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Rate of brain atrophy in relapsing MS decreases during treatment with IFNß-1a

From the MS MRI Evaluation Centre Basel (Drs. Hardmeier, Freitag, Radue, and Kappos) and Departments of Neurology (Drs. Hardmeier and Kappos) and Neuroradiology (Dr. Radue), University Hospitals Basel, Switzerland; Institute for Medical Statistics and Epidemiology (Dr. Wagenpfeil), Klinikum rechts der Isar, Technical University, Munich, Germany; Cleveland Clinic Foundation (Drs. Fisher and Rudick), Cleveland, OH, and Biogen Idec (Dr. Kooijmans), Cambridge, MA; and Hôpital Purpan (Dr. Clanet), Toulouse, France.

Address correspondence and reprint requests to Dr. L. Kappos, Outpatient Clinics Neurology and Neurosurgery, University Hospitals Basel, Petersgraben 4, 4031 Basel, Switzerland; e-mail: lkappos{at}uhbs.ch

Objective: To determine the time course of brain atrophy during treatment with once-weekly IM interferon ß-1a (IFNß-1a).

Methods: The MRI cohort (n = 386) of the European IFNß-1a dose comparison study in relapsing multiple sclerosis (MS) was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, and volume of Gd-enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated.

Results: BPF decrease was –0.686% (first year), –0.377% (second year), and –0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first-year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (–1.06%) was significantly higher than the under-treatment rate (–0.33%).

Conclusions: In the first year of treatment with anti-inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon ß-1a and was sustained over the 3-year study period.

*See the Appendix on page 240 for a list of Group members.

The European IFNß-1a Dose Comparison Study in Relapsing MS was supported by Biogen Idec. Drs. Fisher, Rudick, Clanet, Radue, and Kappos have received grant support for their institutions for participation in clinical trials by Biogen Idec and other companies involved in the development of drugs for the treatment of multiple sclerosis. Dr. Kooijmans is an employee and owns stocks of Biogen Idec. Dr. Kappos is supported by the Swiss MS Society.

Dr. Freitag’s current address is Regionalspital Emmental, Department of Radiology, Burgdorf, Switzerland.

Received May 14, 2004. Accepted in final form September 8, 2004.

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