Based largely on old retrospective reports, the recommendation of injecting BoNT as infrequently as possible, with the lowest possible dose, was formed. While BoNT is inherently immunogenic, with improved production, most patients no longer develop immune resistance and poor response to BoNT is often due to other factors.
In a randomized controlled trial (RCT) using abobotulinumtoxinA for cervical dystonia (CD) by the German Dystonia Study Group, half of the patients treated with 250 and 500 U, and 39% in the 1000 U group required retreatment after 8 weeks. In a RCT comparing onabotulinumtoxinA and incobotulinumtoxinA for CD by Benecke et al., waning of effect was noted in 70 days for both toxins. Finally, two long-term prospective trials employing flexible intervals, with reinjections based on patient's request, have been performed using incobotulinumtoxinA. In the CD study, 22.5% were re-injected in <10 weeks and 24.6% between 10 and 12 weeks. In the blepharospasm study, the median injection interval was 6–10 weeks for 23.7% and 10–12 weeks for 32.3%)
While long-term studies utilizing flexible/shortened intervals, with vigilance over immunogenicity are needed, the majority of current evidence no longer support the very stringent adherence to strict 90-day BoNT injection intervals.