The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis

Abstract

Background: Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-beta-1b decreases the formation of CELs. However, the ability of IFN-beta-1b to reduce the size of CELs arising during therapy has not been extensively investigated.

Methods: Thirty patients with relapsing-remitting (RR) MS were followed for a 3-month pre-therapy phase then for a 6-month therapy phase during which treatment with IFN-beta-1b at a dosage of 250 microg subcutaneously injected every other day was employed. Each patient underwent monthly clinical and MRI examinations. For all patients, CELs were identified on postcontrast T1-weighted MRIs. CEL number, size, and volume were computed using Medx software.

Results: The average number and total lesion volume of CELs visible during the therapy phase were significantly lower than the number and total lesion volume of CELs observed in the pre-therapy phase. However, there was no significant reduction between pre-therapy and therapy phases in the mean size of individual lesions arising during the respective phases.

Conclusions: Since size of CELs has been related to severity of tissue damage, the lack of size decrease during therapy suggested a limited therapeutic effect of IFN-beta-1b if a blood-brain barrier breakdown has occurred.

Figure 1. Square root of average monthly lesion number during pre-therapy phase and therapy phase

Each line represents the data collected from one patient. The lines consist of two points: the first point represents the average monthly lesion count over the pre-therapy phase, while the second point is the average lesion count throughout the duration of the therapy phase. Square root values were taken to moderate the effects of extremely large changes and allow the data to better fit a normal distribution. The number of lesions decreased during treatment (p < 0.0001).

Figure 2. Square root of averaged monthly total lesion volume during pre-therapy phase and therapy phase

Each line represents the data collected from one patient. The lines consist of two points: the first point represents the average monthly total lesion volume (Figure 2) over the pre-therapy phase, while the second point is the average lesion volume throughout the duration of the therapy phase. Square root values were taken to moderate the effects of extremely large changes and allow the data to better fit a normal distribution. The total lesion volume decreased during treatment (p < 0.0001).

Figure 3. Individual lesion size (log transformed) for a subset of short-duration lesions

Each dot represents the log transformed size of a lesion; some lesions were measured only once while others and were measured twice. Lesions measured twice have volumes connected by a line. Lesions in the pre-therapy phase (indicated as months –2 –0 in this figure) were chosen so they ended prior to month 3 and therefore could not have been affected by treatment and are of 1- or 2-month duration. A comparison group of lesions initially appearing in the therapy period (months +1 – +6) were chosen to have similar short duration of no more than 2 months. Only CELs whose origin was identified at month –1 or –2 were considered. Similarly, any CEL that was present at months +5 or +6 of the therapy phase was tracked onward in time in the following MRIs and kept in the analysis if they lasted no longer than three observations.