Merz Pharmaceuticals GmbH Research Articles

The Hybrid Filler Technique: A 5-Year Retrospective Analysis.

The combination of calcium hydroxylapatite (CaHA) and hyaluronic acid fillers (CPM-HA, cohesive polydensified matrix-based hyaluronic acid fillers, Belotero® range, Merz Pharmaceuticals GmbH, Frankfurt, Germany), known as hybrid fillers, has emerged as a popular approach in aesthetic medicine. Premixed CaHA with CPM-HA offers several advantages, including enhanced tissue elevation and reduced early volume loss after injection. The objective of the present study is to assess the safety of premixing CaHA and CPM-HA fillers for rejuvenation purposes or as an aesthetic harmonization treatment. This retrospective study presents the clinical experience of two expert injectors who consistently used premixed CaHA and CPM-HA fillers for aesthetic treatments between March 2018 and December 2023. The premixed hybrid formulation was standardized and administered following a published protocol. A total of 2112 patients were treated, with meticulous follow-up over a minimum of one year. In the 2112 patients treated, only 5 minor adverse events (0.24%) were reported. The adverse events consisted of 4 non-inflammatory nodules of which 2 completely resolved with hyaluronidase, and 1 case of transient edema. Secondary findings consist of the treated areas, type of CPM-HA used and mixing ratios that were applied. The results from the current retrospective study, with the largest published cohort so far, are consistent with prior publications and strongly support a good safety profile of the CaHA:CPM-HA hybrid blend. 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 .

IncobotulinumtoxinA for Aesthetic Treatments: Review and Recommendations From Latin America.

As new aesthetic treatment techniques are developed, the understanding of botulinum toxin type A safety and treatment outcomes continues to evolve. This article was developed to provide a comprehensive up-to-date reference for clinicians using incobotulinumtoxinA (INCO; Xeomin/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) for aesthetic treatments. A Latin American panel of 11 physicians was assembled to discuss and develop recommendations on the use of INCO for aesthetic treatment based on the literature review and their private medical practice. The panel found that INCO is a highly purified botulinum toxin, without other clostridial proteins (hemagglutinins and nonhemagglutinins). IncobotulinumtoxinA has proven its efficacy and duration over time, maintaining response after multiple treatment cycles. This recommendation provides up-to-date information on the use of INCO for aesthetic treatment, focusing on the differential properties of this product regarding its purity, performance, customization, and patient satisfaction.

Botulinum neurotoxin type A in the interdisciplinary treatment of sialorrhea in adults and children-update and practice recommendations.

Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

Pain Reduction in Adult Patients with Limb Spasticity Following a Single IncobotulinumtoxinA Injection: an Analysis of Pooled Data from Phase 2 and 3 Studies (P14-11.008)

<h3>Objective:</h3> To assess pain relief in a large cohort of incobotulinumtoxinA-treated pts with spasticity-associated pain (SAP) using pooled data from mostly placebo-controlled phase 2/3 studies. <h3>Background:</h3> IncobotulinumtoxinA (incoA) has shown pain-relieving benefits in patients (pts) with limb spasticity in individual studies; data from large pt cohorts are lacking. <h3>Design/Methods:</h3> Pain severity was assessed with the Disability Assessment Scale (DAS; 0–3) in adults with upper limb SAP. A ≥1 point reduction in the DAS pain score from baseline [BL] to 4 weeks was defined as response. Between-treatment group response rates (overall and by BL pain severity – DAS mild, moderate, severe) and the proportion of pts with complete pain relief (DAS pain score=0) at 4 weeks after 1 injection of incoA (total dose ≤400U) or placebo were analyzed using <i>χ</i>² test. Overall between-group response rate differences were analyzed using logistic regression (presented as odds ratio [OR] and 95% confidence interval [CI]). <h3>Results:</h3> 542 (incoA: 413, placebo: 129) pts reported SAP at BL. At 4 weeks, a significantly higher proportion of incoA- vs placebo-treated pts achieved a response (52.1% vs 28.7%; p&lt;0.0001). IncoA-treated pts were more likely to achieve pain response vs placebo-treated pts (OR 2.7 [95% CI: 1.6–4.3]; p&lt;0.0001). Irrespective of BL pain severity, significantly higher response rates were observed with incoA vs placebo at 4 weeks (p&lt;0.02 all comparisons). Complete pain relief was achieved by significantly more incoA- vs placebo-treated pts at 4 weeks (26.9% vs 12.4%; p=0.0007). <h3>Conclusions:</h3> Pts receiving incoA vs placebo are significantly, by 2.7 times, more likely to achieve reduced upper limb SAP, irrespective of baseline pain severity, at 4 weeks post-injection thus supporting use of incoA in this setting. <b>Disclosure:</b> Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ipsen. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MERZ, ABBVIE, IPSEN. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MERZ, ABBVIE, IPSEN. Mr. Comes has received personal compensation for serving as an employee of Merz Pharmaceuticals GmbH. Michael Althaus has received personal compensation for serving as an employee of Merz Pharmaceuticals. Astrid Scheschonka has received personal compensation for serving as an employee of Merz Therapeutics. Dr. Simpson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Simpson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz.

Benefit of Multiple IncobotulinumtoxinA Injections for Pain Reduction in Adult Patients with Limb Spasticity: an Analysis of Pooled Data from Phase 2 and 3 Studies (P12-11.009)

<h3>Objective:</h3> To assess pain relief after multiple incobotulinumtoxinA (incoA) injections in a large sample of patients (pts) with limb spasticity-associated pain (SAP) using pooled data from six phase 2/3 studies (four placebo-controlled). <h3>Background:</h3> Repeated treatment with incoA has shown pain-relieving benefits in pts with limb spasticity in individual studies. <h3>Design/Methods:</h3> Adults with upper limb SAP received up to 4 incoA injections (total dose ≤400U) administered at 12- to 14-week intervals (injection cycles [ICs] 1–4; total observation period up to 56 weeks). Only IC 1 was placebo-controlled. Pain severity was assessed at control visits (CVs; 4 weeks after each injection) using the Disability Assessment Scale (DAS; pain scores ranging from 0 [no pain] to 3 [severe pain]). The proportions of pts with a response (defined as a reduction by ≥1 point in the DAS score from baseline to each CV) and with a complete response (DAS pain score=0) were assessed at every CV. Data were descriptively analyzed. As placebo-treated pts in IC 1 received incoA in subsequent cycles, they contributed data to the appropriate incoA CVs 1–4. <h3>Results:</h3> 515 pts with SAP at baseline were included in this analysis (515, 297, 263, and 181 pts at CVs 1–4, respectively). Response rates increased over time, being 53.0%, 63.3%, 66.9%, and 72.4% at CVs 1–4, respectively. Likewise, the proportion of pts with complete response increased over time, being 27.6%, 38.4%, 39.5%, and 43.6% at CVs 1–4, respectively. <h3>Conclusions:</h3> In pts with upper limb SAP, treatment response rates were sustained and showed a cumulative effect over 56 weeks after multiple incoA injections, with a complete pain relief in &gt;40.0% of pts. Results support the use of incoA in reducing upper limb SAP in affected adults. <b>Disclosure:</b> Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ipsen. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MERZ, ABBVIE, IPSEN. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MERZ, ABBVIE, IPSEN. Mr. Comes has received personal compensation for serving as an employee of Merz Pharmaceuticals GmbH. Michael Althaus has received personal compensation for serving as an employee of Merz Pharmaceuticals. Astrid Scheschonka has received personal compensation for serving as an employee of Merz Therapeutics. Dr. Simpson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Simpson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz.

Pooled Safety Analysis of IncobotulinumtoxinA in the Treatment of Neurological Disorders in Adults (P12-11.007)

<h3>Objective:</h3> To examine the pooled incidence of treatment-emergent adverse events (TEAEs) and immunogenicity by indication in sponsored incobotulinumtoxinA (INCO) clinical trials in adults. <h3>Background:</h3> The safety and efficacy of INCO in adult neurological disorders has been investigated in multiple prospective clinical trials, including several not yet published. A comprehensive assessment combining available data would provide additional insights into INCO safety. <h3>Design/Methods:</h3> TEAEs were identified in the integrated clinical database of Merz-sponsored placebo (PBO)-controlled studies in adults with cervical dystonia (CD), blepharospasm, upper limb (UL) and lower limb (LL) spasticity, sialorrhea and essential tremor of the UL. Overall incidences of TEAEs and the categories of serious TEAEs (SAEs), TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (AESIs; indicating possible toxin spread) and treatment-related (TR) events were determined for INCO and PBO after a single injection cycle and for INCO after multiple cycles; the most frequent TEAEs, TR-TEAEs and TR-AESIs after a single cycle of INCO were summarized. Neutralizing antibody (NAb) testing was performed in most studies. <h3>Results:</h3> After a single cycle, the incidences of overall TEAEs were similar between INCO and PBO in all indications, although between-indication differences were observed. Most TEAEs were mild to moderate in intensity, and only one subject experienced a TR-SAE. Few TEAEs led to discontinuation of INCO; there were no fatal TEAEs in subjects receiving INCO. In general, repeated cycles did not increase the incidences of any TEAE category. TR-TEAEs affecting ≥1% of patients were uncommon in patients with spasticity. TR-AESIs across all indications were most commonly muscular weakness and dry mouth. Few subjects developed NAb; the vast majority of those positive at the end of the study were also positive at baseline. <h3>Conclusions:</h3> Results of this pooled analysis support and extend the favorable safety and tolerability profile of INCO for the treatment of adult neurological disorders. <b>Disclosure:</b> Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda Therapeutics. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck LTD. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan Inc. Dr. Comella has received personal compensation in the range of $0-$499 for serving as a Consultant for Merz. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Comella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Dr. Comella has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Aeon. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz . Dr. Comella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ipsen. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceutical. Dr. Comella has received publishing royalties from a publication relating to health care. Dr. Comella has received publishing royalties from a publication relating to health care. Michael Hast has received personal compensation for serving as an employee of Merz. Angelika Hanschmann has received personal compensation for serving as an employee of Merz Pharmaceuticals GmbH.

A split-face comparative performance evaluation of injectable hyaluronic acid-based preparations HCC and CPM-HA20G in healthy females.

Skin revitalizers are used for skin quality improvement purposes. Hyaluronan hybrid cooperative complexes (HCC, Profhilo®, IBSA Pharmaceuticals) are an anti-aging treatment with a large amount of pure hyaluronic acid (HA) based on stable, cooperative, and hybrid complexes. Cohesive polydensified matrix Hyaluronic Acid (CPM-HA20, Belotero Revive®, Merz Pharmaceuticals GmbH) is a slightly cross-linked HA (20 mg/ml) with glycerol (17.5mg/ml). To evaluate the performance of HCC and CPM-HA20G for skin quality improvement in healthy female subjects. This was a split-face, single-blinded study that enrolled 24 healthy female subjects. Injections were given on three separate occasions. HCC was injected on the right cheek, while CPM-HA20G was injected on the left cheek. A battery of skin property measurements was used to evaluate the skin. Skin properties and overall satisfaction were analyzed using mixed models with the values at baseline, at week 1, week 8, and week 14 as an outcome and a random effect of subject and fixed effects of treatment, visit, and the treatment by visit interaction. Both products showed evidence of effect relative to baseline on surface hydration (AU), elasticity (N/m) TEWL (g/m2 h), and melanin (AU). CPM-HA20G also showed significant evidence of effect relative to baseline on water content (%), and HCC on pore count (n) and hemoglobin (AU). Satisfaction reported by the subjects themselves showed positive trends of satisfaction over time for multiple skin properties. There were no significant differences between the tested products in the observed skin characteristics over time. These devices are effective and safe treatments for skin quality improvement, especially moisturization, with high patient satisfaction and generally mild and transient side effects.

Treatment of Sialorrhea with Botulinum Neurotoxin Type A - Consensus Practice Recommendations for Children and Adults

ZusammenfassungSialorrhoe, ein unkontrollierter, übermäßiger Speichelfluss aus dem Mund und in den Schlund, tritt als Begleitsymptom bei verschiedenen, v. a. neurologischen Erkrankungen im Kindes- und Erwachsenenalter auf. Mit IncobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH) steht seit 2019 ein zugelassenes Medikament für die Behandlung der Sialorrhoe zur Verfügung. Indikationsstellung, mögliche Therapieziele, Praxis der Behandlung und Management in besonderen Behandlungssituationen bilden den Schwerpunkt dieser konsentierten Praxis-Empfehlungen, die in interdisziplinärer Zusammenarbeit erfahrener Anwender entwickelt wurden. Ziel ist, den Zugang zur Therapie zu erleichtern und einen Beitrag zu einer qualifizierten Botulinumtoxin-Therapie zu leisten.

Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects.

ObjectiveTo confirm the efficacy and safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH; total dose 400 U) in Japanese subjects with lower limb (LL) poststroke spasticity using the Modified Ashworth Scale spasticity score for the plantar flexors (MAS-PF).MethodsThis phase III study (Japic clinical study database No. CTI-153030, 7 October 2015) included a double-blind, 12-week main period (MP) in which 208 subjects were randomized to receive one injection cycle of incobotulinumtoxinA 400 U (n = 104) or placebo (n = 104) in the pes equinus muscles, and an open-label extension (OLEX) that enrolled 202 subjects who received three injection cycles, 10–14 weeks in duration (the last cycle was fixed at 12 weeks). Changes in MAS-PF for incobotulinumtoxinA vs. placebo from baseline to Week 4 of the MP and to the end-of-cycle visits in the OLEX were evaluated.ResultsThe area under the curve for the change in MAS-PF was statistically significantly greater with incobotulinumtoxinA vs. placebo in the MP (mean: −7.74 vs. −4.76; least squares mean: −8.40 vs. −5.81 [p = 0.0041]). In the OLEX, mean changes in MAS-PF from baseline to end-of-study showed continued improvement with repeated injections. No new safety concerns were observed with the incobotulinumtoxinA treatment. Its efficacy and safety were consistent regardless of the length of the injection cycle interval in the OLEX.ConclusionThis study demonstrated that incobotulinumtoxinA (total dose 400 U) is an effective and a well-tolerated treatment for LL spasticity in Japanese subjects using flexible injection intervals of 10–14 weeks.

Duration and onset of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naïve subjects

Objective Blepharospasm is a focal dystonia whereby excessive eyelid muscle contractions cause involuntary eye closure. Botulinum neurotoxin type A (BoNT-A) injections are an approved treatment. This randomized placebo-controlled trial (NCT01896895; EudraCT number 2012-004821-26) assessed the efficacy, safety, and treatment effect duration of incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals GmbH), a BoNT-A formulation without complexing proteins, in BoNT-A-naïve adults with blepharospasm. Methods Subjects received incobotulinumtoxinA 50 U, 25 U (total dose) or placebo during a main study period (MP; 6–20 weeks). Patients needing a second injection received incobotulinumtoxinA ≤70 U in an open-label extension period (EP; 6–20 weeks). Treatment effect durations were time from first injection to EP injection or final MP visit and from EP injection to end-of-study visit. Times to effect onset and to waning of effect (MP) were time from injection to first subject-assessed onset effect and time from injection to subject-reported waning of effect, respectively. Results Of 61 subjects, 39 entered the EP. During the MP, median duration of treatment effect was longer with incobotulinumtoxinA 50 U (20 weeks) versus incobotulinumtoxinA 25 U (11 weeks) or placebo (6 weeks). Median duration of treatment effect was 20 weeks during the EP. Median time to effect onset was 5, 7, and 14 days with 50 U, 25 U, and placebo, respectively (p = .022 for 50 U versus placebo). Median time to waning of treatment effect was comparable between groups. Conclusion Subjects reported an effect onset from 5 days after injection lasting up to 20 weeks (maximum observation period). Data indicate that incobotulinumtoxinA re-treatment of blepharospasm may not be required at fixed 12-week intervals and provide evidence for a patient-tailored approach.

The efficacy of onion extract in the management of subsequent abdominal hypertrophic scar formation.

Development of postoperative scars is often a problem. This study aimed to evaluate the efficacy of gel containing Allium cepa extract, allantoin and heparin (Contractubex, Merz Pharmaceuticals GmbH, Frankfurt, Germany) in reducing scarring after a caesarean section by comparing it with a control group, and also intra-individually, using the Vancouver Scar Scale (VSS). A total of 120 patients who underwent a second elective caesarean delivery and who presented with hypertrophic scar development after their first caesarean section were included in the study. A scar revision was performed for all patients during the second caesarean operation. Patients in the study group (n=60) were advised to apply the topical scar gel postoperatively for a period of 6 months. The control group (n=60) received no treatment. Significant reductions were observed in the vascularity, pigmentation and height subgroups of the VSS for those in the group who continued the treatment to 24 weeks. An intra-individual analysis showed that the gel effectively reduced scarring after the second caesarean section. The prophylactic use of the gel to reduce scar development offers better results for vascularity, pigmentation and height subscales of the VSS after surgical removal of the primary caesarean scar during the second caesarean section. The results were better both intra-individually, and also in comparison with the control group and support the use of a gel containing Allium cepa extract, allantoin and heparin to reduce scarring after a caesarean section.

Efficacy and safety of IncobotulinumtoxinA in the treatment of lower limb spasticity in Japanese subjects

Objective: To confirm the efficacy and safety of botulinum toxin type A (BoNT-A) treatment incobotulinumtoxinA (INCO; Xeomin®, Merz Pharmaceuticals GmbH) in Japanese subjects from study sites in Japan with post-stroke spasticity in the lower limb (LL), using the Modified Ashworth Scale (MAS) spasticity score for the plantar flexors.

IncobotulinumtoxinA for the Treatment of Blepharospasm in Toxin-Naïve Subjects: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial.

This study aimed to assess the efficacy/safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH) in botulinum neurotoxin-naïve subjects with blepharospasm. Botulinum neurotoxin-naïve subjects (≥ 12months without botulinum neurotoxin treatment for blepharospasm) received single-dose incobotulinumtoxinA 50 U, 25U, or placebo. Subjects were followed for 6-20weeks (main period). Qualified subjects entered an open-label extension period and received another incobotulinumtoxinA injection (≤ 70 U). The primary efficacy variable was change from baseline in the Jankovic Rating Scale (JRS) severity subscore at the main period of week 6. Other efficacy variables included changes in the Blepharospasm Disability Index score and JRS frequency subscore and sumscore. Adverse events were monitored. Sixty-one subjects were randomized (main period: incobotulinumtoxinA 50 U, n = 19; incobotulinumtoxinA 25 U, n = 22; placebo, n = 20); 39 entered the open-label extension period (9, 14, and 16 subjects from the incobotulinumtoxinA 50 U, incobotulinumtoxinA 25 U, and placebo groups [main period], respectively, changed to open-label extension period dosing). A statistically significantly greater reduction in JRS severity subscore was reported for subjects receiving incobotulinumtoxinA 50 U versus placebo (ANCOVA, least square mean difference: -1.2, p = 0.0004). Subjects receiving incobotulinumtoxinA experienced improvements in other efficacy variables versus baseline and/or placebo. Sustained clinical improvements and low adverse event rates (22.2-42.1%) were observed. This is the second placebo-controlled, double-blind study that demonstrates favorable efficacy/safety of incobotulinumtoxinA in subjects with blepharospasm. IncobotulinumtoxinA is the first botulinum neurotoxin that could fulfill the American Academy of Neurology criteria for a Level A recommendation for blepharospasm.Trial registration ClinicalTrials.gov identifier, NCT01896895.

Facial skin revitalization with CPM®-HA20G: an effective and safe early intervention treatment.

BackgroundHyaluronic acid (HA) fillers are popular for the treatment of signs of facial skin aging.ObjectiveThe objective of this study was to confirm the performance and safety of a new cohesive polydensified matrix HA filler ([CPM®-HA20G, Belotero Revive®, lidocaine-free], Merz Pharmaceuticals GmbH, Frankfurt, Germany) for the treatment of early signs of facial skin aging by use of biophysical measurements as well as subject and investigator satisfaction.MethodsTwenty-five healthy female subjects with signs of facial skin aging were enrolled in this open-label, rater-blinded, observational post-market clinical follow-up study, and received 20 micropuncture treatments of 50 µL CPM®-HA20G each into the lower cheek area at three injection visits 4 weeks apart. Objective biophysical assessments were conducted to demonstrate effects on viscoelastic properties of the skin, surface roughness, tone and radiance, and hydration, at baseline and at all follow-up visits up to 36 weeks.ResultsCPM®-HA20G significantly increased gross elasticity of the skin (at weeks 9 and 12), skin firmness (up to week 24), skin tone and radiance and skin hydration (all up to 36 weeks). Significant reduction of skin fatigue (up to 9 weeks), skin roughness (up to 28 weeks), and redness (up to 36 weeks) was also observed. Subjects and blinded investigator were highly satisfied with the treatment outcomes. The treating investigator reported a high level of satisfaction with the ease of injection and the clinical performance of the device. Moreover, data demonstrated a good safety profile of the device.ConclusionCPM®-HA20G is considered to be an effective and safe HA injectable for skin revitalization in patients suffering from signs of skin aging and loss of skin elasticity. It seems to be a perfect early intervention approach in patients that do not need volumizing treatment and a combination approach in older patients with more pronounced aging.

Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study.

Objective:To evaluate safety (primary objective) and efficacy of increasing doses (400 U up to 800 U) of incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals GmbH) for patients with limb spasticity.Methods:In this prospective, single-arm, dose-titration study (NCT01603459), patients (18–80 years) with spasticity due to cerebral causes, who were clinically deemed to require total doses of 800 U incobotulinumtoxinA, received 3 consecutive injection cycles (ICs) with 400 U, 600 U, and 600–800 U incobotulinumtoxinA, respectively, each followed by 12–16 weeks' observation. Outcomes included adverse events (AEs), antibody testing, Resistance to Passive Movement Scale (REPAS; based on the Ashworth Scale), and Goal Attainment Scale.Results:In total, 155 patients were enrolled. IncobotulinumtoxinA dose escalation did not lead to an increased incidence of treatment-related AEs (IC1: 4.5%; IC2: 5.3%; IC3: 2.9%). No treatment-related serious AEs occurred. The most frequent AEs overall were falls (7.7%), nasopharyngitis, arthralgia, and diarrhea (6.5% each). Five patients (3.2%) discontinued due to AEs. No patient developed secondary nonresponse due to neutralizing antibodies. Mean (SD) REPAS score improvements from each injection to 4 weeks postinjection increased throughout the study (IC1: −4.6 [3.9]; IC2: −5.9 [4.2]; IC3: −7.1 [4.8]; p < 0.0001 for all). The proportion of patients achieving ≥3 (of 4) treatment goals also increased (IC1: 25.2%; IC2: 50.7%; IC3: 68.6%).Conclusion:Escalating incobotulinumtoxinA doses (400 U up to 800 U) did not compromise safety or tolerability, enabled treatment in a greater number of muscles/spasticity patterns, and was associated with increased treatment efficacy, improved muscle tone, and goal attainment.ClinicalTrials.gov identifier:NCT01603459.Classification of evidence:This study provides Class IV evidence that, for patients with limb spasticity, escalating incobotulinumtoxinA doses (400 U up to 800 U) increases treatment efficacy without compromising safety or tolerability.

Therapeutic Efficacy of Combination Therapy Using Oral Cyclosporine with a Dietary Supplement (Pantogar®) in Twenty-Nail Dystrophy.

BackgroundTwenty-nail dystrophy (TND) is an acquired idiopathic disease characterized by dull, thin, lusterless, and fragile nails with fissuring, small regular pits, and excessive longitudinal ridging. Although various treatment modalities have been performed in order to treat TND, the effects of these treatments are controversial.ObjectiveTo evaluate the effectiveness of oral cyclosporine in TND.MethodsA total of 38 patients with TND were treated with combination therapy using oral cyclosporine with a pantothenic acid complex-based dietary supplement (Pantogar®; Merz Pharmaceuticals GmbH, Germany), whereas 44 patients were treated with the pantothenic acid complex-based dietary supplement alone. The therapeutic efficacy in each group was retrospectively evaluated using medical records and clinical photographs.ResultsThe cyclosporine therapy group had significantly more patients whose improvement was rated as almost clear, marked, or moderate compared to the control group (p<0.001). While the mean CHATS (Color, Hyperkeratosis, Area, Thickness, Separation) score of the cyclosporine therapy group was decreased by 13.45 (from 30.95 to 17.5) after treatment, the mean CHATS score of the control group was only decreased by 8 (from 29.43 to 21.43, p<0.001). Moreover, greater Dermatology Life Quality Index changes after treatment were observed in the cyclosporine therapy group (p=0.085).ConclusionOral cyclosporine can be a valuable therapeutic option in patients with TND.

The Rainbow Scale: A Simple, Validated Online Method to Score the Outcome of Aesthetic Treatments

Photographs have become an important integral part of documentation in an aesthetic surgery practice, both for medico-legal as well as scientific purposes.1 Only by evaluating pre- and postoperative photographic documentation are we able to evaluate our success and treatment outcomes in an objective way. Several photographic scales have already been developed for this purpose.2-4 However, an easy online system to evaluate aesthetic outcomes in a validated, fast, reliable, and standardized way is still lacking. We have therefore designed what we call the “Rainbow Scale” method based on the Merz Scales (Merz Pharmaceuticals GmbH, Frankfurt, Germany) (Figure 1).2 In this online system, 6 photographs are presented in a block of two rows of 3 photographs. The photograph of the patient to be evaluated is located in the central position of the lower row. Other photographs show the five grades of severity of the area to be evaluated, with the lowest score left of the photograph to be evaluated, the second score on the upper left side, etc. until the highest score on the lower right side of the photograph. The different scores are thus presented around the patient in a rainbow fashion. …

Calcium hydroxylapatite for jawline rejuvenation: consensus recommendations

Age-associated volume loss is now known to play an important role in the structural changes of the aging face. In the lower face, this manifests as drooping of the corners of the mouth and jowl leading to a loss of the oval jawline of youth. Jawline reshaping by replacing volume has therefore become an indispensable component of modern facial rejuvenation. Calcium hydroxylapatite (CaHA; Radiesse® , Merz Pharmaceuticals GmbH, Frankfurt, Germany) is an injectable filler with a cosmetic indication for tissue augmentation. The ability of calcium hydroxylapatite to provide immediate and long-lasting volume enhancement makes it an ideal agent for restoring an oval jawline. This consensus statement has been developed to assist clinicians who would like to gain more experience in the use of volumizing agents to achieve an optimal outcome with this procedure. Using the recently developed Merz Aesthetics Scale® for jawline, the consensus provides a treatment protocol for individuals at each stage of oval loss and presents a series of before and after images to illustrate the improvements that can be achieved. Specific recommendations for calcium hydroxylapatite including type of anesthesia, injection techniques, volume for injection, use in combination with other procedures, and expected duration of corrections are provided. Techniques for minimizing and managing expected problems and potential complications are also described. Calcium hydroxylapatite is appropriate for treating patients at any stage of oval loss.

Multicenter, Randomized, Phase III Study of a Single Dose of IncobotulinumtoxinA, Free from Complexing Proteins, in the Treatment of Glabellar Frown Lines

Botulinum toxin type A is a proven, effective aesthetic treatment for glabellar frown lines. IncobotulinumtoxinA (NT 201, Xeomin/Xeomeen/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a 150-kDa botulinum toxin type A free of complexing proteins. To assess the efficacy and safety of incobotulinumtoxinA in a randomized, double-blind, placebo-controlled, Phase III study in patients with moderate to severe glabellar frown lines. Two hundred seventy-six patients were randomized 2:1 to receive a single injection of 20U of incobotulinumtoxinA or placebo, respectively. Efficacy was assessed at day 30 using a Food and Drug Administration-mandated composite endpoint; a responder was defined as a patient with a 2-point or greater improvement in glabellar frown lines on a 4-point scale as assessed by investigator and patient. Safety was assessed periodically through Day 120. Treatment with a single dose of incobotulinumtoxinA was significantly superior to placebo in the treatment of glabellar frown lines at Day 30 using the composite endpoint (p<.001), with investigators and patients assessing glabellar frown lines as significantly more improved after incobotulinumtoxinA injection than with placebo (p<.001). IncobotulinumtoxinA was well tolerated. A single dose of 20U of incobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar frown lines using new Food and Drug Administration efficacy variables.

Clinical Relevance of Botulinum Toxin Immunogenicity

Botulinum toxin type A is a 150 kD protein produced by Clostridium botulinum, which exists in a complex with up to six additional proteins. The ability of botulinum toxin to inhibit acetylcholine release at the neuromuscular junction has been exploited for use in medical conditions characterized by muscle hyperactivity. As such, botulinum toxin is widely recommended by international treatment guidelines for movement disorders and it has a plethora of other clinical and cosmetic indications. The chronic nature of these conditions requires repeated injections of botulinum toxin, usually every few months. Multiple injections can lead to secondary treatment failure in some patients that may be associated with the production of neutralizing antibodies directed specifically against the neurotoxin. However, the presence of such antibodies does not always render patients non-responsive. The reported prevalence of immunoresistance varies greatly, depending on factors such as study design and treated indication. This review presents what is currently known about the immunogenicity of botulinum toxin and how this impacts upon patient non-response to treatment. The complexing proteins may act as adjuvants and stimulate the immune response. Their role and that of neutralizing and non-neutralizing antibodies in the response to botulinum toxin is discussed, together with an assessment of current neutralizing antibody measurement techniques. Botulinum toxin preparations with different compositions and excipients have been developed. The major commercially available preparations of botulinum toxin are Botox® (onabotulinumtoxinA; Allergan, Inc., Ireland), Dysport® (abobotulinumtoxinA; Ipsen Ltd, UK), and Xeomin® (incobotulinumtoxinA; botulinum toxin type A [150 kD], free from complexing proteins; NT 201; Merz Pharmaceuticals GmbH, Germany). The new preparations of botulinum toxin aim to minimize the risk of immunoresistance in patients being treated for chronic clinical conditions.