Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity.

Abstract

Botulinum toxin (BT) can stimulate formation of BT antibodies (BTAB) thus producing Antibody-Induced Therapy Failure (ABTF). BTAB titres may drop eventually. When BT therapy is then re-started with conventional BT drugs, BTAB titres re-increase promptly. We wanted to study whether the use of the low-antigenicity BT drug incobotulinumtoxinA (INCO) can prevent this re-increase. 8 patients with cervical dystonia and ABTF with maximal BTAB titres (6 women, 2 men, age 41.4 ± 12.1years, disease duration 6.6 ± 4.7years) were studied. ABTF ocurred under onabotulinumtoxinA (ONA) in five patients and under abobotulinumtoxinA (ABO) in 3 after 8.8 ± 3.8 injection series and a treatment time of 962.0 ± 473.2days. After 3881.5 ± 2468.3days without BT, all BTAB titres had dropped to insignificant levels before BT therapy was re-started with INCO. Treatment parameters before and after re-start were as follows: single dose 219.2 ± 90.7MU vs 252.6 ± 109.0MU (ns), interinjection interval 119.7 ± 18.4 vs 104.5 ± 14.7 days (ns), cumulative dose 1893.8 ± 1161.6MU vs 5130.4 ± 3602.5MU (ns), treatment time 962.0 ± 505.9 vs 1895.4 ± 1211.4days (ns) and number of injection series 8.8 ± 3.8 vs 19.3 ± 11.8 (ns). Repeated BTAB measurements and clinical examinations did not reveal any signs of ABTF after re-start. INCO offers a new and long-term treatment opportunity for ABTF patients when their BTAB titres have dropped. Our observations also confirm lower antigenicity of INCO compared to conventional BT drugs.