One-Year Safety Evaluation of New Hyaluronic Acid Fillers (YYS Series): A Prospective, Multicenter, Observational Study.

BACKGROUND: With the continuous increasing availability of new filler products, each hyaluronic acid filler brand has distinctive pharmacokinetics, which may be associated with different complications. Therefore, the long-term safety of new generations of fillers should be evaluated. OBJECTIVE: This prospective, multicenter, observational, postmarketing study ( ClinicalTrials.gov identifier: NCT04738019) aimed to investigate the incidence of delayed-onset nodules and adverse reactions after the injection of new hyaluronic acid fillers (YYS series) into the facial skin. METHODS: Subjects scheduled to receive an injection YYS series filler were followed up for 52 weeks. The authors aimed to determine the incidence of a self-reported delayed-onset nodule-a visible or palpable nodule or mass at the injection site that was detected beyond the 14th day following the injection-during the 1-year follow-up period. RESULTS: Among the 1,022 subjects who received an injection of the YYS series, the incidences of delayed-onset nodules were 0% for YYS 360, YYS 540, and YYS 720. A 0.21% incidence (1 delayed hypersensitivity reaction) of a delayed-onset adverse reaction was noted for YYS 720, although none were reported for YYS 360 and YYS 540. CONCLUSION: In this study, a notably low frequency of adverse reactions associated with the YYS series was observed.

The Use of Facial Fillers in Clinical Practice: The Level of Patient Satisfaction and an Overview of Common Clinical Complications. / [Artículo traducido] Uso de rellenos faciales en la práctica clínica: nivel de satisfacción del paciente y visión general de las complicaciones clínicas comunes.

BACKGROUND: Patient esthetic satisfaction following facial fillers is an essential topic that should be studied as the number of individuals seeking treatment increases. The face is an essential component of the human body that is frequently associated with beauty, youthfulness, and health. Individuals may seek facial augmentation with fillers for a variety of reasons, such as congenital, acquired by means of aging or disease, or current aesthetic trends. OBJECTIVE: The aim is to assess patient's aesthetic satisfaction and description of common clinical complications in relation to the facial filler injections. METHOD: A cross sectional survey using a questionnaire derived from the global aesthetic improvement scale and WHO quality of life scale, convenience sampling was used to recruit patients attending cosmetic clinics, descriptive analysis and Chi-square methods were used to analyze the data. RESULTS: In the study, 500 female participants, with an average age of 28.48 years, were included. Over 90% reported improvement after filler treatment, ranging from improved to very much improved. A statistically significant correlation was observed between patient satisfaction and the number of filler treatments and the anatomical injection site. However, no statistically significant correlation was found when considering age groups. Local side effects, such as swelling and redness at the injection site, were common but generally mild and of short duration. CONCLUSION: Although the satisfaction level is currently high, practitioners in the field need to pay more attention to this important outcome, since understanding the patient's motivation and expectation before proceeding with the procedure is very important and can contribute significantly in determining patient satisfaction with the result.

A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

Incidence and Characteristics of Delayed Injection Site Reaction to the mRNA-1273 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine (Moderna) in a Cohort of Hospital Employees.

BACKGROUND: mRNA SARS-CoV-2 vaccines are administered to 2 million individuals per day in the United States under US Food and Drug Administration emergency use authorization. METHODS: Observational cohort study of hospital employees who received their first SARS-CoV-2 mRNA vaccination between 14 December 2020 and 8 January 2021, including employees who reported onset of an injection site reaction ≥48 hours after administration of their first or second dose to an employee hotline. RESULTS: Thirteen female employees who received the mRNA-1273 vaccine (Moderna) during the first 3 weeks of the SARS-CoV-2 vaccine rollout at San Francisco General Hospital reported a pruritic rash at the injection site appearing 3 -9 days after receipt of their initial dose. Five had milder or similar reactions with earlier onset after the second dose. One additional female employee reported this delayed reaction only after the second dose. None reported serious adverse events or had symptoms severe enough to seek medical attention. These cases represented 1.1% of the 1275 female employees who received their first mRNA-1273 dose and 2.0% of the 557 who were aged 31 -45 years during this initial vaccine rollout. None of 675 males who initiated mRNA-1273 or 3612 employees of any sex who initiated BNT162b (Pfizer) vaccination during this period reported delayed-onset reactions. CONCLUSIONS: These results suggest that delayed-onset, injection site pruritic rashes after mRNA-1273 SARS-CoV-2 vaccine administration, lasting up to 1 week, occur commonly in females, do not lead to serious sequela, and should not deter receipt of the second vaccine dose.

Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). METHODS: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. RESULTS: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. CONCLUSIONS: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.

Cutaneous adverse reactions to coronavirus vaccines: A Saudi nationwide study.

The coronavirus vaccine was developed to help overcome the COVID-19 crisis. This study aimed to identify the cutaneous side effects secondary to Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines in the general population of Saudi Arabia and to list the risk factors for the development of cutaneous side effects. This cross-sectional study was conducted in 2021, self-administered surveys were distributed electronically through social media, and telephonic interviews were conducted with a sample size of 1000 participants. Data analysis was performed using Statistical Package for the Social Sciences. A total of 1021 patients (229 male and 722 female) aged 12 years or older were included. While 833 participants were medically free, 188 had chronic illnesses. While 802 participants were not taking any medications, 219 were taking medications regularly. Oxford-Astra Zeneca and Pfizer BioNTech vaccines were administered to 319 and 702 participants, respectively. One-hundred and twenty-five participants previously had COVID-19 infection and 407 were exposed to a PCR positive case of COVID. Six hundred and fifty-nine patients (64.5%) reported experiencing injection site reactions: 606 (59.4%) had injection site pain, 168 (16.5%) had injection site swelling, and 107 (10.5%) had injection site redness. Only 51 patients (5%) experienced cutaneous side effects after injection. A significant association was found between chronic illnesses and cutaneous side effects post-vaccine (9% vs. 4.1%; p value = 0.005). Patients on medications showed a higher rate of symptoms (8.2% vs. 4.1%; p value = 0.005). Age, gender, vaccine types, and history of COVID-19 infection were not significantly associated with cutaneous side effects post-vaccine.

Immunogenicity and skin clearance recapture in clinical studies of brodalumab.

BACKGROUND: Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy. OBJECTIVE: To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment. METHODS: Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed. RESULTS: Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab. LIMITATIONS: Retreatment could be assessed in only 1 phase 3 brodalumab study. CONCLUSION: Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan.

BACKGROUND: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants. METHODS: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10). All subjects received a 3-dose primary vaccination series and a booster. Non-inferiority (Group A versus Group B) was tested post-primary series and subsequent post hoc analyses were performed for anti-Hib. Safety was assessed by parental reports. RESULTS: Non-inferiority for SC administration of Group A versus Group B for the primary series was demonstrated for antibody responses to all antigens except Hib using the threshold of 1.0 µg/mL. Post hoc analyses for anti-Hib demonstrated non-inferiority for the primary series response using 0.15 µg/mL, and for pre-booster antibody persistence and the booster response using 0.15 µg/mL and 1.0 µg/mL. The immune response was similar for each antigen following SC or IM administration. There were no safety concerns in any group, and a lower incidence of injection sites for the IM route was observed as expected. CONCLUSIONS: These data show the good immunogenicity and safety profile of the DTaP-IPV/Hib vaccine as a 3-dose infant primary series followed by a booster in the second year of life in Japan.

Safety and Tolerability of Rapid Administration Undiluted Levetiracetam.

BACKGROUND/OBJECTIVE: Levetiracetam (LEV) is an antiepileptic drug used widely in patients with a favorable safety profile. Studies evaluating the safety and efficacy of intravenous (IV) LEV included volumes of at least 100 mL. Minimally diluted doses administered over 5-6 min were found to be both safe and effective. Given the complexities of admixing, this practice can be impractical and result in delays in antiepileptic therapy. This study aimed to retrospectively review the safety and tolerability of rapid administration of undiluted LEV doses ≤ 1000 mg. METHODS: This was a retrospective study evaluating adverse drug reactions associated with undiluted LEV from January 1, 2018-June 1, 2018. Patients were included if they received at least one dose of undiluted LEV and were ≥ 18 years old. Safety endpoints were reviewed and collected from the time administration until hospital discharge. Endpoints included injection site pain and discomfort, injection site erythema, extravasation, IV line replacement, and any documented adverse effect leading to IV LEV discontinuation. Descriptive statistics were used to analyze the data. RESULTS: A total of 199 patients were included in the study totaling 1626 doses of LEV. Most patients were administered LEV 1000 mg (60.8%), through a peripheral line (64.3%), and were prescribed LEV for seizure prophylaxis (58.3%). Patients received a mean of 8.1 ± 8 doses for a mean duration of therapy of 5 ± 4.5 days. About 98.5% of patients did not experience an adverse effect, whereas 1.5% of patients experienced agitation, delirium, confusion, and/or lethargy, which is well known to LEV therapy. CONCLUSIONS: Rapid administration of undiluted LEV doses ≤ 1000 mg were well tolerated with no concentration-related side effects. Further prospective research is needed to confirm this observation as well as the safety of higher doses.

Safety and Tolerability of Accelerated Infliximab Infusions in Patients With Inflammatory Bowel Disease.

INTRODUCTION: Infliximab for inflammatory bowel disease (IBD) is FDA-approved to be administered 2 h or more. We adopted a new protocol to infuse infliximab over 1 h and in this study, we aimed to determine the safety of a 1-h infusion. METHODS: This retrospective cohort included adult IBD patients who received infliximab between June and December 2017 and compared reaction rates of 1-h maintenance infusions to that of 2-h maintenance infusions. RESULTS: A total of 551 infusions were administered to 179 patients. The infusion groups demonstrated no significant differences in reaction rates. CONCLUSIONS: Infliximab infusion over 1 h is well-tolerated.

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis.

INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

Unintentional Epinephrine Auto-injector Injuries: A National Poison Center Observational Study.

BACKGROUND: Epinephrine is the only first-line therapeutic agent used to treat life-threatening anaphylaxis. Epinephrine auto-injectors are commonly carried by patients at risk for anaphylaxis, and reported cases of unintentional auto-injector injury have increased over the last decade. Modifications of existing designs and release of a new style of auto-injector are intended to reduce epinephrine auto-injector misuse. STUDY QUESTION: The aim of the study was to characterize reported cases of unintentional epinephrine auto-injector exposures from 2013 to 2014 and compare demographics, auto-injector model, and anatomical site of such exposures. METHODS: The American Association of Poison Control Center's National Poison Data System was searched from January 1, 2013, to December 31, 2014, for cases of unintentional epinephrine auto-injector exposures. Anatomical site data were obtained from all cases reported to the Virginia Poison Center and participating regional poison center for Auvi-Q cases. RESULTS: A total of 6806 cases of unintentional epinephrine auto-injector exposures were reported to US Poison Centers in 2013 and 2014. Of these cases, 3933 occurred with EpiPen, 2829 with EpiPen Jr, 44 with Auvi-Q, and no case reported of Adrenaclick. The most common site of unintentional injection for traditional epinephrine auto-injectors was the digit or thumb, with 58% of cases for EpiPen and 39% of cases with EpiPen Jr. With Auvi-Q, the most common site was the leg (78% of cases). CONCLUSIONS: The number of unintentional epinephrine auto-injector cases reported to American Poison Centers in 2013-2014 has increased compared with previous data. Most EpiPen exposures were in the digits, whereas Auvi-Q was most frequently in the leg. Because of the limitations of Poison Center data, more research is needed to identify incidence of unintentional exposures and the effectiveness of epinephrine auto-injector redesign.

Safety of live attenuated varicella-zoster vaccine in patients with underlying illnesses compared with healthy adults: a prospective cohort study.

BACKGROUND: In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster. METHODS: A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated. RESULTS: During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%). CONCLUSIONS: The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults. TRIAL REGISTRATION: The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

Premedication with intravenous steroids does not influence the incidence of infusion reactions following infliximab infusions in pediatric inflammatory bowel disease patients-a case-control study.

PURPOSE: Infusion reactions (IR) are commonly described side effects of infliximab (IFX) infusions, often leading to discontinuation of IFX. This study aimed to investigate the influence of steroid premedication (PM) on incidence of IR in pediatric inflammatory bowel disease (PIBD) patients receiving IFX. METHODS: A case-control study in two tertiary centers in Amsterdam, The Netherlands, including PIBD patients receiving IFX. PM with steroids was part of standard care in one center (PM+) but not in the other center (PM-). Acute IR were divided into mild/severe reactions and in grade 1/2/3/4 for detailed exploration. Differences between subgroups were assessed with the T or chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. RESULTS: We included 226 patients (91 PM+, 50% male, mean age at onset of IBD 12.7 years), receiving 3433 infusions. There was no difference between the PM+ and PM- subgroups in incidence of IR (14.3% vs. 17.0% of patients, p = 0.58) and in percentage of infusions followed by IR (1.4% in both subgroups). The OR of developing IR when using PM was 1.06 (95% CI 0.49-2.27, p = 0.89), and the OR of developing a grade 3 or 4 IR when using PM was 0.90 (95% CI 0.24-3.39, p = 0.88) when correcting for co-medication usage. CONCLUSION: The incidence of IR was low, and premedication with steroids did not decrease the incidence of IR in this cohort of PIBD patients receiving IFX. Our results indicate that PM with steroids is not indicated in PIBD to prevent IR.

Safety of a quadrivalent meningococcal conjugate vaccine in healthy subjects aged 9 months to 55 years in Vietnam.

PURPOSE: Meningococcal disease is a major global health concern due to its severe and sudden clinical manifestations, devastating long-term sequelae, and predominance in younger age groups. This study evaluated the safety of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D; Menactra) in participants aged 9 months to 55 years in Vietnam. METHODS: This was an open-label, single-arm study conducted between June and December 2016. Participants received one 0.5-mL dose of the vaccine, and those aged 9 to 23 months received a second 0.5-mL dose 3 months later. Participants (or their parents or legal guardians) reported adverse events during the 28 days after each dose. RESULTS: The study included 112 participants aged 9 to 23 months and 112 participants aged 2 to 55 years. Of these 224 participants, 100 (44.6%) had one or more solicited reactions within 7 days following any MenACWY-D dose, mostly injection site pain, lost appetite (in 9 to 23-month-olds), and malaise (in 2 to 55-year-olds). Most solicited reactions were of mild or moderate intensity and resolved within 3 days. Five participants had unsolicited adverse reactions (ARs), two of which (tonsillitis and febrile convulsion), in 9 to 23-month-olds, were considered by the investigator as serious adverse events related to the vaccine. No immediate unsolicited ARs, severe unsolicited nonserious ARs, or unsolicited injection site reactions were reported, and both participants who experienced vaccine-related serious adverse events recovered. CONCLUSION: Consistent with studies in other countries, MenACWY-D had an acceptable safety profile in individuals from Vietnam aged 9 months to 55 years (WHO Universal Trial Number: U1111-1143-9207).

Incidence and Management of Infusion Reactions to Infliximab in an Alternate Care Setting.

BACKGROUND: Infliximab is a chimeric anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody that ameliorates inflammation when it binds to and neutralizes TNF-α. It is often used in patients with Crohn's disease and ulcerative colitis to reduce the severity of disease symptoms and induce disease remission. Infusions are generally administered in the hospital setting due to concerns over patient safety, and limited data exist regarding the incidence and management of infusion reactions (IRs) in an alternate care setting without direct physician oversight. AIMS: The aim of this study was to evaluate the incidence of IRs following administration of infliximab and associated management approaches in an alternate care setting. METHODS: A retrospective chart review of 796 patients with Crohn's disease or ulcerative colitis that received a combined 5581 infusions with one home infusion provider between January 2014 and November 2016 was conducted. Timing, severity, management approach, and outcomes of IRs were abstracted and analyzed. RESULTS: A total of 109 infusion reactions (2.0% of all infusions) were recorded in 62 patients (7.8% of all patients). The majority of these reactions were acute and mild or moderate in severity and resolved with rate adjustments and/or medication. Emergency room visits were required in 0.1% of all infusions, and 0.3% of all infusions were not completed due to a reaction. CONCLUSIONS: IRs to infliximab were uncommon and mostly mild or moderate in severity. Resolution of the IR and continuation of therapy was achieved in most patients through a management approach that included prompt recognition and initial treatment via rate adjustments and medications according to physician's orders.

Injection site reactions after long-term subcutaneous delivery of drisapersen: a retrospective study.

A retrospective study in which we reviewed the hospital files of a subset of 7 patients with Duchenne muscular dystrophy participating in the open-label phase I/II PRO051-02 study in Leuven. The objective of this study was to describe in detail the injection site reactions in these children treated with drisapersen (PRO-051), a 2'-O-methyl phosphorothioate RNA antisense oligonucleotide, that induces exon 51 skipping in Duchenne muscular dystrophy. Antisense oligonucleotides, restoring the reading frame by skipping of exons, have become a potential treatment of Duchenne muscular dystrophy and other monogenetic diseases. Erythema followed by hyperpigmentation, fibrosis, and calcification were seen at the injection sites in all children. Ulcerations, which were difficult to heal, occurred in 5 of 7 children. Progression still occurred after switching to intravenous administration of drisapersen or even after stopping therapy. Systemic reactions included a reversible proteinuria and α1-microglobulinuria. Moreover, hypotrichosis was a common feature.Conclusion: Subcutaneous administration of drisapersen causes severe and progressive injection site effects. What is known: • Antisense oligonucleotides offer the possibility to convert Duchenne muscular dystrophy to the less severe Becker type. This can potentially be achieved by targeting and skipping specific exons of the Duchenne muscular dystrophy gene to restore the disrupted reading frame and to induce the production of a semi functional dystrophin protein. • Drisapersen is such an antisense oligonucleotides which can be administered subcutaneously. Its use has been tested extensively in the escalating dose pilot study (PRO051-02). What is new: • This report describes the injection site reactions caused by this type of agent in detail which has never been done before. We therefore reviewed the hospital files of 7 patients with Duchenne muscular dystrophy participating in the phase I/II open-label, escalating dose pilot study (PRO051-02) with drisapersen. • Severe side effects starting with erythema, hyperpigmentation, and later fibrosis, calcification, and difficult to treat ulcerations developed in all patients, and these continued to progress even after cessation of drisapersen. We discuss some possible underlying mechanisms. The exact mechanism however is still not known.

Marginalized models for right-truncated and interval-censored time-to-event data.

Analysis of clustered data is often performed using random effects regression models. In such conditional models, a cluster-specific random effect is often introduced into the linear predictor function. Parameter interpretation of the covariate effects is then conditioned on the random effects, leading to a subject-specific interpretation of the regression parameters. Recently, Marginalized Multilevel Models (MMM) and the Bridge distribution models have been proposed as a unified approach, which allows one to capture the within-cluster correlations by specifying random effects while still allowing for marginal parameter interpretation. In this paper, we investigate these two approaches, and the conditional Generalized Linear Mixed Model (GLMM), in the context of right-truncated, interval-censored time-to-event data, further characterized by clustering and additional overdispersion. While these models have been applied in literature to model the mean, here we extend their application to modeling the hazard function for the survival endpoints. The models are applied to analyze data from the HET-CAMVT experiment which was designed to assess the potential of a compound to cause injection site reaction. Results show that the MMM and Bridge distribution approaches are useful when interest is in the marginal interpretation of the covariate effects.

Safe, Effective Chin and Jaw Restoration With VYC-25L Hyaluronic Acid Injectable Gel.

BACKGROUND: VYC-25L, a hyaluronic acid soft-tissue filler with lidocaine, is designed to restore and create facial volume in the chin and jaw. OBJECTIVE: To evaluate the safety and effectiveness of VYC-25L in subjects with chin retrusion. METHODS: Adults with chin retrusion (145°-165° glabella-subnasale-pogonion facial angle) were randomized (3:1) to receive VYC-25L in the chin/jaw at study onset (treatment group) or 3 months later (control group). Primary effectiveness end point was mean change in facial angle from baseline at Month 3. Safety assessments included injection site responses (ISRs), recorded in a subject diary, and adverse events (AEs). RESULTS: VYC-25L was administered to 119 subjects (treatment group: n = 90; control group: n = 29). Mean change in facial angle from baseline at Month 3 was significantly greater in the treatment versus control group (difference: 2.51°; p < .0001). Effectiveness was also demonstrated by the proportion of subjects with improved/much improved Global Aesthetic Improvement Scale scores and responses on FACE-Q Satisfaction and Psychological Well-Being Scales. Treatment benefit remained evident at Month 12. Common ISRs were firmness (95.8%), tenderness (95.8%), and swelling (91.6%). No serious treatment-related AEs were reported. CONCLUSION: VYC-25L significantly improved glabella-subnasale-pogonion facial angle and was generally safe and well tolerated.

Real-World Experience With 100 Consecutive Patients Undergoing Neck Contouring With ATX-101 (Deoxycholic Acid): An Updated Report With A 2-Year Analysis.

BACKGROUND: Deoxycholic acid (DCA; ATX-101) injection was approved for the treatment of mild-to-moderate convexity associated with submental fat in 2015. OBJECTIVE: To evaluate the experience with DCA injections in a clinical practice setting. MATERIALS AND METHODS: This ongoing, prospective, single-center, single-arm, observational study evaluated 100 consecutive patients treated with subcutaneous DCA (2 mg/cm) injections (maximum 6 sessions at ≥1-month intervals). Treatment response was assessed using the clinician-reported submental fat rating scale (CR-SMFRS) and confirmed by independent physician review of photographs at 1 and 5 to 7 weeks after treatment. RESULTS: Since the previous published report, 17 patients have undergone additional treatment sessions, with a total of 100 patients having undergone 195 treatment sessions: 41, 36, 14, 6, 2, and 1 patient underwent 1, 2, 3, 4, 5, and 6 sessions, respectively. Overall, 91.7% of patients in the single treatment session group and 100% in the multiple treatment session group had an improvement of ≥1 point on the CR-SMFRS. The mean (SD) duration of local edema, numbness, and tenderness after treatment was 7.1 (5.1), 27.9 (11.3), and 3.5 (3.5) days, respectively. CONCLUSION: Deoxycholic acid injections were generally well tolerated, and ≥2 treatment sessions were required to achieve the desired aesthetic goal in a private practice setting.