Cerebrospinal fluid abnormalities in a phase III trial of Avonex (R) (IFN beta-1a) for relapsing multiple sclerosis

Background and objective: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo- controlled, double-blind, phase III clinical trial of IFN beta-Studies supp orted by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex(R), Biogen). The clinical trial demonstrated that TFN beta-1a treat ment resulted in significantly reduced disability progression, annual relap se rate, and new brain lesions visualized by cranial magnetic resonance ima ging. The objectives of the current study were to determine: (a) whether CS F abnormalities in MS patients correlated with disease or MRI characteristi cs, and (b) effects of IFN beta-1a therapy on these CSF abnormalities. Meth ods: CSF was analyzed from 262 (87%) of the 301 study subjects at entry int o the clinical trial, and a second CSF sample was analyzed from 137 of thes e 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), Ige index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse tate, gadolinium enhancemen t, and EDSS change according to baseline CSF status was used to determine t he predictive value of CSF for subsequent clinical and MRT disease activity . Change in CSF parameters after 104 weeks were used to determine the effec ts of treatment. Results: (1) At study baseline, 37% of the subjects had ab normal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chai ns, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) B aseline IgG index, kappa light chains, and OCB showed weakly positive, stat istically significant correlations with Gd-enhanced lesion volume and T2, l esion volume. WBC showed a statistically significant correlation with Gd-en hancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical an d MRT disease activity in placebo recipients. (4) IFN beta-1a treatment res ulted in significantly reduced CSF WBC counts, but there was no treatment-r elated change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. Conclusions: The curren t study documents significant reductions in CSF WBC counts in patients trea ted with IFN beta-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-tre ated relapsing MS patients. (C) 1999 Elsevier Science B.V. All rights reser ved.