Interferon beta-1a (IFNß-1a) is currently given by intramuscular injection for the prevention of relapses and delay in accumulation of disability in the relapsing/remitting form of multiple sclerosis. Inhalation might be a useful alternative route of administration of IFNß-1a.

We investigated the safety of inhaled IFNß-1a, formulated as a dry powder with sucrose and leucine, in a randomised, double- blind, parallel group study. 21 healthy male and female volunteers, aged 18–44 years, were enrolled in the study and were scheduled to receive 4 doses of IFNß-1a (300 µg), excipient, or air (as a control), by inhalation at weekly intervals. 7 subjects were to receive each treatment. Safety was assessed by carbon monoxide transfer factor corrected for haemoglobin (TLCOc )¹, spirometry and pulse oximetry. TLCOc was measured on 2 occasions before the start of the study and the mean was taken as the baseline. TLCOc was measured at 48 and 144 h after each dose; the mean of those 2 readings was used as the post-dose value. Results were expressed as % of the subject’s predicted value. Any subject who had reduction of >15 in % predicted TLCOc post-dose compared with baseline (% predicted post-dose – % predicted pre-dose) was not dosed further, but continued with the scheduled TLCOc measurements.

Inhaled IFNß-1a significantly reduced TLCOc, after the third and fourth doses compared with air and after the second, third and fourth doses compared with excipient. The mean change in % predicted TLCOc from baseline is shown in Table 1.

Table 1: Mean (SD) change in % predicted TLCOc post-dose compared with predose

(n=7 per treatment *n=6)

Dosing was stopped in 3 subjects: 1 on each treatment. Dosing was stopped in 1 subject after 2 doses of IFNß-1a because of change in % predicted TLCOc of: ­–8 after dose 1, –16 after dose 2 (recovering to –14 after scheduled dose 3, and –10 after scheduled dose 4). Dosing was stopped in 1 subject after 2 doses of ‘air’ because of change in % predicted TLCOc of: –6 after dose 1, –16 after dose 2 (then –3 after scheduled dose 3, and –2 after scheduled dose 4). Dosing was stopped in 1 subject after 1 dose of excipient owing to a persistent cough, without reduction in TLCOc. In addition, 1 subject withdrew a 4 th subject withdrew from the study after 3 doses of excipient, and another after 3 doses of IFNß-1a, for reasons unrelated to the study. Data from these 5 4 subjects are included in Table 1. The reductions in TLCOc were reversible. There were no important changes in spirometry or pulse oximetry.

In conclusion, inhaled IFNß-1a reduced TLCOc, whereas the sucrose/leucine excipient did not. Therefore , repea t ed doses of IFNß-1a cannot safely be given by inhalation.

Am J Resp Crit Care Med 1995; 152: 2185–2198.