DX75
Development of Chronic Black Holes (CBH) Predicts Long Term Disability: Post-Hoc Analysis of Magnetic Resonance Imaging Data (MRI) in the Prisms Study
Objectives: Assess the effect of subcutaneous (sc) interferon β-1a (IFN β-1a) on evolution of gadolinium-enhancing (Gd+) lesions into CBH in patients with relapsing–remitting MS (RRMS) and the predictive value of CBH on long-term disability.
Methods: Retrospective analysis of MRI scans of patients in the PRISMS study (RRMS; baseline Expanded Disability Status Scale [EDSS] score 0–5.0) who were randomized to IFN β-1a, 44 or 22 μg three times weekly or placebo; after 2 years, placebo patients were re-randomized to IFN β-1a 44 or 22 μg (delayed treatment [DT]). Patients with monthly scans from Months -1 to 9 and ≥1 new enhancing lesions (NEL) from Months -1 to 3 were included; CBH evolving from NEL were assessed at Month 8/9. Association between CBH and disability outcome at 4 years follow-up was analyzed according to treatment group.
Results: 196 patients were included (IFN β-1a combined, n=129; DT, n=67). In the IFN β-1a group, 73/129 (57%) had NEL from Months -1 to 3 versus 49/67 (73%) in the DT group; ≥1 CBH at Month 8/9 developed in 25/73 (34%) and 27/49 (55%) patients with ≥1 NEL, respectively. For patients who developed CBH (CBH+) a higher proportion (55.8%) experienced disability progression (confirmed 3-month Expanded Disability Status Scale [EDSS] progression rate at 4 years) than those who did not (CBH-, 43.1%). For CBH+ patients, proportions with confirmed EDSS progression at 1-, 2-, 3- and 4-years were: DT 37.0%, 48.1%, 55.6%, and 59.3%, respectively; IFN β-1a 12.0%, 32.0%, 52.0%, and 52.0%, respectively. Fewer CBH- patients showed confirmed EDSS progression at 1-, 2-, 3- and 4-years: DT 35.0%, 37.5%, 37.5%, and 45.0%; respectively; IFN β-1a 21.2%, 29.8%, 39.4%, and 42.3%, respectively. For CBH+ patients, median EDSS score in the DT group increased from 2.0 at Month 8/9 to 3.5 at 4 years; in the IFN β-1a group, the score increased from 2.5 to 3.0. For CBH- patients, median EDSS scores at Month 8/9 and 4 years were: DT from 2.0 to 2.5 and IFN β-1a from 2.0 to 2.0, respectively.
Conclusions: CBH development in the first 9 months was associated with greater disability progression at 4 years, regardless of whether patients received treatment. However, treatment with sc IFN β-1a was associated with a decreased proportion of NEL evolving into CBH, and slower progression of disability at 4 years.
The authors would like to acknowledge Guojun Zhao, Yan Cheng and Andrew Riddehough (University of British Columbia, Vancouver, BC, Canada) for their contributions to the analysis.