Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

Abstract

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.

Keywords: MRI; disability progression; multiple sclerosis; relapses.

Figure 1

Comparison between observed frequencies of worsening diseases and month of observation when no relapse was ever recorded. The upper pane uses the complete set of observations (green; label at y = 1 is “All”), the middle pane uses first- and second-line treatment (label at y = 1; first-line, dark brown; second-line, dark blue), and the lower pane uses drug (label at y = 1; Fingolimod, red, FTY; Glatiramer Acetate, dark blue, GLA; Interferon, blue, INF; Natalizumab, light brown, NAT). Abundance is represented by transparency and the figure at the top of each bar. The error bar represents the standard error estimated as p × (1 − p)/n, with p being the number of positives and n the total number of observations. DMT: disease-modifying therapy.

Figure 2

Comparison of disease worsening and one relapse during the first year of treatment (between 6 and 12 months). Colors are for: R0 = no relapse, R1 = relapse during the first year.

Figure 3

Comparison between disease worsening and three scenarios: R0 (no relapse), R1 (relapse during the first year), and R2 (relapse during the second year).

Figure 4

Comparison between MRI activity and the three scenarios: R0 (no relapse), R1 (relapse during the first year), and R2 (relapse during the second year).

Figure 5

Comparison between the observed frequencies of MRI activity and month of observation when no relapse was ever recorded. The upper pane uses the complete set of observations (green; label at y = 1 is “All”), the middle pane uses first- and second-line treatment (label at y = 1; first-line, dark brown; second-line, dark blue), and the lower pane uses the drug (label at y = 1; Fingolimod, red, FTY; Glatiramer Acetate, dark blue, GLA; Interferon, blue, INF; Natalizumab, light brown, NAT). DMT: disease-modifying therapy.

Figure 6

Patients with evidenced disease progression: the proportion of estimations derived from observation of patients never associated with any relapses or brain MRI activity between 12 and 60 months from the prescription start. The upper pane uses the complete set of observations (green; label at y = 1 is “All”), the middle pane uses first- and second-line treatment (label at y = 1; first-line, dark brown; second-line, dark blue), and the lower pane uses the drug (label at y = 1; Fingolimod, red, FTY; Glatiramer Acetate, dark blue, GLA; Interferon, blue, INF; Natalizumab, light brown, NAT). The error bar represents the standard error estimated asp × (1 − p)/n, with p being the number of positives and n the total number of observations. DMT: disease-modifying therapy.