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SUPPLEMENTAL DATA (Figure (E) F-1 description):

Figure (E)F-1.A-1.F: Longitudinal monthly brain MRI scans and neurological evaluations.

Patient MS.1 (Figure (E)F-1.A) experienced 1.9 exacerbations per year during the baseline. IFN-1b induced a reduction in the number of Gd-enhancing lesions (30.6 to 10.3). Elevated titers of NAB against IFN1b were detected during months 34 and 42 (1:24 and 1:20). Subsequently, the lesion frequency increased and the patient experienced four clinical exacerbations. While on IFN-1b and AZA combination therapy, he remained exacerbation-free and maintained a low (average 3.6) total number of Gd-enhancing lesions in spite of persistently high (average 131) NAB titers during the combination therapy.

Patient MS.2 (Figure (E)F-1.B) had 5.3 exacerbations per year at baseline. IFN-1b induced a prompt decrease in the number of Gd-enhancing lesions (from 10.0 to 4.5), while the patient continued to have frequent exacerbations (average 1.9 per year). After 13 months on the IFN-1b and AZA combination therapy, the patient experienced complete response with no exacerbations and Gd-enhancing lesions. Throughout the study, 18 consecutive measurements of NAB were negative.

Patient MS.3 (Figure (E)F-1.C) experienced three exacerbations preceded by sharp increases in the number of Gd-enhancing lesions at baseline. Treatment with IFN-1b maintained a low number of Gd-enhancing lesions over 12 months. After the initial response, NAB titers rose to 1:22, 1:42, and 1:79 at months 23, 24, and 27. Upon subsequent increase to 48 Gd-enhancing lesions per scan, oral AZA was introduced. During the combination therapy, the patient remained exacerbation-free with an average number of Gd-enhancing lesions 9.6 per scan.

Patient MS.4 (Figure (E)F-1.D) had an average of 36.4 Gd-enhancing lesions and two exacerbations at baseline. While treated with IFN-1b, she remained exacerbation-free with an elevated number of Gd-enhancing lesions (average 34.4). On AZA, she continued to be exacerbation-free, but had recurrent increases in the number of Gd-enhancing lesions (mean value 15.3). Five consecutive NAB measurements were negative.

Patient MS.5 (Figure (E)F-1.E) qualified as primary non-responder to IFN-1b, as there was no significant decrease in the number of Gd-enhancing lesions during IFN-1b treatment. Oral AZA induced a decrease in average number of Gd-enhancing lesions (6.0 to 4.4), yet no significant clinical response. During this treatment period, NABs were detected at titer 1:592.

In Patient MS.6 (Figure (E)F-1.F), IFN-1b did not induce a significant response; the patient maintained an average of 17 Gd-enhancing lesions per month. The relapse rate on monotherapy was not established because this patient had been treated with IFN-1b only for three months. AZA had a modest effect on the number of Gd-enhancing lesions and no significant effect on exacerbation rate.