Highlights
- •Certain features of multiple sclerosis relapses predict impending progression.
- •A fundamental relationship is derived from a representative multiple sclerosis cohort.
- •A prediction score grades the yearly risk of secondary progression between 1% and 15%.
- •This clinically useful score is calculated from current age and recent clinical data.
- •It defines periods of increased disease activity and may prompt induction therapy.
Abstract
Background
Prediction of the course of multiple sclerosis (MS) was traditionally based on features
close to onset.
Objective
To evaluate predictors of the individual risk of secondary progression (SP) identified
at any time during relapsing-remitting MS.
Methods
We analysed a database comprising an untreated MS incidence cohort (n=306) with five decades of follow-up. Data regarding predictors of all attacks (n=749) and demographics from patients (n=157) with at least one distinct second attack were included as covariates in a Poisson
regression analysis with SP as outcome.
Results
The average hazard function of transition to SPMS was 0.046 events per patient year,
showing a maximum at age 33. Three covariates were significant predictors: age, a
descriptor of the most recent relapse, and the interaction between the descriptor
and time since the relapse. A hazard function termed “prediction score” estimated
the risk of SP as number of transition events per patient year (range <0.01 to >0.15).
Conclusions
The insights gained from this study are that the risk of transition to SP varies over
time in individual patients, that the risk of SP is linked to previous relapses, that
predictors in the later stages of the course are more effective than the traditional
onset predictors, and that the number of potential predictors can be reduced to a
few (three in this study) essential items. This advanced simplification facilitates
adaption of the “prediction score” to other (more recent, benign or treated) materials,
and allows for compact web-based applications (http://msprediction.com).
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A prospective study on the prognosis of multiple sclerosis.Neurol Sci. 2000; 21: S831-S838
- Natural history of multiple sclerosis.in: Raine C. McFarland H.F. Hohlfeld R. Multiple sclerosis: a comprehensive text. Saunders Elsevier, Edinburgh2008: 100-120
- In-vivo evidence for stable neuroaxonal damage in the brain of patients with benign multiple sclerosis.Mult Scler. 2009; 15: 789-794
- Early prediction of the long term evolution of multiple sclerosis: the Bayesian Risk Estimate for Multiple Sclerosis (BREMS) score.J Neurol, Neurosurg, Psychiatry. 2007; 78: 757-759
- Statistical methods in cancer research. Volume II – the design and analysis of cohort studies.IARC Sci Publ. 1987; : 1-406
- Natural history of multiple sclerosis: a unifying concept.Brain. 2006; 129: 606-616
- Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process.Brain. 2003; 126: 770-782
- Prognosis of the individual course of disease--steps in developing a decision support tool for Multiple Sclerosis.BMC Med Inform Decis Mak. 2007; 7: 11
- Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis.Mult Scler (Houndmills, Basingstoke, England). 2003; 9: 260-274
- Remyelination in the CNS: from biology to therapy.Nat Rev Neurosci. 2008; 9: 839-855
- A web-based tool for personalized prediction of long-term disease course in patients with multiple sclerosis.Eur J Neurol. 2013; 20: 1107-1109
- Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden.Osteoporos Int. 2012; 23: 991-999
- Development and use of FRAX in osteoporosis.Osteoporos Int. 2010; 21: S407-S413
- How to decide who to treat.Best Pract Res Clin Rheumatol. 2009; 23: 711-726
- The evolution of multiple sclerosis epidemiology.Ann Neurol. 1994; 36: S2-S5
- Cortical demyelination and diffuse white matter injury in multiple sclerosis.Brain. 2005; 128: 2705-2712
- Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.Arch Neurol. 2006; 63: 1686-1691
- Progressive multiple sclerosis: pathology and pathogenesis.Nat Rev Neurol. 2012; 8: 647-656
- Long-term survival of patients with multiple sclerosis in West France.Mult Scler (Houndmills, Basingstoke, England). 2007; 13: 865-874
- Prognostic factors for survival in multiple sclerosis.Mult Scler. 1999; 5: 171-178
- The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects.Diabetologia. 2010; 53: 1093-1098
- Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis.Neurology. 1996; 46: 907-911
- Fracture risk assessment.Clin Biochem. 2012; 45: 887-893
- Clinically isolated syndromes with no further disease activity suggestive of multiple sclerosis at the age of population life expectancy.Mult Scler (Houndmills, Basingstoke, England). 2014; 20: 496-500
- New diagnostic criteria for multiple sclerosis: guidelines for research protocols.Ann Neurol. 1983; 13: 227-231
- Poisson regression in epidemiology.Encyclopedia of biostatistics. 2005
- Predicting responders to therapies for multiple sclerosis.Nat Rev Neurol. 2009; 5: 553-560
- Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up.Brain. 1993; 116: 117-134
- Prediction of outcome in multiple sclerosis based on multivariate models.J Neurol. 1994; 241: 597-604
- Clinical epidemiology: a basic science for clinical medicine. Little, Brown Co., Boston1991
- Mortality in patients with multiple sclerosis.Neurology. 2013; 81: 184-192
- Onset of secondary progressive phase and long-term evolution of multiple sclerosis.J Neurol Neurosurg Psychiatry. 2014; 85: 67-75
- The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability.Brain. 2010; 133: 1914-1929
- Short-term prognosis in early relapsing-remitting multiple sclerosis.Neurology. 2000; 55: 689-693
- Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis.Brain Pathol. 2004; 14: 164-174
- A representative cohort of patients with non-progressive multiple sclerosis at the age of normal life expectancy.Brain. 2012; 135: 900-911
- Overfitting in prediction models – is it a problem only in high dimensions?.Contemp Clin Trials. 2013; 36: 636-641
- Time to onset of secondary progression as an outcome in MS trials: a new paradigm?.J Neurol Neurosurg Psychiatry. 2014; 85: 3
- Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs.Mult Scler (Houndmills, Basingstoke, England). 2013; 19: 765-774
- Disability progression in multiple sclerosis is slower than previously reported.Neurology. 2006; 66: 172-177
- Impact of multiple sclerosis relapses on progression diminishes with time.Neurology. 2009; 73: 1616-1623
- The Fracture Risk Assessment Tool (FRAX(R)): applications in clinical practice.J Womens Health (Larchmt). 2011; 20: 525-531
- The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course.Brain. 1989; 112: 1419-1428
- The natural history of multiple sclerosis: a geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials.Brain. 1991; 114: 1057-1067
- Need for a paradigm shift in therapeutic approaches to CNS injury.Expert Rev Neurother. 2012; 12: 409-420
- Prognostic factors of multiple sclerosis in Lebanon.Int J Neurosci. 2010; 120: 206-210
Article info
Publication history
Published online: May 08, 2014
Accepted:
April 12,
2014
Received in revised form:
March 23,
2014
Received:
December 18,
2013
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
