcutaneously (autoinjector) — induction doses on Days 1, 7, and 14, then 20 mg every 4 weeks

Inclusion Criteria

Adults 18-60 years with RMS (incl. active SPMS) by 2017 McDonald criteria, EDSS 0-4, ≤3 prior DMTs, on fingolimod or fumarates ≥6 months with breakthrough disease (≥1 relapse in past year, ≥2 relapses in past 2 years, or MRI activity)

Study Design

Arms: Single-arm, open-label ofatumumab (no comparator); subgroups by prior DMT (fingolimod vs fumarates)

Patients per Arm: 562 total — 181 prior fingolimod (32.2%), 381 prior fumarates (67.8%)

Outcome

• Primary: ARR 0.06 (95% CI 0.05-0.08; p<0.0001); fingolimod 0.09, fumarates 0.06; Year 1 0.10 → Year 2 0.02
• NEDA-3 Year 2: 90.9% overall (88.0% fingolimod; 92.2% fumarates)
• Gd+ T1 lesion reduction 98.1% at Week 96; neT2 lesions 1.95 → 0.07 (Weeks 24 → 96)
• 6mCDW 7.3% (8.5% fingolimod, 6.8% fumarates)
• TEAEs 90.6%; serious 5.9%; systemic IRRs 53.4% (45.6% after 1st injection, 7.6% cumulative thereafter); COVID-19 37.0%; 0 deaths; 0.9% discontinued due to TEAE

Clinical Question

In adults with relapsing multiple sclerosis and breakthrough disease on oral fingolimod or fumarates, does switching to subcutaneous ofatumumab reduce relapse and MRI activity while maintaining an acceptable safety profile?

Bottom Line

Major Points

Primary endpoint met: adjusted ARR 0.06 over 96 weeks (95% CI 0.05-0.08; p<0.0001), with Year 1 ARR 0.10 falling to 0.02 in Year 2
NEDA-3 achieved by 90.9% of participants in Year 2 despite the fingolimod subgroup having more advanced baseline disease
Gd+ T1 lesions reduced by 98.1% at Week 96; neT2 lesions dropped from 1.95 (Week 24) to 0.07 (Week 96)
Only 7.3% experienced 6-month confirmed disability worsening
TEAEs 90.6% (mostly mild-moderate), serious TEAEs 5.9%, treatment discontinuation for TEAE 0.9%, no deaths
Systemic IRRs common (53.4%) but concentrated after the first injection (45.6%) and none led to discontinuation
Mean IgG remained stable above LLN through Week 96; IgM decreased but stayed above LLN, with no severe infections attributed to low Ig
Post hoc analyses showed no clinically meaningful differences by washout duration; short (<30-day) washout may reduce rebound risk in fingolimod switchers

Study Design

Study Type: Phase 3b, open-label, single-arm, multicenter, noncomparative clinical trial
Randomization: No
Blinding: Open-label
Sample Size: 562
Follow-up: 96 weeks of treatment plus safety follow-up up to 6 months
Countries: Multinational — sites in USA, UK, Poland, Czechia, Germany, Spain, Switzerland (per author affiliations)

Primary Outcome

Definition: Annualized relapse rate (ARR) over 96 weeks

Control	Intervention	HR/OR	P-value
-	-	-	<0.0001

Limitations & Criticisms

Single-arm, open-label design without an active comparator limits definitive efficacy conclusions and cross-HET comparisons
Relatively short 96-week follow-up given the chronicity of MS
Regression to the mean is possible because enrollment was triggered by recent breakthrough disease activity
Few participants aged >55 years limits interpretation of NfL data by age
Study initiated during the first year of the COVID-19 pandemic, likely inflating infection-related TEAE rates
Lower premedication use than in ASCLEPIOS may have contributed to the higher rate of systemic IRRs
Investigator-flexible design (washout, symptom assessment timing) improves real-world relevance but introduces heterogeneity

Citation

J Neurol 2026;273(7). DOI: 10.1007/s00415-026-13960-5 (PMID: 42371147; PMCID: PMC13315151; NCT04353492)

View Original Publication →

ARTIOS

Efficacy and safety of ofatumumab in participants with relapsing multiple sclerosis and breakthrough disease on oral fingolimod or fumarates: results from the ARTIOS study

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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