Patient-Reported Outcomes Are the Strongest Predictors of Disability Progression in Intramuscular Interferon Beta-1a Users in the NYS MS Consortium

Background: The New York State Multiple Sclerosis Consortium (NYSMSC) is a 20-year longitudinal registry of participants with multiple sclerosis (MS). Data suggest that patient-reported outcomes (PROs) may be indicators for disease progression, but their value in predicting long-term outcomes is unclear.

Objectives: To report on long-term outcomes associated with intramuscular interferon beta-1a (IM IFN beta-1a; Avonex) use, and identify early predictors of disability progression, among IM IFN users in the NYSMSC.

Methods: Relapsing-remitting MS (RRMS) patients who reported IM IFN use were extracted from the NYSMSC database. Two groups were created: (1) patients who progressed in their disability over 3 years, defined by an increase in the Expanded Disability Status Scale (EDSS) ≥ 1 point if the baseline EDSS was <6.0, or ≥0.5 points if the baseline EDSS was ≥6.0; and (2) patients with stable disease (no disability progression). Baseline PROs and clinical characteristics were compared between groups using independent samples t-test and chi-square tests to identify associations with disability progression over approximately three years of follow-up. Multivariate logistic regression was performed to generate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of disability progression, adjusted for age, disease duration and baseline EDSS.

Results: Of 1383 RRMS patients in the NYSMSC on IM IFN who met the criteria, 416 (30.1%) had disability progression and 967 (69.9%) remained stable over three years. There were no differences between the progression group and the stable group with respect to age at disease onset, disease duration, sex, race or education. We found that difficulties in getting up (OR: 2.5 [95% CI: 1.6-4.1]), standing (OR: 2.8 [95% CI: 2.1-3.7]), and lower limb use (OR: 2.4 [95% CI:1.6-3.7] for those who reported moderate-severe lower limb limitations) were all highly associated with disability progression (all p-values <0.001). For clinical measure, the timed 25-foot walk (T25FW) showed a weaker association with disability progression (OR: 1.1 [95% CI: 1.1-1.3]; p<0.001).

Conclusions: In the NYSMSC, among RRMS patients on IM IFN, difficulties getting up, standing and lower limb use at baseline were the strongest predictors of disability progression over three years; the T25FW showed a weaker association. Further research is needed to determine additional predictors of responders.