1
in vitro studies have also found that approximately one-third of patients treated with BTX-A demonstrate cross-reactive antibodies against BTX-B despite never having been treated with BTX-B (ref- erence 3 in article). 1 If these in vitro studies are clinically significant, it may mean that some patients with antibodies to BTX-A may also be nonresponsive to BTX-B or may not respond after only a few injections. Thus, it is important for urologists to minimize the po- tential for antibody formation to preserve long-term clinical respon- siveness to BTX. What are the clinical implications of these 2 articles? If you inject botulinum toxin type A for the first time in a patient and the patient is no better, there is no justification to try type B. Either the chosen dose used was inadequate or the bladder problem will not respond to botulinum toxin. However, if you have successfully used botulinum toxin type A in a patient for several years and yet after the most recent injection the patient reports no improvement at all, this should make you suspect that resistance to botulinum toxin type A may have developed. Your option would be to consider trying type B. In conclusion, botulinum toxin is a novel and promising treatment for a variety of lower urinary tract dysfunctions. The published clinical results are impressive and I have found Botox to be safe and effective during a 6-year period. 2 However, since application of BTX in the lower urinary tract is not FDA approved at this time, caution should be used until prospective multicenter randomized studies are completed to assess the safety and efficacy of BTX in urological diseases. Michael B. Chancellor Department of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 1. Doellgast, G. J., Brown, J. E., Koufman, J. A. and Hatheway, C. L.: Sensitive assay for measurement of antibodies to Clos- tridium botulinum neurotoxins A, B, and E: use of hapten- labeled-antibody elution to isolate specific complexes. J Clin Microbiol, 35: 578, 1997 2. Phelan, M. W., Franks, M., Somogyi, G. T., Yokoyama, T., Fraser, M. O., Lavelle, J. P. et al: Botulinum toxin urethral sphincter injection to restore bladder emptying in men and women with voiding dysfunction. J Urol, 165: 1107, 2001 REPLY BY REITZ AND SCHURCH We confirm that botulinum toxin type B may be an option for patients with neurogenic detrusor overactivity who became resistant to the type A toxin after repeated injections. However, it must be noted that in animal models as in human experiments injection of type B toxin in striated muscles has been shown to have a shorter duration of action than the type A toxin, 1,2 which needs to be con- sidered when using the type B toxin. To our knowledge, almost nothing is known about the duration of action of botulinum toxin type B injection in smooth muscles and, therefore, further research is required. It should be clear that antibody production against type A toxin does not necessarily interfere with type B toxin. Furthermore, antibody production probably depends on the individual immune responsiveness and is considered to have no direct effect on clinical response to the treatment. 3 We believe that in patients with primary resistance to type A toxin, which we define as the absence of a clinical and urodynamic effect after injection of an adequate dose in the detrusor smooth muscle, use of type B toxin may be justified because both toxins interact with different target proteins, and a primary nonresponse to type A toxin does not necessarily imply a nonresponse to type B toxin. 1. Aoki, K. R.: A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice. Toxicon, 39: 1815, 2001 2. Matarasso, S. L.: Comparison of botulinum toxin types A and B: a bilateral and double-blind randomized evaluation in the treatment of canthal rhytides. Dermatol Surg, 29: 7, 2003 3. Siatkowski, R. M., Tyutyunikov, A., Biglan, A. W., Scalise, D., Genovese, C., Raikow, R. B. et al: Serum antibody production to botulinum A toxin. Ophthalmology, 100: 1861, 1993 BOTULINUM TOXIN TYPE B FOR NEUROGENIC DETRUSOR OVERACTIVITY 805

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in vitro studies have also found that approximately one-third ofpatients treated with BTX-A demonstrate cross-reactive antibodiesagainst BTX-B despite never having been treated with BTX-B (ref-erence 3 in article).1 If these in vitro studies are clinically significant,it may mean that some patients with antibodies to BTX-A may alsobe nonresponsive to BTX-B or may not respond after only a fewinjections. Thus, it is important for urologists to minimize the po-tential for antibody formation to preserve long-term clinical respon-siveness to BTX.

What are the clinical implications of these 2 articles? If you injectbotulinum toxin type A for the first time in a patient and the patientis no better, there is no justification to try type B. Either the chosendose used was inadequate or the bladder problem will not respond tobotulinum toxin. However, if you have successfully used botulinumtoxin type A in a patient for several years and yet after the mostrecent injection the patient reports no improvement at all, thisshould make you suspect that resistance to botulinum toxin type Amay have developed. Your option would be to consider trying type B.

In conclusion, botulinum toxin is a novel and promising treatmentfor a variety of lower urinary tract dysfunctions. The publishedclinical results are impressive and I have found Botox to be safe andeffective during a 6-year period.2 However, since application of BTXin the lower urinary tract is not FDA approved at this time, cautionshould be used until prospective multicenter randomized studies arecompleted to assess the safety and efficacy of BTX in urologicaldiseases.

Michael B. ChancellorDepartment of UrologyUniversity of Pittsburgh School of MedicinePittsburgh, Pennsylvania

1. Doellgast, G. J., Brown, J. E., Koufman, J. A. and Hatheway,C. L.: Sensitive assay for measurement of antibodies to Clos-tridium botulinum neurotoxins A, B, and E: use of hapten-labeled-antibody elution to isolate specific complexes. J ClinMicrobiol, 35: 578, 1997

2. Phelan, M. W., Franks, M., Somogyi, G. T., Yokoyama, T.,

Fraser, M. O., Lavelle, J. P. et al: Botulinum toxin urethralsphincter injection to restore bladder emptying in men andwomen with voiding dysfunction. J Urol, 165: 1107, 2001

REPLY BY REITZ AND SCHURCH

We confirm that botulinum toxin type B may be an option forpatients with neurogenic detrusor overactivity who became resistantto the type A toxin after repeated injections. However, it must benoted that in animal models as in human experiments injection oftype B toxin in striated muscles has been shown to have a shorterduration of action than the type A toxin,1,2 which needs to be con-sidered when using the type B toxin. To our knowledge, almostnothing is known about the duration of action of botulinum toxintype B injection in smooth muscles and, therefore, further research isrequired. It should be clear that antibody production against type Atoxin does not necessarily interfere with type B toxin. Furthermore,antibody production probably depends on the individual immuneresponsiveness and is considered to have no direct effect on clinicalresponse to the treatment.3

We believe that in patients with primary resistance to type Atoxin, which we define as the absence of a clinical and urodynamiceffect after injection of an adequate dose in the detrusor smoothmuscle, use of type B toxin may be justified because both toxinsinteract with different target proteins, and a primary nonresponse totype A toxin does not necessarily imply a nonresponse to type Btoxin.

1. Aoki, K. R.: A comparison of the safety margins of botulinumneurotoxin serotypes A, B, and F in mice. Toxicon, 39: 1815,2001

2. Matarasso, S. L.: Comparison of botulinum toxin types A and B:a bilateral and double-blind randomized evaluation in thetreatment of canthal rhytides. Dermatol Surg, 29: 7, 2003

3. Siatkowski, R. M., Tyutyunikov, A., Biglan, A. W., Scalise, D.,Genovese, C., Raikow, R. B. et al: Serum antibody productionto botulinum A toxin. Ophthalmology, 100: 1861, 1993

BOTULINUM TOXIN TYPE B FOR NEUROGENIC DETRUSOR OVERACTIVITY 805