Evidence map›Paper›PMID 22008873›Full record

Trial reportJournal of neurology2012

Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS.

Bianca Weinstock-Guttman, Steven L Galetta, Gavin Giovannoni, Eva Havrdova, Michael Hutchinson, Ludwig Kappos, Paul W O'Connor, J Theodore Phillips, Chris Polman, William H Stuart and 2 more

Abstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 6 pooled it
3.4field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 6 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Natalizumab for multiple sclerosis.The Cochrane database of systematic reviews · 2025
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pharmacological treatment for memory disorder in multiple sclerosis.The Cochrane database of systematic reviews · 2013
    Pooled it
  7. Trial
  8. Trial
  9. Article
  10. Article
  11. Review
  12. Article
  13. Disease-modifying drugs for multiple sclerosis and subsequent health service use.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022
    Article
  14. Observational
  15. Article
  16. Observational
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 12 institutions in 8 countries.

Bianca Weinstock-GuttmanJacobs Neurological Institute, Buffalo, NY 14203-1126, USA. bguttman@thejni.org
Steven L Galetta
Gavin Giovannoni
Eva Havrdova
Michael Hutchinson
Ludwig Kappos
Paul W O'Connor
J Theodore Phillips
Chris Polman
William H Stuart
Frances Lynn
Christophe Hotermans
Amsterdam UMC Location VUmc · NLBiogen (Switzerland) · CHBiogen (United Kingdom) · GBCharles University · CZHospital Base · CLJacobs Institute · USMultiple Sclerosis Center of Atlanta · USQueen Mary University of London · GBSt. Michael's Hospital · CASt. Vincent's University Hospital · IETexas Neurology · USUniversity of Pittsburgh Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Standard clinical endpoints in multiple sclerosis (MS) studies, such as disability progression defined by the expanded disability status scale (EDSS) and annualized relapse rate, may not fully reflect all aspects of therapeutic benefit experienced by patients. Pivotal studies showed that natalizumab is effective both as monotherapy (AFFIRM study) and in combination with interferon beta-1a (IFNβ-1a) (SENTINEL study) in patients with relapsing MS. We present AFFIRM and SENTINEL data demonstrating the efficacy of natalizumab on prespecified tertiary endpoints, including extent of confirmed change in EDSS score from baseline, time to sustained progression to EDSS milestone scores, hospitalizations, corticosteroid use, and time to confirmed progression of cognitive deficits. Natalizumab significantly reduced changes in EDSS scores (P < 0.001) and proportion of patients progressing to an EDSS score ≥4.0 (P < 0.001) and ≥6.0 (P = 0.002) compared with placebo. Natalizumab + IFNβ-1a significantly reduced changes in EDSS scores compared with placebo + IFNβ-1a (P = 0.011). Based on 0.5 standard deviation change in paced auditory serial addition test-3 score, natalizumab treatment reduced the risk of confirmed progression of cognitive deficits by 43% compared with placebo (HR 0.57 [95% CI 0.37, 0.89], P = 0.013); however, no significant difference between groups was seen in SENTINEL. Natalizumab, both as monotherapy and in combination with IFNβ-1a, significantly reduced the annualized rate of MS-related hospitalizations (by 64 and 61%, respectively) and the annualized rate of relapses severe enough to require steroid treatment (by 69 and 61%, respectively) compared with placebo and placebo + IFNβ-1a (P < 0.001). These analyses underline beneficial effects of natalizumab therapy in relapsing MS patients.

Indexed as

AdultAnalysis of VarianceAntibodies, Monoclonal, HumanizedCognition DisordersDisability EvaluationDose-Response Relationship, DrugDouble-Blind MethodFemaleHospitalizationHumansImmunologic FactorsInterferon-betaLongitudinal StudiesMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingAntibodies, Monoclonal, HumanizedImmunologic FactorsInterferon-betaNatalizumabSteroids

Identifiers

PMID22008873
OpenAlexW1981574714

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.