Kids with MS need prompt treatment


Last Updated: 2010-12-13 18:43:05 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - About half of children with multiple sclerosis (MS) need to switch medication during their first few years of treatment because of refractory illness or poor tolerability, new study results show.

"The general rule of thumb is to wait until more than one relapse has occurred to change therapies," lead author Dr. E. Ann Yeh said. But she advises that physicians shouldn't be afraid to change treatment if the patient's disability worsens or the tempo of relapses increases.

She also recommends that pediatric MS patients be treated as soon as the diagnosis is firm, usually after two clinical episodes of central nervous system demyelination.

In an interview with Reuters Health, the researcher noted that the time to physical disability in kids with MS is longer than in adults, but they "eventually do reach the equivalent to those of adults with secondary progressive MS," and they do so at a younger age. There's also growing evidence that children develop significant cognitive difficulties within several years of diagnosis.

"So if a child is diagnosed with MS, treatment should be initiated sooner rather than later," she said. "Sometimes neurologists tend to wait and watch."

In a paper published online today in the Archives of Neurology, Dr. Yeh, from the Women and Children's Hospital of Buffalo, New York, and colleagues review records of 258 patients with pediatric-onset MS treated between 1997 and 2009 at the six Pediatric MS Centers of Excellence in the US.

The average age of onset was 13.2 years (range 2.0-17.9 years).

The patients initially received at least six months of treatment with a first-line disease-modifying therapy (DMT) - interferon beta (in 77.5%) or glatiramer acetate (in 20.5%). Five patients (1.9%) with very active acute disease were first treated with pulse cyclophosphamide or azathioprine but were later prescribed a first-line DMT.

Most patients (52.3%) continued with the first therapy prescribed throughout the observation period, which averaged 3.9 years. Therapy was changed once in 25.2%, twice in 11.2%, three times in 3.9%, and four or more times in 3.9%. Nine patients (3.5%) quit treatment.

The primary reason for change was refractory disease (clinical relapses, MRI changes, or both) after an average of 1.3 years. The second most common reason was drug intolerance.

Other treatments included broad-spectrum chemotherapies (e.g., cyclophosphamide and mitoxantrone), natalizumab, monthly pulse corticosteroids, daclizumab, intravenous immunoglobulin, azathioprine, and mycophenolate mofetil. Twenty-two patients received combination treatments.

The authors say the relatively frequent use of second-line agents and combination treatment for severe or refractory disease "suggests that pediatric MS may not be a benign disease." Since the long-term safety of these strategies in children is unknown, pediatricians need to be particularly vigilant, the authors warn.

At baseline, the mean Expanded Disability Status Scale score (ranging from 0 -- normal neurologic examination -- to 10 -- death due to MS) was 2.1, which fell to 1.7 at patients' last visits.

Dr. Yeh noted that the International Pediatric MS Study Group, working closely with the Pediatric Centers of Excellence, will soon be releasing consensus guidelines on the treatment of children with refractory MS.

"This is one of the very first papers published about children not responding to first-line treatment," Deborah Hertz, assistant vice president of medical programs for the National MS Society (NMSS), told Reuters Health. The NMSS had a major role in developing the Pediatric Centers of Excellence and the International Study Group.

Hertz noted that pediatric MS is rare - "our best estimate is that 8000 to 10,000 children in the US are affected" - and that until about 5 years ago, "it wasn't even on the radar screen of pediatricians or most neurologists."

In fact, she continued, one factor influencing formation of the network of pediatric centers was hearing from families about affected kids being "bounced around" from one doctor to another, because they weren't aware that MS could occur in children. "So they weren't being diagnosed or treated until they reached adulthood and they 'looked' more familiar to doctors."

"Now there's a sense of urgency with the approval of disease-modifying therapies in the adult population, meaning that early treatment is critically important to slow down the progression of the disease," Hertz said.

Increasing awareness and research on children with MS will affect the entire 400,000-plus population of patients with MS, added Arney Rosenblat, another spokesperson for the NMSS. "We know that MS is caused by a combination of genetic and environmental factors. So it will help to study patients who have presented with symptoms at such a young age, when there's far less environmental 'noise' than in a 40- or 50-year old. This could have a large ripple effect in helping isolate important genetic factors."

SOURCE:http://link.reuters.com/wup89q

Arch Neurol 2010.



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