Interferon β-1a for optic neuritis patients at high risk for multiple sclerosis

doi:10.1016/S0002-9394(01)01209-0

American Journal of Ophthalmology

Volume 132, Issue 4, October 2001, Pages 463-471

https://doi.org/10.1016/S0002-9394(01)01209-0 Get rights and content

Abstract

PURPOSE: To evaluate the effect of treatment with interferon β-1a (Avonex) initiated at the time of a first episode of optic neuritis in patients at high risk for multiple sclerosis (MS).

DESIGN: Randomized clinical trial

METHODS:

Prospective.

SETTING: Fifty clinical centers throughout the US and Canada.

STUDY POPULATION: After the onset of a first episode of optic neuritis treated with intravenous and oral corticosteroids, 192 patients with brain magnetic resonance imaging (MRI) evidence of subclinical demyelination were randomly assigned to receive weekly intramuscular injections of 30 μg interferon β-1a or placebo.

MAIN OUTCOME MEASURE: The study outcomes were the development of clinically definite MS within 3 years of follow-up and brain MRI changes at 6, 12, and 18 months.

RESULTS: The rates of clinically definite MS and of a combined MS/MRI outcome were lower in the interferon β-1a group than in the placebo group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50, 95% confidence interval 0.34 to 0.73, respectively). Compared with the placebo group, on the 18-month brain MRI the interferon β-1a group had a smaller change from baseline in T2 lesion volume (P = .02), fewer new or enlarging T2 lesions (P < .001), and a lower frequency of Gd-enhancing lesions (P < .001).

CONCLUSION: The clinical and brain MRI results of this trial support initiating interferon β-1a treatment at the time of a first episode of optic neuritis occurring in patients at high risk for MS based on the presence of subclinical brain MRI lesions.

Section snippets

Methods

The study was conducted at 50 clinical centers in the US and Canada. The protocol and informed consent forms were approved by each site’s institutional review board, and all study patients gave written informed consent. Study oversight was provided by an independent data and safety monitoring committee. The protocol, which is summarized below, was previously reported in detail.21

Results

Between April 1996 and April 1998, 192 patients with optic neuritis were enrolled in the trial, with 95 assigned to the interferon β-1a group and 97 assigned to the placebo group (Table 1). The mean age of the patients was 34 years; 80% were women and 85% were white. The 2 treatment groups were well balanced on demographic factors. However, the baseline brain MRI T2 lesion volume and the proportion of patients with Gd-enhanced lesions were higher in the interferon β-1a group than in the placebo

Discussion

Our results show that interferon β-1a treatment, initiated at the time of a first episode of optic neuritis, is beneficial for patients at high risk for MS based on brain MRI evidence of subclinical demyelination. In this study of 192 patients with acute optic neuritis, interferon β-1a reduced both the development of clinically definite MS and the development of new brain MRI lesions. These results for the optic neuritis cohort in CHAMPS are similar to the overall study results, which also

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Cited by (71)

Optic neuritis in paediatric patients: Experience over 27 years and a management protocol
2021, Neurologia
Se presenta nuestra experiencia en neuritis óptica (ON) y se elabora un protocolo diagnóstico-terapéutico, que contempla descartar otras causas, principalmente infecciosas y se elabora una hoja informativa para padres.
Estudio descriptivo retrospectivo de los pacientes con ON en 27 años (1990-2017). Revisión de evidencia científica para elaboración del protocolo y hoja informativa.
En nuestra sección de neuropediatría se valoraron 20.744 niños en 27 años, 14 con ON: 8 ON aisladas, una esclerosis múltiple (EM), un episodio clínicamente aislado (CIS), 3 encefalomielitis agudas diseminadas y un paciente con ON aislada que el año anterior había sufrido una encefalomielitis aguda diseminada. Edades entre 4-13 años, 50% varones. Mayores de 10 años, 8 pacientes: 7 ON aisladas y un EM. Bilaterales 9, retrobulbares 3. Resonancia magnética cerebral normal en 7, solo afectación del nervio óptico en 2 y con desmielinización del SNC en 5 casos. Recibieron corticoterapia 13/14. Un caso vacunado de meningococo-C el mes anterior. Todos evolucionaron favorablemente, salvo la EM. Se presentan el protocolo y la hoja de información.
Habitual curso favorable. En niños a partir de 10 años, con factores de riesgo de desarrollar EM o neuromielitis óptica (presencia de hiperseñales en RM cerebral, bandas oligoclonales, anti-NMO, recurrencia de ON), se consensúa con Neurología el inicio de tratamiento inmunomodulador. Utilidad del protocolo para la toma de decisiones diagnósticas, de seguimiento y tratamiento, de una patología poco frecuente pero con posibles repercusiones importantes. Importancia de la protocolización y hojas informativas.
In this article, we present our experience on optic neuritis (ON) and provide a diagnostic/therapeutic protocol, intended to rule out other aetiologies (particularly infection), and a fact sheet for parents.
We conducted a descriptive, retrospective study of patients with ON over a 27-year period (1990-2017). A review of the available scientific evidence was performed in order to draft the protocol and fact sheet.
Our neuropaediatrics department has assessed 20,744 patients in the last 27 years, of whom 14 were diagnosed with ON: 8 had isolated ON, 1 had multiple sclerosis (MS), 1 had clinically isolated syndrome (CIS), 3 had acute disseminated encephalomyelitis, and 1 had isolated ON and a history of acute disseminated encephalomyelitis one year previously. Patients’ age range was 4-13 years; 50% were boys. Eight patients were aged over 10: 7 had isolated ON and 1 had MS. Nine patients had bilateral ON, and 3 had retrobulbar ON. MRI results were normal in 7 patients and showed involvement of the optic nerve only in 2 patients and optic nerve involvement + central nervous system demyelination in 5. Thirteen patients received corticosteroids. One patient had been vaccinated against meningococcus-C the previous month. Progression was favourable, except in the patient with MS. A management protocol and fact sheet are provided.
ON usually has a favourable clinical course. In children aged older than 10 years with risk factors for MS or optic neuromyelitis (hyperintensity on brain MRI, oligoclonal bands, anti-NMO antibody positivity, ON recurrence), the initiation of immunomodulatory treatment should be agreed with the neurology department. The protocol is useful for diagnostic decision-making, follow-up, and treatment of this rare disease with potentially major repercussions. The use of protocols and fact sheets is important.
A novel decision tree approach to predict the probability of conversion to multiple sclerosis in Iranian patients with optic neuritis
2021, Multiple Sclerosis and Related Disorders
Citation Excerpt :
It is needless to emphasize that the ability to predict the conversion to MS in each case not only helps to individualize the patient's management but also is an invaluable tool to design studies that are focusing on the prevention of MS after ON attack. The presence of a specific type of plaque in patients with ON was sufficient enough to prescribe interferon β-1a and Glatiramer acetate in multiple studies.9, 10, 17 It might be possible to narrow the drug candidates list based on the probability of conversion to MS in the future studies to select the patients who benefit the most from these types of preemptive interventions.
Background: assessing the risk of conversion to multiple sclerosis (MS) in patients with optic neuritis (ON) has been the topic of numerous studies. However, since the risk factors differ from population to population, the extension of conclusions is a matter of debate. This study focused on the Iranian patients with optic neuritis and assessed the probability of conversion to multiple sclerosis by using a machine-based learning decision tree.
Methods: in this retrospective, observational study the medical records of patients with optic neuritis from 2008 to 2018 were reviewed. Baseline vision, the treatment modality, magnetic resonance imaging (MRI) findings, and patients’ demographics were gathered to evaluate the odds of each factor for conversion to MS. The decision tree was then obtained from these data based on their specificity and sensitivity to predict the probability of conversion to MS.
Results: the overall conversion rate to MS was 42.2% (117/277). 63.1 percent of patients had abnormal MRIs at baseline. The presence of white matter plaque had the highest odds for the conversion followed by the positive history of optic neuritis attack and gender. The regression tree showed that the presence of plaque was the most important predicting factor that increased the probability of conversion from 16 to 51 percent.
Conclusion: the decision tree could predict the probability of conversion to MS by considering multiple risk factors with acceptable precision.
Neuro-oncology dilemma: Tumour or tumefactive demyelinating lesion
2015, Multiple Sclerosis and Related Disorders
Citation Excerpt :
Bearing this in mind, the largest and most rigorous study of patients with TDLs examined 168 patients with biopsy confirmed disease (Lucchinetti et al., 2008). In that study, patients with both MS and non-MS associated TDL, the time to a second event in patients presenting with a TDL as their first clinical event (i.e. fulfilling dissemination in time) was 4.8 years compared with 1.9–3 years for a typical demyelinating event (CHAMPS Study Group, 2001; Confavreux and Vukusic, 2002; Placebo-controlled, 1998). However, the presence of TDLs did not appear to greatly impact the overall prognosis of MS. There was a slight trend for more favourable prognosis in those patients with TDLs when accompanied by more typical MS demyelinating lesions on MRI.
Tumefactive demyelinating lesions (TDLs) are not an uncommon manifestation of demyelinating disease but can pose diagnostic challenges in patients without a pre-existing diagnosis of multiple sclerosis (MS) as well as in known MS patients. Brain tumours can also arise in MS patients and can be seen in chronic MS patients as co-morbidities. Delayed diagnosis or unnecessary intervention or treatment will affect the ultimate prognosis of these patients. In this article, we will review some typical cases illustrating the dilemma and review the information that helps to differentiate the two conditions.
The intention is not to present an extensive differential diagnosis of both entities, but to examine some typical examples when the decision arises to decide between the two. We take a somewhat different approach, by presenting the cases in “real time”, allowing the readers to consider in their own minds which diagnosis they favour, discussing in detail some of the pertinent literature, then revealing later the actual diagnosis. We would urge readers to consider re-visiting their first thoughts about each case after reading the discussion, before reading the follow-up of each case.
The overall objective is to highlight the real possibility of being forced to decide between these two entities in clinical practise, present a reasonable approach to help differentiate them and especially to focus on the possibility of TDLs in order to avoid unnecessary biopsy.
Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI
2014, Journal of Clinical Neuroscience
Citation Excerpt :
When these factors are present, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended, at least during the first 5 years. Early immunomodulatory treatment may be considered as it can prevent or delay conversion, reduce the development of new subclinical lesions and improve the clinical outcome [4–10]. Treatment decision must be individualized and reserved for high risk patients, as some patients will never develop MS.
When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p = 0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p = 0.004) and incomplete visual acuity recovery (⩽6/12) after 1 year (p = 0.002). Lower conversion rates were found in patients with optic disc edema (p = 0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate.
Optic Neuritis
2014, Encyclopedia of the Neurological Sciences
Inflammation of the optic nerve can have primary or secondary causes. Most optic neuritis is primary and demyelinating and is recognized as one of the clinically isolated syndromes suggestive of multiple sclerosis (MS). The diagnosis of optic neuritis is clinical and based on specific symptoms and signs. An organized approach to the investigation, treatment, and follow-up of patients with optic neuritis is essential and includes an understanding of important secondary causes.
Visual issues in multiple sclerosis
2013, Physical Medicine and Rehabilitation Clinics of North America

View all citing articles on Scopus

^☆: This study was supported by Biogen, Inc., Cambridge, Massachusetts.

^e1: [email protected]

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Original articleInterferon β-1a for optic neuritis patients at high risk for multiple sclerosis☆

Abstract

Section snippets

Methods

Results

Discussion

Lancet

Clin Ther

Optic neuritis or multiple sclerosis

Arch Neurol

Optic neuritis and multiple sclerosis

Arch Neurol

The five-year risk of multiple sclerosis after optic neuritisexperience of the Optic Neuritis Treatment Trial

Neurology

Correlation of clinical, magnetic resonance imaging, and cerebrospinal fluid findings in optic neuritis

Ann Neurol

The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis

Brain

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10 year follow-up

Brain

Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination

Neurology

Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group

Arch Neurol

Magnetic resonance imaging of the brain in patients with acute monosymptomatic optic neuritis

Acta Neurol Scan

Clinical and magnetic resonance imaging in optic neuritis

Neurology

Silent brain lesions in patients with isolated idiopathic optic neuritis. A clinical and nuclear magnetic resonance imaging study

Arch Neurol

Disseminated lesions at presentation in patients with optic neuritis

J Neurol Neurosurg Psychiatry

Original article
Interferon β-1a for optic neuritis patients at high risk for multiple sclerosis☆