Monday, October 7, 2013

In Summary: Treat Multiple Sclerosis or MS-like isolated presentations early and have a better outcome

I will summarize the recent abstract (NOT a formal published study yet, but presented at one of the largest yearly MS meetings in the world), almost 2000 patient charts were reviewed and followed for 3 years on average. These were all patients with Clinically Isolated Syndrome (CIS) which is essentially, a first-time MS-like demyelinating event somewhere in the brain or spinal cord. But it is technically NOT Multiple Sclerosis... yet.

Traditionally these patient were not treated and followed to see if it happened again, and if it did, ONLY then were they treated as MS patients would be.

This study confirmed what many of us have already been shouting: If you suspect a hint of demyelination, treat early and treat thoroughly. Time is brain/spinal cord, and the earlier you treat AND more cvonsistently you treat, the better the LONG TERM outcome is. This is true for CIS as well as definitive MS. No one has been arguing the MS side of that truth, but this study just helped confirm the CIS side as well.

I would make this argument, and I believe many neurologists already are as well: We should not call it Clinically Isolated Syndrome (CIS).... but something like Initial Multiple Sclerosis (IMS) or Evolving Multiple Sclerosis (EMS) or something (for some reason we love acronyms in medicine). At least this would help deter clinicians from waiting to treat it aggressively.

Below is an expanded summary of the article:

COPENHAGEN – Patients who received early and consistent disease modifying treatment at the first signs of multiple sclerosis – often called clinically isolated syndrome (CIS) – appeared to have a slower progression to disability than patients who were treated mainly for additional MS exacerbations, researchers reported here.
Over a 12-month period, patients treated 50% to 80% of the time following the first CIS event reduced their risk of progression -- as measured by the Expanded Disability Status Scale score -- by 45% compared with patients who received disease-modifying treatments less than 50% of the time or not at all (95% CI 0.39-0.79, P=0.001), and patients treated for more than 80% of the time following diagnosis reduced their risk of disability progression by 68% (95% CI 0.22-0.49, P<0.001), said Vilija Jokubaitis. PhD, medical research scientist, University of Melbourne. 
"What was very interesting about this finding was that the patients who appeared to be worse after their CIS and MRI evaluation and who were treated early, did better than patients whose treatment was delayed," she said in her oral Young Investigators report at the annual meeting of the European Association for the Treatment and Research In Multiple Sclerosis.
About three-fourths of these patients were classified on the basis of T2 lesion enhancement as having relapsing-remitting multiple sclerosis at first treatment. Jokubaitis suggested that because their initial examinations looked worse, the patients were treated more aggressively, and that appeared to have long-term benefits in preventing progression.
"Study after study has shown that early treatment with disease-modifying drugs benefits patients with CIS," said Margaret Burnett, MD, assistant clinical professor of neurology and pathology at the University of Southern California in Los Angeles.
"It kills me that some places still are not treating CIS," she said. "These findings presented here are corroborating evidence that we should be treating CIS and we should make every effort to provide continuous treatment."
In the study, Jokubaitis and colleagues reviewed data involving 1,989 patients for whom complete records were available. The patients had a combined 6,724 years of follow-up with a median follow-up of 3 years per patient – ranging from 9 months to 9.9 years.
Of those patients, 1,339 were treated with disease-modifying agents, either interferon-based products or glatiramer acetate (Copaxone). The researchers included 307 patients who had sustained disability progression over 12 months.
The goal of the study was to determine predictors of progression, and the investigators found that advancing age was a weak prognosticator of disability progression – a 17% increased risk per decade (P=0.006). They also found that pyramidal system dysfunction was a strong predictor of disability progression – with higher imaging pathology translating to a 46% increased risk of disease progression (P=0.008).
Jokubaitis acknowledged that teasing out how treatment affected outcomes was confounded by the fact that sicker patients at diagnosis were more likely to be treated early and consistently, which helped them avoid disease progression.
She and her colleagues did scrutinize the different disease-modifying agents used in the study, but found all of them were successful in delaying progression and none appeared significantly better than the other, although treatment with glatiramer acetate approached significance compared with interferon-beta 1a intramuscular injection (P=0.052) in an ad-hoc analysis.
"Cumulative disease-modifying treatment duration significantly delays progression of multiple sclerosis," Jokubaitis said.