Evidence map›Paper›PMID 28856176›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2017

α4-integrin receptor desaturation and disease activity return after natalizumab cessation.

Tobias Derfuss, John M Kovarik, Ludwig Kappos, Marina Savelieva, Richa Chhabra, Avinash Thakur, Ying Zhang, Heinz Wiendl, Davorka Tomic

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01499667 (A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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.

NCT01499667 phase3terminatednot on this map

A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)

TypeinterventionalSponsorNovartis PharmaceuticalsRan2011 to 2012Enrolled142ConditionsRelapsing Remitting Multiple Sclerosis (RRMS)ArmsFingolimod, Placebo
3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Natalizumab Rebound in Multiple Sclerosis.The Neurohospitalist · 2022
    Article
  9. Article
  10. Pharmacodynamics of natalizumab extended interval dosing in MS.Neurology(R) neuroimmunology & neuroinflammation · 2020
    Article
  11. Evolution of the EU Biosimilar Framework: Past and Future.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2019
    Review
  12. Article
  13. Article
  14. Article
  15. 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

9 authors.

Tobias DerfussNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
John M KovarikNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Ludwig KapposNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Marina SavelievaNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Richa ChhabraNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Avinash ThakurNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Ying ZhangNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Heinz WiendlNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.
Davorka TomicNeurological Clinic and Policlinic (T.D.), Departments of Medicine and Biomedicine, University Hospital Basel; Novartis Pharma AG (J.M.K., M.S., D.T.), Basel; Neurological Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Switzerland; Novartis Pharmaceuticals Corporation (Y.Z.), East Hanover, NJ; and Department of Neurology (H.W.), University of Münster, Germany; Novartis Healthcare Pvt. Ltd. (R.C.. A.T.), Hyderabad, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo describe the time course of α4-integrin receptor desaturation and disease activity return in patients with relapsing-remitting MS who discontinued natalizumab and to investigate baseline and on-study predictors for the recurrence of disease activity.

methodsIn the course of TOFINGO, a 32-week, patient- and rater-blinded multicenter, parallel-group study, we performed MRI, counted relapses, and measured α4-integrin receptor occupancy (RO) at baseline and 8, 12, 16, 20, and 24 weeks. The relationship between RO and total number of new T1 gadolinium-enhancing (Gd+) lesions was modeled using Poisson linear regression.

resultsPatients (N = 142) were randomized (1:1:1) to 8-, 12-, or 16-week washout (WO) groups. At randomization, the median RO in the 8-, 12-, and 16-week WO groups was 94.5%, 92.4%, and 90.9%, which declined to 79.8%, 30.7%, and 8.7% after 8, 12, and 16 weeks of WO, respectively. The percentage of patients with new T1 Gd+ lesions increased with longer WO period before commencing fingolimod: 2.1% (8 weeks), 9.1% (12 weeks), and 50.0% (16 weeks). Overall, 71% of patients with first relapse between weeks 6 and 18 had RO values below the time-matched population median. Higher T2 lesion volume (LV) at baseline predicted a higher number of new T1 Gd+ lesions.

conclusionsA faster decline in natalizumab RO, longer WO period, and higher T2 LV at baseline were associated with an increased risk for return of inflammatory disease activity. These results provide a mechanistic rationale and, together with the main outcomes of the TOFINGO study, support initiation of fingolimod within 8 weeks of natalizumab discontinuation. CLINICALTRIALSGOV IDENTIFIER: NCT01499667.

Identifiers

PMID28856176
PMCPMC5572051

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.