A longitudinal 36 monthly imaging study on the effect of NAb in patients with multiple sclerosis

A.W. Chiu, M. Ehrmantraut, N. Richert, J. Ohayon, F. Cantor, J. Frank, H. McFarland, F. Bagnato (Bethesda, USA)

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The clinical impact of neutralizing antibodies (NAb) in Multiple Sclerosis (MS) patients undergoing therapy with interferon beta (IFNB) remains controversial. To address this issue, both cross-sectional and longitudinal studies should be performed in the same cohort of patients. To our knowledge, monthly longitudinal assessment of NAb and its effect in MS patients has yet to be examined.

Fifteen consecutive relapsing remitting MS patients were treated with IFNB-1b (250 micro g, subcutaneous, every other day) for 3 years. Patients were followed with monthly (6-month pretherapy phase [PTP] and 36-month therapy phase [TP]) magnetic resonance imaging (MRI) and clinical exams as well as bimonthly NAb evaluations. MRIs were performed on a 1.5 Tesla magnet.

T2-weighted spin echo (SE) and T1-W images SE before and within 15 minutes of a 0.1 mmol/kg injection of gadopentate dimeglumine were obtained at each session. NAb evaluation was performed using the Myxovirus-A protein inhibition assay. Patients with NAb titres >=1:20 in at least 2 consecutive samples were considered NAb+. The relationship between NAb and contrast-enhancing lesion (CEL) activity is presently analyzed.

Of the 15 patients enrolled, 5 developed NAb. Of those 5 NAb+ patients, 2 developed NAb activity at low (e.g. <= 1:47) and transient titres, present only for no more than 6 measurements. However, both patients had consistent CEL activity throughout the entire TP.

One of these patients progressed into secondary progressive MS. The remaining 3 patients exhibited NAb titres between 1:24 – 1:2703 during the first 2 years of therapy that was coincident with the presence of CELs.

Although all 3 patients showed waxing and waning of NAb activity throughout TP, the NAb activity of 1 patient waned completely by month 19 while the NAb titre of the remaining 2 patients only began to decrease at month 20. CEL levels were concomitant with NAb titres in the former patient whereas CEL activity remained high in the latter 2 individuals. Notably, CEL activity was high in all three patients prior to the occurrence of NAb.

While our cohort is small, the length of the longitudinal follow-up offers a unique dataset worthy of description. While reduction in therapeutic efficacy is observed in patients with high NAb titres, those patients seem to exhibit a predisposition to poor IFNB-1b response prior to NAb occurrence. Further analyses in larger sample populations are warranted to confirm our preliminary investigation.