Intrathecal Interferon Benefits Devastating Post-Measles Syndrome

Daniel M. Keller, PhD

October 30, 2019

DUBAI, United Arab Emirates — Intrathecal interferon-α2B (IT-IFN) appears to be a safe and efficacious treatment option for patients with subacute sclerosing panencephalitis (SSPE), a devastating, progressive illness of the central nervous system that occurs in children and young adults.

IT-IFN is an especially attractive treatment option when isoprinosine is not available or its use is not feasible.

Speaking here at the XXIV World Congress of Neurology (WCN), Hardeep Malhotra, MD, DM, of King George's Medical University in Lucknow, India, explained that SSPE is a persistent infection of the brain caused by an aberrant measles virus after measles infection. Patients usually exhibit behavioral changes, myoclonus, mental deterioration, seizures, extrapyramidal dysfunction, and visual disturbances.

It is estimated that 20 million cases of measles occur worldwide each year, with 197,000 deaths from all measles-related causes. More than half of these deaths occur in India, he said.

With no specific or definitive therapy for SSPE, a combination of oral isoprinosine and intraventricular IFN is considered the most effective treatment. But isoprinosine is costly and is not currently listed with the national drug regulatory body of India.

IT-IFN is inexpensive, costing approximately $8 per injection, and may be associated with less risk for infection than intraventricular IFN.

Malhotra therefore conducted a single-center, open-label, randomized study of IT-IFN that included 47 patients with SSPE. Of those patients, 24 received IT-IFN, and 23 served as controls. Patients with Jabbour stage 4 disease were excluded because significant improvement would not be expected for those patients.

Six million units of IT-IFN were given weekly for 6 weeks and then monthly for 6 months. Antiepileptic drugs were used for patients having myoclonic jerks or other types of seizures. Patients were premedicated with acetaminophen and ibuprofen before receiving IT-IFN.

At baseline, the IT-IFN and control groups were well matched for sex (approximately 80% male), age (11–12.4 years), duration of illness (7.5–10.3 months), scores on the modified Rankin Scale (mRS; 2.79–2.87), neurologic measures, signs, symptoms, and Jabbour stage (majority, stage 3).

In the IT-IFN group, 54.2% had measles at <2 years of age (83.3% unimmunized), vs 56.5% in the control group (87% unimmunized).

Patients who received IT-IFN significantly benefited on several measures compared with control patients, notably in terms of mRS, Barthel index of activities of daily living, and Jabbour stage.

Table. Outcomes at 7.5 Months

Characteristic Interferon Group Control Group P Value
Modified Rankin scale ≤2 8 (33.3%) 3 (13%) .101
Modified Rankin scale (mean ± SD) 2.91 ± 0.89 3.87 ± 1.14 .014
Barthel index (mean ± SD) 47.08 ± 33.55 11.30 ± 19.37 .009
Glasgow coma scale (mean ± SD) 14.0 ± 2.04 11.57 ± 3.90 .286
Jabbour stage
Improvement 6 (25%) 1 (4.3%) .007
Stabilization 15 (62.5%) 10 (43.5%)
Progression 3 (12.5%) 12 (52.2%)
CSF antimeasles antibody titer
Improvement 9 (37.5%) 2 (8.7%) .03
Stabilization 11 (45.8%) 11 (47.8%)
Progression 4 (16.7%) 10 (43.5%)

 

Malhotra recommended that a multicenter study be conducted to explore IT-IFN dosage options to possibly enhance the outcomes seen in this study.

"Dreadful Death"

Session co-chair Raad Shakir, MBChB, of Imperial College London, United Kingdom, who is the immediate past-president of the World Federation of Neurology, told Medscape Medical News that he is very concerned about the resurgence of measles around the world.

"It is a preventable disease, and vaccinations are not being used, for me, for no logical reason at all," he said. "And this will only lead to conditions which we thought have disappeared from the world, and people have to realize that although this is rare, it's fatal. When you get SSPE, you're not going to survive."

He explained that the duration of the disease may be 2 or more years. "It is a dreadful death for a child ― total disability and the dreadful death."

Use of isoprinosine, when it is is available and is affordable, does not alter the eventual outcome, he noted.

Even if patients survive 5 or 6 years, "that survival is misery, bedridden, being fed through other means and [with] seizures," he said. "Children 9, 10, 11 years old do not speak, do not eat, do not move, totally bedridden, and it's a condition I dread when I see the measles incidence is increasing in Western countries, and for no good reason, for as far as I'm concerned.... One of the greatest achievements of medicine is vaccination."

The study received no outside funding. Malhotra and Shakir have disclosed no relevant financial relationships.

XXIV World Congress of Neurology (WCN): Presented October 27, 2019.

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