8-year follow-up results from PRISMS trial

The results of 8-year follow-up of MS patients on interferon beta-1a in the PRISMS trial suggest that early high-dose therapy provides sustained benefits over delayed therapy, according to the report authors.PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) was a randomised, double-blind trial comparing subcutaneous IFNβ-1a (22 µg or 44 µg three times weekly) and placebo. Patients were randomised and treated for two years. After this time, patients originally randomised to placebo were re-randomised to one of the two IFN doses and followed for a further two years. All patients who completed the first four years could then continue treatment (blinded or open-label) for another two years and then continue open-label therapy until the long-term follow-up assessment (7-8 years after enrolment). The 2-year, 4-year and 6-year results have previously been reported.The long-term follow-up assessment was conducted on 68.2% of the patients originally enrolled in PRISMS (382 of 560 patients); three hospitals originally participating in PRISMS chose not to participate in the long-term follow-up, reducing the number of patients able to return for long-term assessment. In the long-term follow-up (LTFU) cohort, 72% (275 or 382) were still receiving IFNβ-1a SC three times weekly. The investigators found that patients originally randomised to the 44 ųg IFN dose showed delayed disability progression, lower relapse rate, and lower T2 burden of disease compared to those originally randomised to placebo who began treatment 2 years after enrolment. They say that this suggests that patients can experience sustained benefit from early therapy compared to delayed therapy. Overall, 19.7% (75 of 381) patients progressed to secondary progressive MS between baseline and long-term follow-up, which the authors say may be better than expected, compared to other published data. More LTFU patients on the lower dose were NAb-positive than those on the higher dose. Fewer patients were NAb-positive at long-term follow-up than at earlier assessment, and the authors say, "The results confirm that if NAbs develop, they normally do so early in the course of treatment and indicate that positive status can be lost with long-term treatment." It has already been shown however that over the first four years of the PRISMS study, those patients who were shown to be NAb-positive experienced reduced efficacy on relapse rate and MRI until year 4 when the NAb-positive and NAb-negative groups converged.Treatment was generally well-tolerated and there were no new safety concerns.Reference...