Recent studies suggest new therapies for optic neuritis

Brain MR, neurology referrals and early treatment with immune therapy drugs benefit patients with ON and MS.

Issue: January 1, 2001

ByAndrew G. Lee, MD

BySteven L. Galetta, MD

Two recent studies suggest new treatment patterns for optic neuritis. Community ophthalmologists should be aware of the implications of these studies.

Optic neuritis (ON) is a relatively common presenting illness for the general ophthalmologist. ON has a typical clinical profile (Table 1). The Optic Neuritis Treatment Trial (ONTT) was a randomized, placebo-controlled clinical trial that studied the efficacy of corticosteroid treatment for acute ON in adults (n=457 patients). Patients were randomized to the following groups: intravenous (IV) methylprednisolone (MP) followed by oral prednisone; oral prednisone alone; and oral placebo. Previous published recommendations for the evaluation (Table 2) and treatment of ON (Table 3) did not specifically address the role of a consulting neurologist.

ONTT recommendations

Despite the presence of high quality published data from the ONTT, it is not clear that these recommendations have appropriately been applied in clinical practice. Trobe et al performed a survey of the practice patterns of ophthalmologists and neurologists following publication of the ONTT. As the ONTT recommended, clinicians had reduced their use of oral prednisone alone. Two disturbing survey findings were noted, however. First, although IV steroids were being used in ON, they were used in the false belief that IV MP improved final visual outcome. Second, only 7% of neurologists and 36% of ophthalmologists (P=0.0001 ) were following the ONTT recommendation to perform a brain MR scan for treatment decision making. This dissociation between the published evidence and clinical practice is particularly troubling given new information on the treatment of MS with interferons and the possible benefits of early treatment.

Clinical trials

Immunomodulatory therapy (the “ABC drugs”) such as Avonex (interferon beta 1-a, Biogen), Betaseron (beta 1-b, Berlex) and Copaxone (glatiramer acetate, Teva Marion) has been shown to reduce the relapse rate in established MS. The Controlled High-Risk Subject Avonex Multiple Sclerosis Prevention Study (CHAMPS) was a recently published randomized, double masked, clinical trial (n=383 patients) of interferon beta-1a. All patients had a first attack of an acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brainstem or cerebellar syndrome). Enrolled patients had subclinical demyelinating lesions on MR scan of the brain (ie, two or more high signal white matter abnormalities on T2-weighted images). All patients received IV MP followed by randomization to either weekly intramuscular (IM) injections of 30 mcg of interferon beta-la (n=193) or placebo (n=190). The two study end points were the development of clinically definite MS and change in demyelinating lesions on serial brain MR scans. This trial was stopped after a preplanned interim efficacy analysis.

Study results

The cumulative 3-year probability of the development of clinically definite MS was significantly lower in the treatment (interferon beta-1a) group compared to the placebo group (rate ratio, 0.56; 95% confidence interval, 0.38 to 0.81; P=0.002). This rate ratio translates to a 44% reduction in the development of clinically definite MS in the interferon treated group. The treated group also had significant changes on brain MR scans, including relative reduction in the volume of brain lesions (P<0.001), fewer="" new="" or="" enlarging="" lesions="">P<0.001) and="" fewer="" gadolinium-enhancing="" lesions="">P<0.001) at="" 18="">

The CHAMPS trial concluded that treatment with interferon beta-la at the time of a first demyelinating event (including ON) is beneficial for patients with MR lesions compatible with MS. The major implications of the CHAMPS trial for the ophthalmologist are that MR of the brain should be performed on all patients with ON and referral to a neurologist for further evaluation, counseling and possible treatment with IV steroids and interferon beta 1-a for MS is important.

We recommend that ophthalmologists be aware of these study results and be prepared to answer or refer questions from patients about ON and MS. The community ophthalmologist needs to be aware of this change in practice pattern and have a team of caregivers, be they neuro-ophthalmologists or neurologists, that is prepared to offer this therapy.

For Your Information:

Andrew G. Lee, MD, can be reached at the departments of ophthalmology, neurology and neurosurgery at the University of Iowa Hospitals and Clinics, Iowa City, Iowa; (319) 384-7372; fax: (319) 353-7996. Dr. Lee has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Steven L. Galetta, MD, can be reached at the departments of neurology and ophthalmology of the University of Pennsylvania School of Medicine. Dr. Galetta has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

References:

Beck RW, Cleary PA, et al. The effect of corticosteroids for acute optic neuritis in the treatment of acute optic neuritis. N Engl J Med. 1993;326:581-588.

Trobe ID, Sieving PC, et al. The impact of the Optic Neuritis Treatment Trial on the practices of ophthalmologists and neurologists. Ophthalmol. 1999;106(11): 2047-53.

Jacobs LD, Beck RW, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000;343(13):898-904.