Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial

Abstract

Background:Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis.Methods:The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan–Meier method.Results:Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2–16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69–0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%–82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%–55.4%]; and low-risk group, 20.8% [95% CI, 14.2%–26.8%]; log-rank P < 0.001).Conclusions:This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.

Development of a predictive model for predicting disability after optic neuritis: a secondary analysis of the Optic Neuritis Treatment Trial

“…In the ONTT, high-dose intravenous methylprednisolone may reduce the risk of MS occurrence ( 22 ), and in theory, this decrease may also lower the risk of disability. However, our analysis did not observe such an occurrence, so further research is needed to investigate the actual impact of corticosteroid therapy on disability.…”

“…In our finding, we observed that patients with optic neuritis who had clinically definite MS at baseline had a higher risk of developing disability compared to those who were not diagnosed with MS. In the ONTT, high-dose intravenous methylprednisolone may reduce the risk of MS occurrence (22), and in theory, this decrease may also lower the risk of disability. However, our analysis did not observe such an occurrence, so further research is needed to investigate the actual impact of corticosteroid therapy on disability.…”

“…The candidate variables in the model were selected based on clinical relevance, prior research ( 22 ), and data availability. These variables included age, sex, number of lesions on MRI, treatment group (intravenous, placebo, and prednisone), visual acuity of the affected eye, the baseline condition of the optic disk in the affected eye, pain status of the affected eye, the presence or absence of the optic disk or peripapillary hemorrhage in the affected eye, whether the person lived in the north for 10 or more years of the first 15 years of life (with ‘north’ defined as states predominantly located above latitude 40° north), the baseline classification of MS (none, possible, probable, and definite), and prior neurologic symptoms.…”