onabotulinumtoxinA Injections Research Articles

The First Injection: Rates of Urinary Retention in Women With Urgency Incontinence Treated With Intravesical OnabotulinumtoxinA Injection.

The aim of the study was to describe the rate of symptomatic and asymptomatic urinary retention and catheterization in women undergoing initial intravesical onabotulinumtoxinA (BnTA) injection for urgency urinary incontinence (UUI). This retrospective chart review included women receiving initial 100 U of BnTA injection for UUI for 5 years. Straight-catheterized postvoid residuals (PVRs) were performed 2 weeks after the injection. Women without the sensation of incomplete bladder emptying, worsened urgency, inability to void, or suprapubic pain but with PVR of greater than 300 mL were characterized as having asymptomatic retention, whereas women with a PVR of greater than 150 and any of these symptoms were diagnosed with symptomatic retention. One hundred eighty-seven 187 patients received initial BnTA injection. The majority were postmenopausal (89%) and white (82%) with a mean age of 65 years and body mass index of 30 kg/m2. One-third of the cohort underwent baseline urodynamic studies. At 2 weeks after injection, 163 patients (87%) followed up, and 17 (10%) had either asymptomatic or symptomatic retention (2% and 8%, respectively). There were no differences in demographic or pretreatment urodynamic parameters in women with and without retention except that women who had previous anti-stress urinary incontinence procedures were more likely to experience retention (53% vs 18%, P = 0.002) despite similar baseline PVRs. We demonstrated that the rate of retention requiring catheterization after 100 U BnTA may be as high as 10% although only 5% develop PVRs for 300 mL and only 2% have asymptomatic retention for 300 mL.

OnabotulinumtoxinA Injections for Patients with Chronic Migraine During the COVID-19 Pandemic

Headaches are among the top prevalent conditions that physicians encounter in their daily practice. Migraine headaches affect nearly15% of the United States population (approximately 45 million).‎‎1,‎2 Over 50% of all patients with migraine report significant or severe impairment and disability.2 Migraine is the leading cause of years lived with disability among patients between ages 15 and 49 years old – the most productive years.‎‎3 According to the World Health Organization headache report, up to 4% of the world’s population experience chronic migraine (headaches occurring on at least 15 days per month with at least 8 of these headaches meeting migraine criteria).‎‎‎4 Approximately, 65% of patients with episodic migraine and 75% of patients with chronic migraine have missed family events and activities in the past month due to migraine-related impairment.‎‎5 Migraine also significantly impacts work-related activities. It has been estimated that 11% of patients with chronic migraine have been missing at least 1 day of work per week in the past 2 weeks‎.‎‎6 Based on migraine attack frequency and related disability, headache experts suggest offering prophylactic treatment options to patients with four migraine attacks per month or more. ‎‎7 Nevertheless, it has been estimated that only 26-29% of patients continue to adhere to their prophylactic treatment regimen at 6 months and only 17-20% continue to use their oral preventive medications at 12 months. ‎8,‎9 OnabotulinumtoxinA injection is an established FDA-approved therapy for chronic migraine prevention.

Modifications to the PREEMPT Protocol for OnabotulinumtoxinA Injections for Chronic Migraine in Clinical Practice.

To assess the PREEMPT protocol modifications that have developed in clinical practice over time. The United States Food and Drug Administration approved the 155-unit fixed-dose, fixed-site PREEMPT protocol of onabotulinumtoxinA (BoNT-A) injections for migraine prevention 9 years ago. This is an anonymous survey with free text response options of Headache Medicine clinicians. Out of the 878 contacted Headache Medicine clinicians, 182 (20.7%) completed the survey. Of the 182 respondents, 141 (77.5%) reported that they did not always follow the PREEMPT protocol. Of the 182 respondents, 128 (70%) changed the number of injections, 115 (63%) changed the total units of BoNT-A injected, 105 (57.7%) altered the location of injection sites (58%); 101 (55.5%) do not aspirate to ensure the absence of blood return; 22 (12.1%) changed the dilution; and 4 (2.2%) added lidocaine. The main reported reasons for changes in number, dose, and location of injections included adapting to the patients' pain, anatomy, and preferences. The wide inter- and intra-personal variations in BoNT-A injections for chronic migraine prevention seen in this survey raise concerns about the standardization of the procedure and suggest that an advisory protocol containing more evidence and discussion of the reasoning behind the recommendations might be more helpful than the current prescriptive protocol.

Management of Patients with Overactive Bladder in Brazil: A Retrospective Observational Study Using Data From the Brazilian Public Health System.

IntroductionIn Brazil, current data on the use of healthcare resources to manage individuals with overactive bladder (OAB) are lacking. This study aimed to characterize contemporary treatment and the economic burden among patients with OAB managed under the Brazilian public health system (Sistema Único de Saúde [SUS]).MethodsPopulation-based data from January to December of 2015 were acquired from Brazil’s public health database. Adults at least 18 years of age with an ICD-10 diagnostic code for OAB within the period were included. Records of outpatient visits, hospitalizations, and onabotulinumtoxinA injections were used to calculate estimates of resource use and costs (in Brazilian reals [R$]) among those with OAB (frequency [%] and mean (standard deviation [SD]) as appropriate). Patient identifiers were not available, so a record linkage methodology was used to match medical encounters to individuals. Pharmacologic management of OAB was informed by government medication purchases available from the official Brazilian government databases.ResultsDuring 2015, 26,640 patients with OAB were identified. All cohort members had at least one outpatient visit and 15,349 (57.6%) were hospitalized. Of the study cohort, 10.0% visited a general practitioner (GP), 41.3% visited a specialist, and 52.0% visited other non-medical healthcare practitioners within the year. Mean (SD) healthcare costs among the study cohort totaled R$355 (R$866) per patient per year; and were R$291 (R$654), R$27 (R$130), R$27 (R$30), and R$11 (R$17) for hospitalizations, GP, specialist, and non-medical healthcare practitioner visits per patient per year, respectively. Regional analysis of reported government medication purchases suggested that access to OAB treatments is highly limited.ConclusionsHigh resource use and costs were estimated among patients with OAB managed within the SUS. These data provide a snapshot of the management of patients with OAB in Brazil, with the patients seeking treatment under SUS likely representing a more burdened subpopulation.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01318-w) contains supplementary material, which is available to authorized users.

Extracranial Injections of OnabotulinumtoxinA in Combination with Intravenous Injection of Atogepant Attenuates Activation and Sensitization of HT and WDR Neurons by CSD (4287)

Extracranial Injections of OnabotulinumtoxinA in Combination with Intravenous Injection of Atogepant Attenuates Activation and Sensitization of HT and WDR Neurons by CSD (4287)

PD24-07 PREDICTIVE FACTORS FOR A SUCCESSFUL TREATMENT OUTCOME OF INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR PATIENTS WITH INTERSTITIAL CYSTITIS/ BLADDER PAIN SYNDROME

INTRODUCTION AND OBJECTIVE:Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS have different pheno...

Abstract 85: A Randomized, Controlled, Split-Face Study Comparing The Onset Of Action Of Prabotulinumtoxin-A And Onabotulinumtoxin-A

Purpose: Neuromodulator injection is the most commonly performed cosmetic procedure worldwide. As new formulations of botulinum toxin type A become commercially available, generating data on the clinical comparability between products is important. Here, the author compared the onset of action of prabotulinumtoxinA (Pra-B) and onabotulinumtoxinA (Ona-B) in the treatment of forehead and lateral canthal rhytids. Methods: A randomized, controlled, split-face pilot study was conducted on 5 subjects with mild to severe forehead and lateral canthal rhytids. All subjects were administered Pra-B and Ona-B injections to the forehead and periorbital region in a randomized, split-face manner. Toxin preparation, units administered, injection sites, and assessment timing were controlled. Subjects were assessed at baseline (day 0) and post-treatment at days 1, 2, 3, 4, 5, 6, and 7 using a validated 5-point Wrinkle Severity Scale (WSS; 0 = no lines, 4 = very severe lines). Standardized videography of subjects at rest and at maximal contraction was obtained at days 0, 1, 2, 3, 4, 5, 6 and 7 or until scale stability was achieved. Subject- and investigator-assessed WSS scores were reported. Primary end point was response onset (the time to improve by ≥1 point on the WSS) as defined by investigator assessment at maximal contraction. Results: 5 subjects (3 women, 2 men) with a mean age of 46.2 years (range, 29-69 years) were treated. Baseline mean score at maximal contraction was 2.8 for forehead rhytids (range, 1-4) and 2.0 for lateral canthal rhytids (range, 1-3) as assessed by investigator. Mean time of onset when treating the frontalis was 3.4 days for Ona-B and 3.2 days for Pra-B. Mean time of onset when treating the orbicularis oculi was 3.0 days for Ona-B and 2.2 days for Pra-B. At the time of response onset, Ona-B demonstrated a mean improvement of 1.2 points (frontalis) and 1.2 points (orbicularis oculi). Pra-B demonstrated a mean improvement of 1.3 points (frontalis) and 1.0 points (orbicularis oculi). Conclusion: Preliminary results from this pilot study suggest comparable time of onset and efficacy when treating the frontalis and orbicularis oculi with onabotulinumtoxinA and prabotulinumtoxinA injection.

MP07-17 PELVIC FLOOR CHEMODENERVATION OFFERS BENEFIT TO PATIENTS UNDERGOING PHYSICAL THERAPY FOR HIGH TONE PELVIC FLOOR DYSFUNCTION

INTRODUCTION AND OBJECTIVE: Therapeutic options for the management of painful high-tone pelvic floor dysfunction (HTPFD) are limited. We sought to determine whether the addition of pelvic floor chemodenervation to an established regimen of pelvic floor physical therapy (PFPT) for HTPFD improves patients’ subjective outcomes. METHODS: Subjects were recruited from an FPMRS practice. Inclusion criteria included a 6 month history of PFPT-refractory HTPFD. Exclusion criteria included pregnancy or any contraindication to onabotulinumtoxinA (BTX-A) injection. Pelvic floor BTX-A injections were offered following a standard template at either 50, 100, or 150 units. Following injection, patients continued PFPT and were followed for 12 months. Patient reported outcome measures were assessed with visual analog scale (VAS) pain indices of non-menstrual pelvic pain and dyspareunia, Patient Global Impression of Severity (PGI-S), the Pelvic Floor Distress Inventory (PFDI), and the Female Sexual Function Index (FSFI). The Patient Global Impression of Improvement (PGI-I) was also assessed following intervention. Appropriate statistical analyses were used to compare changes in survey responses over time. RESULTS: Twenty patients were enrolled. Of these, 40, 25, and 35% underwent injection with 50, 100, and 150 u, respectively. The average age was 42.8 years (range: 22-78) and BMI was 24.7 (SD: 6.1), with 90% of the subjects being Caucasian and 55% tolerating vaginal penetration prior to BTX-A injection. PGI-S scores showed significant improvement at 2 weeks through 12 months (baseline: 3.01 vs. 2.0-2.1, p<0.01). VAS rated pelvic pain showed >50% improvement at all follow up points; peak improvement was at 3 months (baseline 4.9 vs. 1.6, p<0.01). VAS rated dyspareunia showed significant improvement at 3 through 12 months following injection (baseline: 6.9 vs 2.2-3.4, p<0.01), and PFDI scores showed significant improvement at 3 through 6 months following injection (baseline: 63.3 vs 26.5-27.8, p=0.038-0.045). No significant changes (favorable or unfavorable) were noted with FSFI results. No major adverse events were documented. CONCLUSIONS: The addition of pelvic floor BTX-A to a PFPT regimen is effective in significantly reducing HTPFD-related pelvic pain and dyspareunia while improving health-related quality of life. Peak efficacy was noted 3 months after injection, and no detriment was seen to existing urinary, defecatory, or other sex-related complaints. Further study is needed, but the addition of pelvic floor BTX-A injection appears to be a promising adjunctive treatment for this clinically-challenging condition. Source of Funding: SUFU Chemodenervation Grant

Evaluation of botulinum toxin effects in hemifacial spasm patients: correlation between clinical rating scales and high-speed video system measurements.

The purpose of this study was to compare the scores of two clinical rating scales and high-speed video system measurements obtained during spontaneous eyelid movements in hemifacial spasm (HFS) patients before and after treatment. Patients were evaluated before and 30days after receiving treatment with onabotulinumtoxinA injections. Using a high-speed video system, the eyelid movements were recorded bilaterally for 3min and the energy power generated by the upper eyelid during spontaneous eyelid movements was assessed before and after treatment. The scores of the Jankovic rating scale (JRS) and Hemifacial Spasm Grading System (HSGS) were also assessed before and after treatment. The authors studied 22 patients. Significant reduction in JRS and HSGS scores and in the energy generated by the upper eyelid was observed after treatment. A power spectrum of less than 23,000 was associated with JRS and HSGS scores less than 4 and 6.25, respectively and a power spectrum greater than or equal to 23,000 was associated with JRS and HSGS scores greater than or equal to 4 and 6.25, respectively (p < 0.0001 and p = 0.0025). Rating systems are easy to use, but they may exhibit limitations in sensitivity to assess differences between distinct disease patterns and between subtle differences in treatment responses. The high-speed video system permits a greater degree of accuracy, which allows for the assessment of differences in eyelid movement patterns and would permit better tailoring of treatment to patients. However, simpler devices employing this system would need to be developed, so that it could be used in clinical practice.

45: The first injection: Rates of urinary retention in women with urgency incontinence treated with intravesical onabotulinumtoxinA (Botox) injection

To describe rate and risks for symptomatic and asymptomatic urinary retention requiring catheterization in women undergoing initial intravesical onabotulinumtoxinA (Botox) injection for urgency urinary incontinence (UUI). This was a retrospective chart review of women receiving their first 100 unit Botox injection for idiopathic UUI over 5-years. All patients had straight-catheterized post-void residual (PVR) done 2-weeks after injection. Based on symptoms and PVR patients were divided into “retention” and “non-retention” groups. The “retention” group was further divided into asymptomatic patients with a PVR greater than 300 mL or symptomatic patients with a PVR greater than 150 mL. Symptoms of retention included a sensation of incomplete bladder emptying, worsened urgency or frequency, difficulty/inability to void, or suprapubic pain. Continuous variables were compared using student t tests and categorical variables using χ2 tests. 187 patients with mean age of 65 ± 12 years and BMI of 29.7 ± 7.5kg/m2 were included. Majority was postmenopausal (89%) and white (82%). 69 underwent urodynamic testing (UDS) with 50% demonstrating DO. Mean baseline PVR was 27±30 ml. 163 patients (87%) followed up at 2-weeks. 17 (10%) had retention requiring catheterization: 4 were asymptomatic (PVR >300 mL) and 13 were symptomatic (9 with PVR >150 and <300ml and 4 with PVR >300 ml. Most (13 patients) elected to manage retention with intermittent straight catheterization and 1 with Foley. Three declined to have any catheterization. 20% had a symptomatic, culture-proven UTI in the first month after injection: 35% with and 19% without retention (p=0.09). There were no differences in maximum cystometric capacity (359±150 ml vs 321±105 ml, p= 0.64, baseline PVR (25±27ml vs 46±52 ml, p=0.12) or presence of DO (57% vs 29%, p = 0.16) in women with and without retention. Age (p=0.58), menopausal status (p=1.0), diabetes (p=1.0), and smoking (p=0.16) were not associated with retention. However, women who had previous anti-SUI procedures were more likely to experience retention (53% vs 18%, p = 0.002) even though they did not have higher baseline PVRs (32 vs 26ml, p=0.3). One in 10 women experienced clinically significant urinary retention within 2-weeks of initial Botox for UUI. Nearly all (98%) were symptomatic suggesting that routine PVR follow-up is unnecessary.

82: Effectiveness of reduced site injection protocol of intra-detrusor onabotulinumtoxin A

To examine the effectiveness and patient satisfaction associated with the use of a 5-site intra-detrusor injection protocol of onabotulinumtoxin A among women with urgency urinary incontinence. We performed a prospective cohort study of women undergoing intra-detrusor injection of onabotulinumtoxinA (Botox) for treatment of refractory urgency urinary incontinence (UUI) from 11/1/18 to 6/1/19. A 5-site injection protocol using 100 units (U) Botox was performed as opposed to the standard 10-20 injection site protocol. Women were included if they underwent the 5-site injection protocol and completed pre-treatment (baseline), 2-week post-treatment, and 3-month post-treatment voiding diaries and questionnaires. Demographic data, rates of post-procedure voiding dysfunction and urinary tract infection were collected. Three-day voiding diaries were collected at baseline, 2 weeks and 3 months post-procedure. The primary outcome was number of UUI episodes/day at 3 months. Each set of questionnaires consisted of the Incontinence Impact Questionnaire short version (IIQ-7) and Urogenital Distress Inventory short form (UDI-6) at baseline, 2 weeks post-procedure and 3 months post-procedure, as well as the Patient Global Impression of Improvement (PGI-I) at 2 weeks and 3 months. We compared baseline UUI episodes/day and questionnaire scores with matching parameters at 3 months using the Wilcoxon rank-sum test. A total of 19 women met inclusion criteria during the study period. The median age was 68 years [interquartile range, IQR 57-72], median BMI was 33 kg/m2 [IQR 28.3-36]. Sixteen (84.2%) patients identified as white, while 2 (10.5%) were black. Sixteen patients (84.2%) were menopausal, and 6 (31.6%) were diabetic. There was a statistically significant decrease in the median number of UUI episodes per day from baseline (median 4 [IQR 3-10.5]) to 3 months post-procedure (median 1 [IQR 0-2], p=0.007). There was also a statistically significant improvement in IIQ-7 scores from baseline (median 9 [IQR 7-15]) to 3 months post-procedure (median 3 [IQR 1-9], p=0.001). There was no difference in UDI-6 scores from baseline (median 7 [IQR 5-10]) to 3 months (median 5 [IQR 2-8], p=0.307). Five patients (26.3%) had post-procedure voiding dysfunction, while 2 (10.5%) had a post-procedure urinary tract infection. Fifteen patients (79%) reported symptoms were at least a little better based on the PGI-I at 2 weeks and at 3 months. A 5-site injection protocol of intradetrusor Botox resulted in statistically significant improvements in UUI episodes/day and quality of life at 3 months compared to baseline. These findings suggest that 5 injections are comparable to 10-20 in terms of published outcomes and complications.

106: Pelvic floor symptoms following onabotulinumtoxinA trigger point injections for myofascial pelvic pain: Analysis of secondary outcomes

Myofascial pelvic pain is a complex condition that is often associated with other pelvic floor symptoms. While pelvic floor physical therapy is considered first line therapy, pelvic floor injection of onabotulinumtoxinA is usually reserved for refractory myofascial pain. We set out to determine the effect of onabotulinumtoxinA point injections on pelvic floor symptoms compared to placebo. A double-blind, randomized, placebo-controlled trial in women with myofascial pelvic pain was conducted at a single institution. Participants were randomly allocated to a pelvic floor injection of 200 units of onabotulinumtoxinA or 20 mL of saline. All participants started 8 weeks of pelvic floor physical therapy at 4 weeks. Participants followed up at 2, 4, and 12 weeks after injection for assessment of pain. In addition to validated questionnaires, data was collected on presence of specific pelvic floor symptoms, including constipation, pain with defecation, dyspareunia, and dysmenorrhea. At each follow up, subjects indicated whether each symptom was present, and designated it as new, better, same or worse compared to the previous visit. Among subjects who were symptomatic at baseline, symptoms categorized as none or better were considered improved, whereas symptoms categorized as unchanged or worse were considered not improved. Sixty women were enrolled and randomized. One participant in the placebo group was lost to follow-up. Of the 59 subjects, 39 (66%) reported constipation, 28 (48%) reported pain with defecation, 35 (59%) reported dyspareunia, and 21 (36%) reported dysmenorrhea at baseline. Among subjects with constipation, 27% of intervention and 34% of control group reported improvement at 12 weeks. Among subjects with pain with defecation, 23% of intervention and 28% of control group reported improvement. Among subjects with dyspareunia, 27% of intervention and 17% of control group reported improvement. Lastly, among subjects with dysmenorrhea, 13% of intervention and 10% of control group reported improvement at 12 weeks. In our study, participants who received onobotulinumA experienced overall similar responses as placebo in specific pain symptoms from baseline to 12 weeks. There may be a trend toward improvement in dyspareunia but the number of subjects was too small. Pelvic floor physical therapy, which is considered to be first line therapy for myofascial pain, may help regardless of intervention. Our findings suggest that onabotulinumtoxinA should be reserved for women with myofascial pain with symptoms that have not previously responded to physical therapy. Future studies should evaluate other factors such as duration of pain, comorbidities and other pain conditions as factors in response to therapy.

Efficacy and tolerance of botulinum toxin injections after sacral nerve stimulation failure for idiopathic overactive bladder.

Management of idiopathic overactive bladder (iOAB) after the failure of sacral nerve modulation (SNM) is very challenging. To the best of our knowledge, no study has evaluated the use of botulinum toxin A (BoNT-A) after SNM failure for iOAB. The aim of this study is to evaluate the tolerance and efficacy of BoNT-A injection after the failure of SNM for iOAB. We conducted a retrospective multicentric analysis of all patients who had received either onabotulinumtoxinA or abobotulinumtoxinA intradetrusor injection for iOAB after SNM failure, between January 2004 and December 2017. The primary outcome was the percentage of success of first BoNT-A injection (either resolution of their urinary incontinence or their frequency or more than 50% reduction in frequency). Secondary outcomes were results of urodynamic studies, complications, total number of injections, causes of withdrawal, and subsequent treatment. Seventy-six patients (62 female) were included. The percentage of success of first BoNT-A injection was 43.4% (n = 33). All overactive bladder symptoms were significantly improved on the 3-day bladder diary. Twenty-eight patients (36.8%) were put under clean intermittent self-catheterization transitory. After a mean follow-up of 57.7 (±38.5) months, median number of injections was 2 (1-15). Overall, 42 patients (55.2%) stopped injections during follow-up. The estimated 36-months discontinuation-free rate was 48.1%. Mean cause of discontinuation was a primary failure (n = 32; 42.1%). BoNT-A can be used in SNM nonresponders with a success rate of 43.4% but is associated with a high long-term discontinuation rate.

Optimization of the rat digit abduction score (DAS) assay: Evaluation of botulinum neurotoxin activity in the gastrocnemius lateralis, peronei, and extensor digitorum longus.

The mouse digit abduction score (DAS) assay is commonly used to measure muscle flaccidity-inducing effects of botulinum neurotoxin (BoNT) in vivo. Adapting the assay to rats has been challenging, as injection of onabotulinumtoxinA (onaBoNT-A) into the gastrocnemius muscle, as performed in mice, or into the tibialis anterior leads to sub-optimal sensitivity of the test (Broide et al., 2013). To optimize the experimental design of the rat DAS assay, we evaluated the effects of research-grade, purified, native BoNT serotype A1 (BoNT-A) in three muscles: the gastrocnemius lateralis, peronei, and extensor digitorum longus using female animals. Following injection, animals were tested daily for the digit abduction and body weight.BoNT-A caused dose-dependent inhibition of digit abduction when injected into the gastrocnemius lateralis or peronei. BoNT-A was six-fold more potent when injected into the peronei in comparison to the gastrocnemius lateralis. As injection of BoNT-A into the extensor digitorum longus muscle resulted in an all-or-none digit abduction response and therefore prevented calculation of the ED50, it was considered unsuitable for the rat DAS assay. At equipotent doses, peronei- and extensor digitorum longus-injected animals showed normal body weight gain, while those injected with BoNT-A into the gastrocnemius lateralis gained less weight in comparison to vehicle-treated controls.Thus, injecting the peronei muscles of female rats offers optimized conditions for evaluating the biological properties of BoNTs in the rat DAS assay; for assessing the potency, onset, and duration of action across natural and recombinant BoNT in a robust and reproducible manner.

Efficacy and Safety of OnabotulinumtoxinA 400 Units in Patients with Post-Stroke Upper Limb Spasticity: Final Report of a Randomized, Double-Blind, Placebo-Controlled Trial with an Open-Label Extension Phase.

In many countries, 400 units (U) is the maximum dose of onabotulinumtoxinA available to treat upper limb spasticity, but few studies have demonstrated the optimal use of this dose. In the double-blind phase of this randomized, controlled trial, we compared the efficacy and safety of 400 vs. 240 U onabotulinumtoxinA in patients with post-stroke upper limb spasticity. Both groups received 240 U onabotulinumtoxinA injected in the forearm. An additional 160 U onabotulinumtoxinA (400 U group) or placebo (240 U group) was injected in the elbow flexors. Both groups showed similar muscle tone reduction in the wrist, fingers, and thumb; muscle tone reduction in the elbow flexors was greater in the group treated with onabotulinumtoxinA (400 U group) compared to placebo (240 U group). Functional disabilities improved in both groups. No substantial difference was found in safety profiles. In the subsequent open-label phase, all participants received repeat injections of 400 U onabotulinumtoxinA (target muscles and doses per muscle determined by the physician). Similar efficacy and safety outcomes, as with the 400 U group in the double-blind phase, were confirmed. This final report demonstrates that injection of onabotulinumtoxinA 400 U relieves muscle tone in a wide range of areas and improves functional disabilities; generally, it was well-tolerated, and no new safety concerns were identified. The dosing data in the open-label phase will inform optimal use of onabotulinumtoxinA in clinical practice (ClinicalTrials.gov: NCT03261167).

OnabotulinumtoxinA injection in the treatment of chronic migraine.

The earliest descriptions of botulism were in the early 19th century, and was reported by the German physician Justinus Kerner. The term "botulism" was derived from the Latin word botulus, indicating its original association with sausages. It took another 150 years or so to come into clinical use. The first clinical application was strabismus, and was developed by the American ophthalmologist Alan B. Scott, whose effort led to the pharmaceutical product known as onabotulinumtoxinA today. The therapeutic benefit in migraine was an incidental finding in a report by the American plastic surgeon William J. Binder, which inspired a series of clinical studies in headache disorders. The doses and injection techniques in the earlier reports were variable, so were the results. It was until the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) 1 and 2 studies when its efficacy and safety, as well as the indication, i.e., chronic migraine (CM), were ascertained. Even though there were criticisms regarding the heterogeneities in the results between the PREEMPT 1 and 2 studies, the data on efficacy endpoints and safety were generally consistent, which were subsequently confirmed by the open-label extension of the PREEMPT 1 and 2 studies, and three open-label studies, namely the Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL), the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilization, and Patient-reported OutcomeS observed in practice (REPOSE) studies, and the CM Post-Authorization Safety Study (CM PASS) studies. On the other hand, the results were challenged by the Chronification and Reversibility of Migraine (CHARM) study, which involved CM patients with medication overuse. It was concluded that the clinical improvement was attributed to early withdrawal of the overused acute medications, rather than onabotulinumtoxinA injections. However, fundamental differences in the patient profile and methodology between the CHARM and PREEMPT studies existed, and cautious should be exercised when interpreting and comparing the results. According to the practical guidelines and reimbursement regulations in many countries, its use is limited to CM patients, and is reserved for those who fail at least 2-3 preventive medications, due to either lack of efficacy or intolerability. Cessation of treatment is recommended in patients who do not respond to 2-3 injection cycles, or in patients whose headache frequency has dropped to <10-15 days a month. Even in the era of calcitonin-gene-related peptide monoclonal antibodies, onabotulinumtoxinA injection remains a treatment option of reasonable cost-effectiveness in carefully selected patients.

Dyspareunia in women

Dyspareunia is recurrent or persistent pain with sexual intercourse that causes distress. It affects approximately 10% to 20% of U.S. women. Dyspareunia may be superficial, causing pain with attempted vaginal insertion, or deep. Women with sexual pain are at increased risk of sexual dysfunction, relationship distress, diminished quality of life, anxiety, and depression. Because discussing sexual issues may be uncomfortable, clinicians should create a safe and welcoming environment when taking a sexual history, where patients describe the characteristics of the pain (e.g., location, intensity, duration). Physical examination of the external genitalia includes visual inspection and sequential pressure with a cotton swab, assessing for focal erythema or pain. A single-digit vaginal examination may identify tender pelvic floor muscles, and a bimanual examination can assess for uterine retroversion and pelvic masses. Common diagnoses include vulvodynia, inadequate lubrication, vaginal atrophy, postpartum causes, pelvic floor dysfunction, endometriosis, and vaginismus. Treatment is focused on the cause and may include lubricants, pelvic floor physical therapy, topical analgesics, vaginal estrogen, cognitive behavior therapy, vaginal dilators, modified vestibulectomy, or onabotulinumtoxinA injections.

Exploratory Randomized Double-Blind Placebo-Controlled Trial of Botulinum Therapy on Grasp Release After Stroke (PrOMBiS)

Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = −0.44, 95% CI = −1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program.

Cost-Effectiveness of Sacral Neuromodulation versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: Results of the ROSETTA Randomized Trial.

Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years. Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Neurourological Management After Failed Intradetrusor OnabotulinumtoxinA Injections

There are more questions than answers in the explanation for failure of onabotulinumtoxinA injection. We need to define what criteria should be used to diagnose it, what local bladder, neurological, or possibly immune phenomena are responsible for it, and the best and safest way to proceed in these vulnerable patients. We propose a management algorithm that may be worth testing at each step in clinical trials.