Deoxycholic Acid Injection Research Articles

Commentary on ATX-101 (Deoxycholic Acid Injection) for Paradoxical Adipose Hyperplasia Secondary to Cryolipolysis.

Commentary on ATX-101 (Deoxycholic Acid Injection) for Paradoxical Adipose Hyperplasia Secondary to Cryolipolysis.

Abstract 67: Real-World Experience with 100 Consecutive Patients Undergoing Injection Adipocytolysis for Neck Contouring with ATX-101 (Deoxycholic Acid): An Updated Report with 2-Year Analysis

PURPOSE: In 2015, deoxycholic acid (DCA) injection was approved for treatment of mild-to-moderate convexity associated with submental fat. The efficacy and safety of submental DCA injection have been demonstrated in four phase 3 randomized controlled trials (RCTs), however, critical assessment of DCA injection in conventional clinical practice is lacking. In a previous report, we presented initial findings from our experience with 100 consecutive patients administered submental DCA. This study describes and evaluates real-world experience with submental DCA injection in a clinical practice setting, and provides an update to our previous report, accounting for additional treatment sessions during long-term follow-up. METHODS: This prospective, single-arm, observational study was conducted at a single clinic (private practice) between June 2015 and June 2017. Experience through February 2016 was previously published. The study involved 100 consecutive patients, aged between 18 and 80 years, seeking improvement in convexity/fullness associated with submental fat. Treatment involved DCA injection to the preplatysmal submental fat using an area-adjusted DCA dose of 2 mg/cm2, with up to 75 injections (0.2 mL per injection [maximum, 15 mL]) per treatment session for a maximum of 6 sessions. Treatment response was assessed using the clinician-reported submental fat rating scale CR-SMFRS (0 = absent; 1 = mild; 2 = moderate; 3 = severe; and 4 = extreme) and confirmed by independent physician review of photographs at 1 and 5 to 7 weeks posttreatment. Treatment response was defined as an improvement of ≥1 point. AEs, including injection-site AEs such as local edema, numbness, and tenderness were monitored at each follow-up visit. Patient demographics, response, and safety were compared between patients who underwent single versus multiple treatment sessions. RESULTS: Since the prior published report, 17 patients have undergone additional treatment sessions. Overall, one hundred patients have had 195 treatment sessions: 41, 36, 14, 6, 2, and 1 patient had 1, 2, 3, 4, 5, and 6 sessions, respectively. In the multiple-treatment-session (MTS) group, most (36/59 [61.0%]) patients had 2 sessions; 14 (23.7%) had 3 sessions, 6 (10.2%) had 4 sessions, 2 (3.4%) had 5 sessions, and 1 (1.7%) had 6 sessions. A mean (SD) of 6.7 (2.3) mL of DCA was administered per treatment session, with significantly more DCA administered to the MTS than single-treatment-session (STS) group (6.8 [2.3] vs 6.1 [2.2] mL/session; p = .049). Overall, 33 of 36 (91.7%) patients in the STS group and all 59 (100.0%) patients in the MTS group had an improved CR-SMFRS score by ≥1 point. Local edema, numbness, and tenderness were reported for a mean (SD) of 7.1 (5.1), 27.9 (11.3), and 3.5 (3.5) days post-treatment, respectively. CONCLUSIONS: Longer-term follow-up of submental DCA injections demonstrated that patients will likely require ≥2 sessions to achieve the desired aesthetic goal in a private practice setting. Both single- and multiple-treatment sessions were generally well tolerated. S.M. Shridharani:; Allergan.; Galderma.; Merz.; Sientra. G.M. Tisch: None.

Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data From the Phase 3 REFINE Trials.

BackgroundATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin.ObjectivesTo evaluate the efficacy and safety of ATX-101 by treatment session.MethodsThis post hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile.ResultsIn both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101–treated patients achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or patient assessment. Furthermore, 19.1% of ATX-101–treated patients (vs 3.9% of placebo-treated patients) received fewer than 6 treatment sessions owing to patient satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions.ConclusionsAlthough up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101–treated patients achieved an improvement in SMF within 2 to 4 treatment sessions.Level of Evidence: 3

Deoxycholic Acid Injection as an Effective Treatment for Reduction of Posterior Upper Torso Brassiere Strap Adiposity.

Deoxycholic Acid Injection as an Effective Treatment for Reduction of Posterior Upper Torso Brassiere Strap Adiposity.

Manual acupuncture relieves bile acid-induced itch in mice: the role of microglia and TNF-α.

Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.

ATX-101 (Deoxycholic Acid Injection) Treatment in Men: Insights From Our Clinical Experience.

Excess submental fat (SMF), also called a double chin, is an area of concern for men that can be addressed clinically. ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada, Australia, and various European countries) is the first injectable approved for reduction of SMF. To share the authors' clinical experience using ATX-101 in men with submental fullness and offer insights regarding how this treatment may be presented to men as an option to improve their submental profile. Retrospective review of the authors' medical records for male patients treated with ATX-101. To allow for fewer ATX-101 treatments, it is recommended that a large surface area be treated at the first session. The positive changes and outcomes achieved with ATX-101 build confidence between the physician and patient, which often leads to male patients seeking other aesthetic treatments to improve their overall appearance. ATX-101 treatment is often an effective introduction to aesthetic medicine for men.

Commentary on ATX-101 (Deoxycholic Acid Injection) Treatment in Men.

Commentary on ATX-101 (Deoxycholic Acid Injection) Treatment in Men.

Abstract: Alopecia in Male Patients Treated with ATX-101 (Deoxycholic Acid) for Submental Fullness

INTRODUCTION: Deoxycholic acid is approved for minimally invasive treatment of submental fat. Safety profiles from pivotal studies did not report on the potential adverse effect of localized alopecia.1,2 Knowledge about any potential adverse event, including alopecia, is important for informed consent and setting patient expectations. This study is the first to characterize alopecia in patients undergoing deoxycholic acid treatment for submental fat. METHODS: A retrospective review was conducted of 171 patients (66 male) treated with deoxycholic acid in the submental region at a single-center between January 2015-December 2016. Deoxycholic acid was injected into the preplatysmal submental fat (0.2 mL per injection of 10mg/mL to achieve a dose of 2mg/cm2) for a maximum of 6 treatments. Patient characteristics, treatment plan, and severity/resolution of alopecia was analyzed. RESULTS: Alopecia was reported in 15% of male patients (none observed in female patients). Severity of alopecia in follow-up patients (n=8) ranged from diffuse/mild to 6 patches of alopecia, and was not associated with dose delivered or number of injections. Alopecia was noticed a median 31.5 days after injection (range 15–94 days). Five of eight patients reported improvement or complete resolution of alopecia. Six of eight patients experienced alopecia after the first treatment. Five of eight patients seeked further treatment despite alopecia. CONCLUSION: Alopecia is a real adverse event following treatment of deoxycholic acid for submental fat reduction in males that occurs approximately 1 month after treatment. Severity is not dependent on treatment plan, and is likely due to patient characteristics. While a majority of patients had improvement or resolution, longer follow-up is needed to further assess the transiency of injection-induced alopecia. Importantly, a majority of patients continued to seek further treatment, suggesting patient-impact of this alopecia was low compared to the benefits of submental fat reduction. Reference Citations: 1. Kythera Biopharmaceuticals I. Dermatologic and ophthalmic drugs advisory committee briefing document: ATX-101 (deoxycholic acid) injection. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DermatologicandOphthalmicDrugsAdvisoryCommittee/UCM436604.pdf. Accessed February 26, 2017. 2. Dayan SH, Humphrey S, Jones DH, et al. Overview of ATX-101 (Deoxycholic Acid Injection): A Nonsurgical Approach for Reduction of Submental Fat. Dermatol Surg. 2016;42:S263-S270.

Abstract: Novel Expanded Safe Zone System for Treatment of Submental Fullness with ATX-101 (Deoxycholic Acid)

INTRODUCTION: Deoxycholic acid is approved for minimally invasive treatment of submental fat. Most standard markings treat only a small central area of submental fullness to avoid complications, especially marginal mandibular nerve paresis.1,2 This one-size-fits-all approach likely undertreats fuller necks. Knowledge of the submental fat pads provides an anatomical basis for patient-customized treatment with deoxycholic acid.3,4 This study shows the first real-world use of a novel Expanded Safe Zone (ESZ) system and to characterize its safety profile. METHODS: A retrospective review was conducted of 121 patients treated at a single-center between June 2015-December 2016. Each patient was assessed for change in neck anatomy in each of the six regions of the ESZ system, thereby identifying the preplatysmal fat target treatment regions. Deoxycholic acid was injected into each respective region (0.2 mL per injection of 10mg/mL to achieve a dose of 2mg/cm2) for a maximum of 6 treatments. Response was defined as decreased palpable and/or visible fullness due to decreased overall adipose deposits. Injection-site adverse events (AEs) and other AEs were recorded at each visit. RESULTS: Improvement in submental fullness was achieved in 97.5% of patients with follow-up (n=79). AEs included bruising (11.9%), localized tenderness (100%, mean 3.9 days), edema (99.3%, mean 7.7 days), numbness (99.1%, mean 27.6 days), nausea (0.01%), vomiting (0%), headache (2.5%), localized alopecia (5.8%), and paresis (5.8%, mean 27.1 ± 10.1 days, median 30 days, maximum 37 days). CONCLUSION: Postinjection tenderness, edema, and numbness had a higher incidence in this study than pivotal studies (69.5%, 60.4%, 13.8%, respectively),5 likely due to increased area treated and increased dose per treatment, but were transient and resolved in a similar time period (<30 days). Paresis had a similar incidence rate compared to pivotal studies (5.8% vs. 4.3%), but had a shorter median duration (30 days vs. 42 days). This study shows real-world feasibility and initial safety and efficacy using the ESZ for submental fat reduction. This individualized treatment plan is likely to result in better outcomes than a one-size-fits-all approach without increasing adverse events. Reference Citations: 1. Dayan SH, Jones DH, Carruthers J, et al. A Pooled Analysis of the Safety and Efficacy Results of the Multicenter, Double-Blind, Randomized, Placebo-Controlled Phase 3 REFINE-1 and REFINE-2 Trials of ATX-101, a Submental Contouring Injectable Drug for the Reduction of Submental Fat. Plast Reconstr Surg. 2014;134:123. 2. Brackeen A. A template for estimating doses of deoxycholic acid for submental fat fullness. J Am Acad Dermatol. 2016;75(4):e151-e152. 3. Hatef DA, Koshy JC, Sandoval SE, Echo AP, Izaddoost SA, Hollier LH. The submental fat compartment of the neck. Semin Plast Surg. 2009;23(4):288–291. 4. Pilsl U, Anderhuber F. The chin and adjacent fat compartments. Dermatol Surg. 2010;36(2):214–218. 5. Kythera Biopharmaceuticals I. Dermatologic and ophthalmic drugs advisory committee briefing document: ATX-101 (deoxycholic acid) injection. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DermatologicandOphthalmicDrugsAdvisoryCommittee/UCM436604.pdf. Accessed February 26, 2017.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: ERRATUM.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: ERRATUM.

Social perceptions before and after treatment with ATX-101 (deoxycholic acid injection) for reduction of submental fat

Social perceptions before and after treatment with ATX-101 (deoxycholic acid injection) for reduction of submental fat

Early Experience in 100 Consecutive Patients With Injection Adipocytolysis for Neck Contouring With ATX-101 (Deoxycholic Acid).

Deoxycholic acid (DCA) is approved for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat. To assess early treatment experience with DCA injection in a clinical practice setting. In this single-center, prospective, single-arm, observational study, 100 consecutive patients seeking to decrease submental fullness received subcutaneous DCA (2 mg/cm) injections in the submental area (maximum of 6 sessions at ≥1 month intervals). Treatment response was assessed 1 and 5 to 7 weeks posttreatment using the clinician-reported submental fat rating scale (CR-SMFRS) and retrospective independent photograph review by 2 physicians. Overall, 100 patients had 152 treatment sessions (58, 33, 8, and 1 patients had 1, 2, 3, and 4 sessions, respectively). CR-SMFRS score improved by ≥1 point from baseline in 88 (88%) patients; of these, 46, 33, 8, and 1 patients had 1, 2, 3, and 4 sessions, respectively. Local edema, numbness, and tenderness were reported for a mean (SD) of 7.7 (5.3), 28.5 (11.4), and 3.5 (3.5) days, respectively. Two patients experienced marginal mandibular nerve paresis. Deoxycholic acid injection, a minimally invasive procedure for neck contouring, was effective and generally well tolerated in the private practice setting.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat

Prevention and Management of Injection-Related Adverse Effects in Facial Aesthetics: Considerations for ATX-101 (Deoxycholic Acid Injection) Treatment

ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc. [an affiliate of Allergan plc, Dublin, Ireland]) was approved in 2015 in the United States (Kybella) and Canada (Belkyra) for submental fat reduction. As expected, injection-site reactions such as pain, swelling, and bruising, which were mostly mild or moderate and transient, were common adverse events (AEs) reported in clinical trials. An exploratory Phase 3b study investigating interventions for management of injection-site AEs associated with ATX-101 treatment was recently completed. Based on its results, literature review, and our clinical experiences, we have put forward considerations for management of AEs associated with ATX-101 treatment in clinical practice. Pretreatment with oral ibuprofen and/or acetaminophen an hour before treatment and preinjection with epinephrine-containing buffered lidocaine 15 minutes before treatment can help with management of pain and bruising. Cold application to the treated area before and immediately after the procedure may help to reduce pain (if local anesthetic preinjection is not performed) and swelling. Discontinuing medications/supplements that result in increased anticoagulant or antiplatelet activity 7 to 10 days before ATX-101 treatment, when possible, can reduce the risk of bruising. In summary, injection-site AEs associated with ATX-101 treatment can be effectively managed with commonly used interventions.

Proper Technique for Administration of ATX-101 (Deoxycholic Acid Injection): Insights From an Injection Practicum and Roundtable Discussion.

ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) is the first aesthetic injectable approved for reduction of submental fat. In February 2014, an injection practicum was conducted in the anatomy laboratory at the University of Texas Southwestern Medical Center to explore the proper injection technique for ATX-101 and the importance of its appropriate, safe anatomical placement within the submental area. Subsequent to the injection practicum, a structured roundtable discussion was conducted in which potential implications of the various injection protocols evaluated during the practicum were reviewed. Furthermore, the faculty had the opportunity to provide additional perspectives based on their clinical experience with facial injectables and ATX-101 specifically. In this article, the findings from the injection practicum and roundtable discussion are reported.

Overview of ATX-101 (Deoxycholic Acid Injection): A Nonsurgical Approach for Reduction of Submental Fat.

In 2015, ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was approved as a first-in-class injectable drug for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat. ATX-101 has been evaluated in a clinical development program that included 18 Phase 1 to 3 studies supporting the current indication. Since 2007, the toxicity and safety profiles of ATX-101 have been characterized in numerous preclinical studies, its pharmacokinetics, pharmacodynamics, and optimal treatment paradigm have been defined in multiple Phase 1 and 2 studies, and its efficacy and clinical safety have been confirmed in 4 large Phase 3 trials (2 conducted in Europe and 2 in the United States and Canada [REFINE-1 and REFINE-2]). As subcutaneous injection of deoxycholic acid has been shown to cause adipocytolysis, the reduction in submental fat achieved after ATX-101 treatment is expected to be long lasting. This prediction is confirmed by data from long-term follow-up studies of up to 4 years after last treatment with ATX-101, which demonstrate that the treatment response is maintained over time in most subjects. ATX-101 offers a durable, minimally invasive alternative to liposuction and surgery for addressing submental fullness.

Anatomy of the Cervicomental Region: Insights From an Anatomy Laboratory and Roundtable Discussion.

In 2015, ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was approved as a first-in-class injectable drug for reduction of submental fat. Use of a pharmacologic/injectable therapy within the submental region requires a thorough understanding of cervicomental anatomy to ensure proper injection technique and safe administration. To this end, an anatomy laboratory was conducted to review key external landmarks and important internal anatomic structures that characterize the lower face and anterior neck. External landmarks that define the boundaries of the cervicomental and submental regions were identified including the inferior mandibular border, the anterior border of the sternocleidomastoid muscle, the antegonial notch, the submental crease, the thyroid notch, and the hyoid bone. Relevant internal anatomic structures, including preplatysmal submental fat (the target tissue for ATX-101) and the platysma muscle as well as critical neurovascular and glandular tissues were revealed by dissection. Of particular interest was the marginal mandibular branch of the facial nerve because it typically courses along the inferior mandibular border near the proposed treatment area for ATX-101.

Commentary on Overview of ATX-101 (Deoxycholic Acid Injection).

Commentary on Overview of ATX-101 (Deoxycholic Acid Injection).

Special Issue: Deoxycholic Acid Injection Treatment for Reduction of Submental Fat.

Special Issue: Deoxycholic Acid Injection Treatment for Reduction of Submental Fat.

Deoxycholic Acid: A Review in Submental Fat Contouring.

Deoxycholic acid is a secondary bile acid involved in dietary fat emulsification/solubilization that causes adipocyte lysis when injected into subcutaneous fat tissue. A 10mg/mL injectable solution of synthetic deoxycholic acid (Kybella™; Belkyra™) is indicated in various countries, including the USA and several within Europe/the EU, to improve the appearance of moderate to severe convexity or fullness associated with submental fat (SMF) in adults, where it is currently the only approved treatment for fat below the chin. In several phase III trials conducted in this setting, injecting deoxycholic acid 2mg/cm2 into the SMF reduced the convexity/fullness of moderate to severe SMF relative to placebo (with a single treatment comprising up to 50 injections, and up to six treatments given at least 1month apart). These SMF benefits (which were measured subjectively by clinicians and recipients, as well as objectively, 12weeks after the last treatment session) generally occurred without detriment to skin laxity and were largely maintained over extended follow-up (e.g. 2years after treatment). Deoxycholic acid injections are generally well tolerated, with adverse events usually involving the treatment area, being mild to moderate in severity and resolving within approximately one treatment interval. However, not all patients with SMF may be suitable for deoxycholic acid therapy, making patient selection key to achieving desired aesthetic outcomes. Thus, deoxycholic acid injections are an effective and generally well tolerated, minimally invasive option for the treatment of moderate to severe SMF in select adults.