Long-term Safety and Tolerability of Repeated Treatments With OnabotulinumtoxinA in Children With Neurogenic Detrusor Overactivity.

PURPOSE: OnabotulinumtoxinA is an approved treatment for neurogenic detrusor overactivity in adults inadequately managed with anticholinergics, and more recently was approved in children on the basis of a phase 3, 48-week, single-treatment study (NCT01852045). Given the paucity of long-term pediatric data, we report on the continued safety in these patients after repeated onabotulinumtoxinA treatment. MATERIALS AND METHODS: This was a multicenter, double-blind, repeat-treatment extension study (NCT01852058) in patients who entered from the preceding single-treatment study. Data were integrated across both studies. All patients (5-17 years) used clean intermittent catheterization and could receive dose escalations based on response to preceding treatment (50 U, 100 U, or 200 U onabotulinumtoxinA [not to exceed 6 U/kg]). RESULTS: Overall, 95, 90, 55, and 11 patients received 1, 2, 3, and 4 treatments with onabotulinumtoxinA, respectively, and median (quartiles) duration of follow-up was 82 (65, 94) weeks. The safety profile was similar across doses and after repeat treatments. The most common treatment-emergent adverse event during cycles 1, 2, and 3 was urinary tract infection (31%, 34%, 22%). Three serious treatment-emergent adverse events related to study treatment (3/95; 3.2%) were reported during the study, which were all cases of urinary tract infection. Annualized urinary tract infection rates post-treatment were similar to pre-screening rates. There were no cases of autonomic dysreflexia, neutralizing antibodies, and treatment-emergent adverse events related to distant spread of toxin. CONCLUSIONS: OnabotulinumtoxinA continued to be well tolerated after repeated treatments in pediatric neurogenic detrusor overactivity patients with similar safety profiles across dose groups. Treatment-emergent adverse events were primarily urological with no new safety concerns.

Hypersensitivity Reactions Following Onabotulinum Toxin A Touch-up Injection Possibly Associated with Covid-19 Infection.

As one of the most common cosmetic procedures, botulinum toxin A (BTX-A) injections are basically safe. The typical allergic reactions include erythema, edema, pruritus, and wheal, which generally occur at the initial injection. Herein, we reported two cases of hypersensitivity reactions following cosmetic BTX-A touch-up injection. Type I allergic reactions provoked by re-exposure to the excipients such as gelatin may play a role in the event. In addition, this condition may be associated with the preceding Covid-19 infection, even with complete symptoms remission and negative tests results. Noteworthily, one case developed anaphylactic symptoms resembling purpuric drug eruption (PDE). These cases may serve as a significant complement to the botulinum toxin treatment safety profiles. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chronic Migraine: A Narrative Review on the Use of Botulinum Toxin with Clinical Indications and Future Directions.

Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. The pathophysiology of CM is characterized by an abnormal activation of the trigemino-vascular system in the meninges causing a neurogenic inflammation, which explains the use of anti-inflammatory during attacks. It seems that the objective of the preventive therapy with the botulin toxin OnaBoNT-A consists in interrupting the release of CGRP and other neuropeptides as well as the activation of C-fiber nociceptor and of the nearby A-delta fibers. The protocol for migraine treatment with OnaBoNT-A injections consists of 31-39 pericranial injection sites involving seven muscle groups bilaterally in specific areas of the head and neck, with a total dose of between 155 and 195 units, every three months. The severe adverse events reported with high doses of botulin toxin for spasticity, have not been reported for CM treated with OnabotA at the labeled dose. The established improvement with onabotulinumtoxinA treatment in CM patients had a positive impact not only in reduction monthly headache days but also in improving quality of life, with reduction in both healthcare resource utilisation (HRU) and work impairment. Aim of this review was to give an overview on the use of BoNT-A in patients with CM, giving practical advices on the clinical indications.

A case of migraine treatment in a patient with a clinical diagnosis of CHARGE syndrome using onabotulinum toxin A.

CHARGE syndrome is a genetic disorder that affects multiple organ and sensory systems. Cranial nerve involvement is one of the key clinical diagnostic criteria. We present the case of an 8-year-old girl with CHARGE syndrome, associated right-sided facial palsy, and chronic severe migraines, that were intractable to medical treatment. At age 6, onabotulinum toxin A was used to weaken the contralateral non-paralyzed side of her face to address her stigmatizing asymmetry. Onabotulinum toxin A chemodenervation was performed on the left lower lip depressors to relax the muscles and improve left lower lip position. Coincidentally, it was noted that with these treatments, migraine symptoms resolved. As the chemodenervation subsided over the next 3-4 months, the severe migraines returned. Continued treatment with onabotulinum toxin A injections every 3 months has resulted in ongoing improvements in facial symmetry and migraine control. Onabotulinum toxin A is a well-known treatment of chronic migraine. Injections are usually directed to the occipitalis, frontalis, and corrugator muscles. The literature has no reports of injections to the lower lip depressors as a useful therapy for migraine, making the results from this case unique.

Comparison of preseptal and pretarsal onabotulinum toxin an injection in patients with hemifacial spasm.

AIM: The aim of the present study was to evaluate the effects of different doses of onabotulinum toxin A on the amplitude and latency values of the blink reflex and facial nerve in the pretarsal and preseptal portions of the orbicularis oculi muscle in patients with hemifacial spasm. MATERIALS AND METHODS: Thirty patients with hemifacial spasm were assigned in two equal groups: Pretarsal Group: Five units of onabotulinum toxin A were injected into each of 2 points of the pretarsal portion; Preseptal Group: Five units of onabotulinum toxin A was injected into 4 points of the preseptal portion. We compared the electromyographic features of the patients before and 5 weeks after botulinum toxin (BTX) injection. RESULTS: In comparison of pre- and post-treatment measurements of blink reflex amplitude responses, the decreases in R1 (p = 0.003), R2 (p < 0.001), and R2C amplitudes (p = 0.031) were found to be significant in the BTX injected side in the pretarsal group. In the comparison of pre- and post-treatment measurements of facial nerve compound action potential amplitude changes, decreases in the amplitudes of the BTX injected (ipsilateral), and uninjected (contralateral) side in the pretarsal group were found to be significant (p < 0.001 for both groups). Decreases in the amplitudes of the BTX injected, and uninjected side in the preseptal group were found to be significant (p < 0.001, and p = 0.008, respectively). CONCLUSION: According to our hypothesis, the smaller amount of BTX applied to the pretarsal portion was found to be more effective than higher amount of BTX injected into the preseptal portion of the orbicularis oculi muscle.

Effectiveness, Safety, and Health-Related Quality of Life of Chronic Migraine Patients Treated with Onabotulinum Toxin A.

OBJECTIVE: The present study aims to describe the efficacy and safety of onabotulinum toxin A (BonT-A) with evaluation of treatment satisfaction and impact on quality of life in chronic migraine (CM) patients in real life. METHODS: This study was conducted in CM patients who were treated with BoNT-A with 12 months of follow-up. Data about outcome, adverse events, and patients' pre- and post-treatment status including health-related quality of life data were analyzed. Health-related quality of life scores were measured at baseline and months 6 and 12 after the beginning of BoNT-A administration. RESULTS: Of 42 enrolled patients, 30 were included in the analysis. At 12 months, all patients showed a reduction in number of headaches and analgesic use per month and none reported adverse events. After BoNT-A supplementation, health-related quality-of-life scores improved significantly. There was a direct association between health-related quality of life with reduction of headache days at the end of study. CONCLUSION: This study confirms that BoNT-A treatment is effective on CM and improves the functional well-being and quality of life of patients.

[Modern migraine therapy-interdisciplinary long-term care]. / Moderne Migränetherapie ­ fachübergreifende Versorgung im Langzeitverlauf.

Migraine has a very high lifetime prevalence with a severe illness-related burden. As a result, extensive long-term and regular treatment is required, which cannot be covered solely by neurologists. This is particularly the case for the long-term monitoring of migraine, which often takes place over several decades. The diagnosis is made using the diagnostic criteria of the International Headache Society (ICHD-3) based on the clinical phenotype. Owing to often complex neurological symptoms, a detailed weighing up of the differential diagnoses is required, which calls for specialist neurological expertise. The same is true for follow-up appointments of more complex therapy issues. Acute therapy with antiemetics, analgesics, and triptans can, so long as it is effective and is administered not longer than 10 days per month, be carried out by the general practitioner or specialist in internal medicine. This is also true for medical prophylactic treatment with dietary supplements, antihypertensive drugs, and tricyclic antidepressants. If this therapy is unsuccessful, prophylactic substances must be used that require more specialized knowledge, which is also reflected in the formal prescription requirements. Neurologists and pain therapists should then be involved in the treatment. This is particularly true for the use of Onabotulinumtoxin A and monoclonal CGRP-(receptor)-antibodies.

The Treatment of Facial Asymmetry with Botulinum Toxin: Current Concepts, Guidelines, and Future Trends.

This article will describe facial asymmetry secondary to facial nerve paralysis (FNP), and review current concepts, guidelines, and future trends. Despite the increasing use of botulinum toxin (BoNTA) in treating FNP, ideal dosage, timing, and additional therapies are not unequivocally established. Facial asymmetry significantly impacts quality of life (QOL) by strongly affecting self-perception and social interactions; injectables may mediate great clinical improvement. This article provides practical guidelines for the use of BoNTA and provides schemes for accurate assessment and documentation. A systematic, stepwise approach is recommended with methodical assessment, meticulous placement, conservative dosage, and careful follow-up. Future trends include the potential use of newly developed toxins, muscle modification with fillers, improved imaging techniques, and targeted QOL studies. Hopefully, a growing number of aesthetic injectors may become technically proficient and join multidisciplinary teams for managing FNP.

Randomized controlled trial of belladonna and opiate suppository during intravesical onabotulinum toxin A injection.

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.

Efficacy of onabotulinum toxin A injection in pediatric patients with non-neurogenic detrusor overactivity.

AIMS: To evaluate the effectiveness and reliability of onabotulinum toxin A (onaBoNT-A) injections in pediatric patients with non-neurogenic detrusor overactivity (NNDO). METHODS: Between January 2010 and February 2016, 39 patients underwent onaBoNT-A injections for NNDO, and were evaluated retrospectively. Three-day voiding diary was filled at baseline, and at the postoperative 9th month. The voiding frequency, incontinence episodes, and the cystometric capacity were noted. Vesicoureteral reflux (VUR) associated with NNDO, and presence of nocturia were recorded. Additional injection requirements were also stated. RESULTS: We reached the data of 33 patients on 9th month. The mean age was determined as 8.75 ± 3.01 (5-16) years. Initially, the mean bladder capacity was calculated as 114.66 ± 35.23 mL on the voiding diary, and 153.15 ± 47.40 mL on the baseline urodynamic study. After the procedures, the mean bladder capacity increased to 140.84 ± 45.61 mL (P = 0.0011), the mean daily voiding frequency decreased from 10.36 ± 1.05 to 7.42 ± 0.83 (P = 0.01), and the mean incontinence episodes decreased from 2.72 ± 1.87 to 1.18 ± 1.13 (P = 0.001), on voiding diary. VUR associated with NNDO was determined in 10 (30.3%) patients. The degree of VUR decreased three in patients, and VUR disappeared in five patients following the injections (P = 0.011). Fourteen (42.4%) patients had nocturia, and after the injections, nocturia disappeared in five (15.15%) patients (P = 0.151). Additional injections were required in 10 (30.3%) patients at the 9th month. CONCLUSIONS: OnaBoNT-A injections can be used in the pediatric patients with NNDO as an effective and reliable procedure by decreasing voiding frequency, incontinence episodes, and increasing bladder capacity, with negligible side effects and complications.

Action mechanisms of Onabotulinum toxin-A: hints for selection of eligible patients.

In the past few decades, the so-feared botulinum toxin has conversely acquired the role of a ever more versatile therapeutic substance, used in an increasing number of pathological situations, including chronic headache and more precisely in the prophylaxis of chronic migraine. The medical use of botulinum toxin allowed to better understand its multiple mechanisms of action. Investigations about the pathophysiology of primary and secondary headaches has shown a series of common biological elements that frequently are also targets of the action of botulinum toxin. These increasing evidences allowed to identify some biochemical, neurophysiological and radiological markers that may be useful in the individuation of patients which probably will respond to the treatment with Onabotulinum toxin-A among chronic migraineurs. These predictors include CGRP plasmatic levels, specific laser-evoked potential responses, peculiar brain MRI and fMRI and characteristic clinical manifestations. Unfortunately, at now, these predictors are still not available for the clinical practice. Furthermore, the better knowledge about biology of headaches and regarding botulinum toxin activities may also help in directing investigations on the possible use of Onabotulinum toxin-A in other headaches different from migraine. This review tries to show in detail these biological mechanisms and their implication in selecting patients eligible for the treatment with Onabotulinum toxin-A.

The use of onabotulinum toxin A (Botox(®)) in the treatment of chronic migraine at the Parma Headache Centre: a prospective observational study.

Chronic migraine is a debilitating headache, whose treatment is often complicated by the concomitant overuse of symptomatic medication and by the poor efficacy of standard prophylactic treatments. The PREEMPT studies have demonstrated the efficacy and tolerability of onabotulinum toxin A (Botox(®)) in the treatment of this headache type. Data about its use in clinical practice are still scarce. Our study evaluated all subjects with chronic migraine who were treated with onabotulinum toxin A between February 2014 and November 2015 at the Parma Headache Centre. Botox was injected according to the PREEMPT paradigm every 3 months. The data about variations in the number of headache days and in symptomatic medication intake before and after the Botox injections were collected from the patients' headache diaries. The study also evaluated tolerability to treatment, disability, and depressive symptoms. Of the 52 treated subjects, 14 received Botox treatment for at least 9 months and showed a significant decrease in the median number of headache days (from 19 to 14.5, p = 0.011) and in the median number of days of symptomatic medications intake and symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS and BDI-II scores after 9 months were reduced, though not significantly. The treatment with Botox proved effective and well tolerated in our clinical practice. Further studies on larger patient samples will help shed light on the persistence of the drug's effect at long term and identify the predictive factors of response to treatment.

Prophylactic Drug Treatment of Migraine in Children and Adolescents: An Update.

Migraine as a highly disabling pain condition influences the daily activities of those affected, including children and adolescents. The pathomechanism of migraine is not fully understood, and the different types of prophylactic antimigraine drugs that are applied are not specific for migraine. There is a need for preventive treatment in the event of frequent migraine attacks, an impairment of the quality of life, severe accompanying or aura symptoms, and the failure of acute drug treatment. The following pharmacological classes are recommended: antidepressants, antiepileptics, antihistamines, beta-adrenergic receptor blockers, and calcium ion channel antagonists, besides onabotulinum toxin A and nutraceuticals (butterbur). The most urgent goal as concerns pharmaceutical innovation is the development of pathomechanism-based antimigraine drugs and personalized therapy tailored to the children and adolescents.

[Patient information before bladder wall injection of botulinum toxin A (Botox®): Which essential items? Results of Delphi consensus from GENULF experts]. / Information patient avant injection de toxine botulique intradétrusorienne (Botox®) : quels sont les items indispensables ? Résultats d'un consensus Delphi d'experts du Groupe d'étude de neuro-urologie de langue française (GENULF).

INTRODUCTION: Preoperative information before bladder wall injection of botulinum toxin A (Botox®) holds several essential facts to understand and retain by the patients. The aim of this study was a review of essential preoperative information items according to GENULF medical experts. METHOD: It was a prospective review from December 2015 to April 2016. Three Delphi rounds had been done from the Survey Monkey® software. The initial questionnaire was composed of items from the patient information sheet edited by the GENULF. Each item had been rated by the medical expert on a numeric scale of importance for patient information. The last round asked to experts to confirm items eventually selected. RESULTS: A list of 27 items regarded as essentials for patient information had been checked by experts after three Delphi rounds, confirmed by 15/19 experts (75%). Best rated items were "learning self-catheterisation is essential" (mean interest 8,5/9 ; number of rate 8 or 9: 15), "kidney are protected over the long term" (mean interest 8,3/9 ; number of rate 8 or 9: 15), "efficiency is 6 to 9 months long" (mean interest 8,2/9 ; number of rate 8 or 9: 14). Discrepancies were mostly on lack of distinction between neurologic and non-neurologic patients. CONCLUSION: We identified accurate items considered as essential for preoperative information to patients before bladder wall injection of botulinum toxin A (Botox®) by a Delphi method recommended by HAS. LEVEL OF EVIDENCE: 4.

Investigation of intradetrusor onabotulinum toxin A efficacy and safety in older adults with urge urinary incontinence.

PURPOSE: Intradetrusor onabotulinum toxin A (BTX-A) has been demonstrated to be an effective treatment option for overactive bladder (OAB). However, concerns about frailty and frequent injections may deter its use in the elderly. This study aims to assess the safety, efficacy, and treatment duration of BTX-A in managing OAB in elderly women. METHODS: We retrospectively reviewed female patients aged 70 and above who were diagnosed with OAB with predominant urge urinary incontinence and underwent intravesical BTX-A treatment. We collected demographic and clinical data, with repeat BTX-A injections re-administered upon patient-reported symptom recurrence. RESULTS: Twenty-one female patients, median age 77 (range 71-92), were included. The median time between the first and second injection was 185 (84-448) days, 186 (105-959) days between the second and third injection, and increased to 206.5 (84-256) days between the third and fourth injection. However, the median interval trended downward after the fourth injection (Fig. 1). Patients with four or more injections had a shorter median interval between injections, 154 days, compared to those with fewer injections, 210 days. Two patients (6.9%) experienced urinary retention after the initial treatment, with 1 (2.2%) among a total of 46 subsequent treatments (Table 3). There were ten (13.3%) episodes of UTIs within 2 weeks of treatment. Patients reported improvement in symptoms following 93.3% of the injections. CONCLUSION: This real-world study demonstrates that BTX-A effectively controls OAB symptoms in elderly women, with just two injections annually. BTX-A appears safe and efficacious for treating OAB in elderly females.

Intradetrusor Versus Suburothelial Onabotulinum Toxin A in Adults with Neurogenic and Non-neurogenic Overactive Bladder Syndrome: A Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB). METHODS: This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I2 statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software. RESULTS: Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) (p = 0.24) and acute urinary retention (p = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies. CONCLUSIONS: Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.

Reducing the Impact of Headache and Allodynia Score in Chronic Migraine: An Exploratory Analysis from the Real-World Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study.

BACKGROUND: Chronic migraine (CM) is a disabling and hard-to-treat condition, associated with high disability and high cost. Among the preventive treatments, botulinum toxin A (BoNT-a) and monoclonal antibodies against the calcitonin gene-related protein (anti-CGRP mAbs) are the only disease-specific ones. The assessment of the disease burden is complex, and among others, tools such as the allodynia symptoms checklist (ASC-12) and headache impact test (HIT-6) are very useful. This exploratory study analysed the impact of these two therapies on migraine burden. METHODS: The RAMO study was a multicentre, observational, retrospective investigation conducted in two headache centres: the Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan) and the Fondazione Policlinico Campus Bio-Medico (Rome). This study involved patients with chronic migraine treated with mAbs or BoNT-A. We conducted a subgroup exploratory analysis on HIT-6 and ASC-12 scores in the two groups. The Wilcoxon rank-sum test, Fisher's exact test, and ANOVA were performed. RESULTS: Of 126 patients, 36 on mAbs and 90 on BoNT-A had at least one available follow-up. mAbs resulted in a mean reduction of -11.1 and -11.4 points, respectively, in the HIT-6 at 6 and 12 months, while BoNT-A was reduced -3.2 and -3.6 points, respectively; the mAbs arm resulted in mean reductions in ASC-12 at 6 and 12 months of follow-up of -5.2 and -6.0 points, respectively, while BoNT-A showed lesser mean changes of -0.5 and -0.9 points, respectively. The adjusted analysis confirmed our results. CONCLUSIONS: In this exploratory analysis, anti-CGRP mAbs showed superior effectiveness for HIT-6 and ASC12 compared to BoNT-A. Reductions in terms of month headache days (MHD), migraine disability assessment test (MIDAS), and migraine acute medications (MAM) were clinically relevant for both treatments.

A Retrospective Comparison of Onabotulinum Toxin A and Incobotulinum Toxin A in Terms of Efficacy, Tolerability, Duration of Effect, and Pain on Injection Administration Site for the Treatment of Chronic Migraine.

Background Onabotulinum toxin A (OnA) is a well-tolerated and effective treatment for chronic migraine (CM). However, based on research indications that incobotulinum toxin A (InA) would be equally effective, a Veterans Health Administration medical center mandated a two-year trial of InA as a more cost-effective alternative to OnA. Although InA is used for many similar indications as OnA, it is not Food and Drug Administration-approved for treating CM, and complications occurred in several patients with CM following this treatment change. We conducted this retrospective analysis to evaluate differences in the efficacy of OnA and InA and identify the reasons for the adverse effects of InA in some of these patients. Methods We performed a retrospective review of 42 patients who had been effectively treated with OnA and were then switched to InA. The differences between treatment responses to OnA and InA were assessed through the evaluation of pain on injection, number of headache days, and duration of action. Patients received injections at 10- to 13-week intervals. Those who reported severe pain on injection of InA were switched back to OnA. Results Severe burning pain on InA injection was reported by 38% of patients (nine males and seven females, i.e., a total of 16 patients out of 42 patients). One male patient reported the same degree of pain from both InA and OnA injections. A total of 66.7% of women with obesity and 83.3% of men with obesity or diabetes experienced severe pain on injection. Neither migraine suppression nor the duration of effect was significantly different between OnA and InA. Conclusions OnA is better tolerated than InA in the treatment of CM. InA appears to effectively suppress migraines, but some patients complain of a severe localized burning sensation during the injections. Some of these patients, all of whom were previously treated with OnA, requested to switch back to OnA. This suggested that InA is not equivalent to OnA in terms of tolerability and effectiveness. The present study found 2.38% of patients experienced an insufficient duration of effect with InA, and none with OnA. However, these lower rates may, in part, be due to variability in injection intervals in this sample, which could be because of scheduling considerations at the Harry S. Truman Veterans Health Administration Medical Center. In cases where OnA fails because of the development of antibodies, it might be reasonable to switch to InA treatment. Reformulation of InA with a pH-buffered solution may eliminate the difference in pain on injection. InA would then be a good alternative to OnA for treating CM.