Monday, January 26, 2009
By Michael Smith, North American Correspondent, MedPage Today
Published: January 12, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
BOSTON, Jan. 12 -- When multiple sclerosis symptoms start in adolescence, the later annual relapse rate is nearly three times as great as it is for adult-onset disease, researchers here said.
The finding suggests that adolescent-onset MS has a more inflammatory disease course, according to Tanuja Chitnis, M.D., of Massachusetts General Hospital, and colleagues.
But the biological basis of the difference remains unclear and requires more study, Dr. Chitnis and colleagues said in the January issue of Archives of Neurology.
Several studies have shown that initial disease progression is slower in patients whose disease begins before the age of 18, the researchers said, but have differed on rates of relapse.
To clarify the issue -- and see whether the slower progression is related to relapse rates -- Dr. Chitnis and colleagues studied patients treated in the pediatric and adult MS centers at Massachusetts General and Brigham and Women's after July 2001.
Patients were eligible if treatment started within 12 months of the first symptom and were followed for at least a year. All told, the researchers identified 110 adult-onset patients and 21 whose disease started before they were 18.
The main outcome measure was annualized relapse rate, defined as the number of relapses divided by the number of person-years at risk. Rates for the adult and younger groups were compared using a proportional means model, as well as a negative binomial regression that excluded the first attack.
In both models, the researchers found that the annualized relapse rate was significantly higher in the younger cohort. Specifically:
* When the first attack was included, adolescent patients had an annualized rate of 1.4, compared with 0.65 for adult-onset patients. The difference was significant at P0.001 and yielded an adjusted rate ratio of 2.81 (with a 95% confidence interval from 2.07 to 3.81.
* Excluding the first attack yielded a pediatric rate of 1.13 and an adult rate of 0.4, also significantly different at P0.001.The adjusted rate ratio was 2.93 (with a 95% confidence interval from 1.93 to 4.46).
When the researchers controlled for the effects of disease-modifying treatment -- such as interferons, glatiramer acetate (Copaxone) or oral immunosuppressants -- the difference remained significant, with rate ratios of 2.82 and 3.02, depending on the model.
And when age was treated as a continuous variable, the age at onset was significantly associated with relapse rate at P0.001, Dr. Chitnis and colleagues found.
While several studies have shown that disease progression is slower in adolescent-onset cases, the researchers said they were unable to show that in this case because of the relatively short disease duration.
But if that is so, Dr. Chitnis and colleagues argued, the finding that younger patients have more relapses implies "greater plasticity, less neurodegeneration, and potentially more repair and remyelination in the younger nervous system."
The authors pointed out that "it remains possible that patients with more severe pediatric-onset MS were selectively evaluated at our centers. However, distance from the center, a proxy measure for referral bias, which has been shown to influence clinical characteristics in prior articles in the neurology and oncology literature, was not different between our pediatric-onset and adult-onset groups."
The study was supported by the National Multiple Sclerosis Society. The researchers did not report any conflicts.
Primary source: Archives of Neurology
Gorman MP, et al "Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis" Arch Neurol 2009; 66(1): 54-59.