Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years
Introduction
Approximately 3–5% of MS patients have onset in childhood (Amato et al., 2010, Amato et al., 2008, Banwell et al., 2011, Boiko et al., 2002, Boster et al., 2009, Chitnis et al., 2009). The course of pediatric-onset MS (POMS) and its relationship to adult-onset MS (AOMS) are important for understanding and managing the disease. Annualized relapse rate (ARR) is an important marker of disease activity, widely used clinically and in clinical trials as a marker of treatment efficacy. Treatment options for adults with MS are rapidly expanding; however none are approved for children (Chitnis et al.,, Chitnis et al., 2012). Thus treatment is currently administered off label and by extrapolation from adult studies. A recent FDA mandate requires that new clinical drug trials include pediatric patients (Chitnis et al., 2013). In preparation, it is essential to better understand the clinical course of POMS, the outcome measures that will be used and their impact on disability. The current data are conflicting, but two of three studies suggest a higher relapse rate among POMS compared to AOMS in the earliest stages of the disease (Chitnis et al., 2009, Duquette et al., 1987, Fog and Linnemann, 1970). Additionally, insights into longer term ARR trends will be useful for trial design given that trials will likely include patients with longer than two years disease duration due to the relative rarity of POMS.
To better understand if higher ARR is sustained beyond 2–3 years after first attack, as we had previously shown (Gorman et al., 2009), we compared ARR between POMS and AOMS patients for up to 6 years of follow-up in our outpatient pediatric and adult MS centers. To identify potential risk factors, we assessed whether age, gender, race or symptoms at onset affected ARR in POMS. The impact of ARR on disability accumulation as measured by EDSS (expanded disability status scale) was also evaluated.
Section snippets
Subjects
Subjects with relapsing remitting onset disease were selected from three cohorts. We defined POMS according to International Pediatric MS Study Group (IPMSSG) diagnostic criteria, with first symptom onset prior to age 18 (Krupp et al., 2007). For POMS subjects, we identified all subjects seen at the Partners Pediatric MS Center, Massachusetts General Hospital (MGH) (n=52) and all subjects seen at the Partners MS Center, Brigham and Women's Hospital (n=32) whose first symptoms occurred prior to
Demographics
Demographic characteristics of POMS and AOMS patients are provided in Table 1. POMS patients were less likely to be white and more likely to be Hispanic (p<0.0001 for each comparison). No significant differences between the groups were observed in gender, disease duration at first visit, or time to treatment initiation (p>0.3 for each comparison), although there were significantly more AOMS patients who initiated treatment prior to their second attack compared to POMS.
In terms of first symptom
Discussion
We expand on the finding of our initial study reporting relapses to be 2.81 times more frequent in POMS compared to AOMS in the 3 years after disease onset (Gorman et al., 2009). Our current study expands on the patient volume and follow-up time to 6 years and demonstrates a comparative adjusted risk ratio of 2.30 overall. ARR in POMS was significantly higher for each year except year 4, which is attributed to random variation in the data. As well, we explore relapse effects on disability
Contributions
Leslie A. Benson—conceptualization, data collection, data interpretation, manuscript drafting and manuscript revision.
Brian C. Healy—conceptualization, data interpretation, data analysis, manuscript drafting and manuscript revision.
Mark P. Gorman—conceptualization and manuscript revision.
Natalie F. Baruch—data collection and manuscript revision.
Taha Gholipour—data collection and manuscript revision.
Alexander Musallam—data analysis and manuscript revision.
Tanuja Chitnis—conceptualization,
Sponsorship/funding
Supported by the National Multiple Sclerosis Society (TC-RG-4256A4/2/) and the Pediatric MS Regional Centers of Excellence Grant from the National MS Society (TC).
Disclosures
Dr. Benson received a National MS Society Clinical Care Fellowship.
Dr. Healy receives Grant support from Merck Serono for work on the CLIMB study at Partners MS Center.
Dr. Gorman reports no disclosures.
N.F. Baruch reports no disclosures.
Dr. Gholipour received Grant support from Merck Serono for work on the CLIMB study at Partners MS Center.
A. Musallam reports no disclosures.
Dr. Chitnis receives Grant support from Merck Serono for work on the CLIMB study at Partners MS Center; has done
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