Antibody-induced botulinum toxin therapy failure: can it be overcome by increased botulinum toxin doses?

In some patients treated with botulinum toxin type A (BT) therapy failure occurs due to the formation of antibodies against BT (BT-AB). We investigated whether increased BT doses can overcome this form of therapy failure. Eight patients with cervical dystonia, secondary BT therapy failure and evidence of BT-AB formation in the mouse diaphragm bioassay received BT test doses (Dysport, Ipsen Ltd., Maidenhead, Berks, UK) into one of their sternocleidomastoid muscles. Test doses were increased in three steps at 3-month intervals and their effect on the amplitude of the electromyographic activity of the sternocleidomastoid muscle under maximal isometric activation (M-EMG) was measured and compared to a control group. In step 1 (200 or 300 MU) the M-EMG reduction was 12 +/- 13% compared to 85 +/- 10% (200 MU) and 83 +/- 9% (300 MU) in the control group. In step 2 (400, 600 or 800 MU) the M-EMG reduction was 25 +/- 21% compared to 78 +/- 7% (400 MU) in the control group. In step 3 (1,600 or 1,800 MU) the M-EMG reduction was 24 plus minus 10%. Side effects were not observed in any of the patients studied. In 1 patient with partial secondary BT therapy failure, with a low BT-AB titre (0.0015 U/ml) and with a moderately pathological M-EMG reduction of 40% with 200 MU a normal M-EMG reduction of 71% could be regained with 800 MU. In three subsequent therapeutic injection series with quadrupled BT doses in all target muscles the original therapy outcome could be regained and maintained. Side effects or increasing BT-AB titres were not observed. Even massively increased BT doses cannot overcome BT-AB-induced complete secondary therapy failure. However, in patients with partial secondary therapy failure, low BT-AB titres and a moderately pathological M-EMG reduction, increased BT doses might regain and maintain normal BT efficacy without induction of side effects or increasing BT-AB titres.