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.

Injection site reactions after dupilumab or tralokinumab for atopic dermatitis.

Background: Injection site reaction (ISR) is a local phenomenon defined as a constellation of symptoms, including swelling, erythema, pruritus, and pain around the site of injection.Objective: ISR is reported as a frequent adverse event after subcutaneous injection (SCI) of several biologics.Methods: We performed an observational real-life study to compare dupilumab and tralokinumab as regards ISR, analysing frequency, duration and intensity of symptoms related to SCI. From January 2023 to June 2023, we enrolled adult patients affected by moderate to severe AD and being on dupilumab or tralokinumab treatment. A 12 items questionnaire was administered to all enrolled patients.Results and conclusions: Three hundred and ninety-two patients were included. ISR was a frequent occurrence in both the treatment groups, with tralokinumab causing ISR more frequently than dupilumab. However, the reactions were generally mild and no patient stopped therapy.

Adverse Events Associated with Hyaluronic Acid Filler Injection for Non-surgical Facial Aesthetics: A Systematic Review of High Level of Evidence Studies.

BACKGROUND: Hyaluronic acid (HA) dermal fillers are widely used in aesthetic medicine. While generally safe, potential complications can arise. OBJECTIVE: This systematic review aims to identify and classify potential complications linked to the use of HA dermal fillers, as informed by high-quality, low-risk-of-bias studies. METHODS: This review follows the Cochrane review standards for clinical systematic reviews. This systematic review analyzed 48 high level of evidence studies on the use of hyaluronic acid (HA) dermal fillers in non-surgical facial aesthetics and the adverse events that occurred.The inclusion criteria were randomized control studies on HA dermal fillers and their complications. Excluded were case reports, case series, observational studies, and other non-randomized research due to their inability to provide generalized conclusions and their inherent publication bias. RESULTS: Adverse events were classified into three categories: expected reactions, product or technique-related adverse events, and severe adverse events. Most adverse events were short-lived injection site reactions, which resolved spontaneously. Specific HA fillers and injection techniques influenced the occurrence of adverse events, which generally resolved within weeks without treatment. Severe adverse events were rare, persisting for months and requiring active medical intervention. DISCUSSION: This classification system can enhance understanding, prevention, and treatment of HA filler complications, and support patient education. The common complications were injection site reactions, with persistent symptoms treated with topical steroids, NSAIDs, or hyaluronidase. Severe complications included severe edema, angioedema and others, often necessitating specific treatments. CONCLUSION: HA dermal fillers are generally safe and effective, with most adverse events being transient and mild to moderate in severity. Severe adverse events, although rare, do occur and are generally non-treatment related. Informed consent, patient education, and professional training are crucial for safe and successful outcomes. Level of Evidence II 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 .

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.

Comparison of the local safety of two multi-component feline vaccines, adjuvanted (1 mL) versus non-adjuvanted at reduced volume (0.5 mL), using computed tomography imaging.

In 2020, a new 0.5 mL presentation of PUREVAX® RCP FeLV was registered and introduced in Europe. The objectives of this study were to investigate the local safety of this non-adjuvanted vaccine at reduced volume by classical methods (clinical examination, histopathology) and to evaluate the suitability of an alternative non-invasive methodology, the computed tomography (CT). For this purpose, the course of local reactions was assessed for 3 months after subcutaneous injection of PUREVAX® RCP FeLV 0.5 mL and compared to an adjuvanted vaccine, LEUCOFELIGEN® FeLV/RCP 1.0 mL. Injection site reactions consisted mainly of swelling reactions, which were more frequent, more pronounced and long-lasting in the adjuvanted vaccine group. Microscopically, in this group, moderate to severe inflammatory reactions were observed on day 7 (D7) and D21 post-injection and still present on D84, while mild inflammatory lesions were observed in the non-adjuvanted vaccine group only on D7 and D21. With the adjuvanted vaccine, inflamed areas were measurable by CT scan in all cats on D7 and D21, whereas they were detected only on D7 and only in 20 % of cats from the non-adjuvanted vaccine group. Besides the higher frequency, the mean inflamed volume was nearly 300 times larger in adjuvanted vaccine group on D7. Using different methodologies, the favorable safety profile of PUREVAX® RCP FeLV 0.5 mL was confirmed. Furthermore, the vaccine is aligned with current vaccination guidelines by inducing less inflammatory reactions, being adjuvant-free and injectable under a reduced volume, thus improving the convenience of administration in recommended sites (eg, legs). CT scan proved to be a suitable non-invasive method for the experimental follow-up of injection site reactions, yielding results consistent with clinical assessment and histopathology on D7 and D21. CT scan substantiated large differences between the investigated vaccines with a more prominent inflammatory reaction after injection of an adjuvanted vaccine.

Adverse reactions following MPox (monkeypox) vaccination: An overview from the Dutch and global adverse event reporting systems.

AIMS: The spreading of MPox (monkeypox) virus led to a vaccination campaign in the Netherlands for individuals at high risk of infection. This overview elucidates the characteristics of the reported adverse events following immunization (AEFI) following active immunization against monkeypox and thereby provides insight on the safety profile in daily practice. METHODS: Data were collected from the spontaneous reporting system of the Netherlands Pharmacovigilance Centre Lareb. Furthermore, the global database of the World Health Organization was consulted on globally reported AEFI following smallpox or monkeypox immunization in 2022. RESULTS: Until 15 November 2022, 148 unique individual case safety reports (ICSRs) regarding monkeypox vaccination were received at Lareb. Two ICSRs reported a serious outcome (1.4%). A total of 2205 ICSRs were received in the global database in 2022, of which 131 reports (5.9%) concerned a serious reaction. Reported AEFI in both databases mainly included injection site reactions and general systemic reactions commonly observed after vaccination. CONCLUSION: The pattern of reported AEFI for monkeypox vaccines both in the Dutch and global ICSR database is generally in accordance with the manufacturer's product information and consists largely of injection site reactions and nonserious AEFI related to systemic reactogenicity.

Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis.

Background: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. Methods: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. Results: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. Conclusions: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. Registration: PROSPERO: CRD42021258012.

Injection Site Reaction to Various Insulins as Type III Allergy With Urticarial Vasculitis in a Patient With Type I Diabetes Mellitus.

ABSTRACT: Injection site reactions are defined as skin reactions at the injection site to drugs administered subcutaneously. Pathophysiologically, these reactions are based on different immunological mechanisms. We report the case of a 49-year-old patient with type 1 diabetes mellitus (first diagnosis in 1994 at the age of 23 years). Continuous subcutaneous insulin infusion using an insulin pump has been used for many years. The patient presented to the department of dermatology with progressive symptoms in the area of the insulin injection sites on the lower abdomen, accompanied by pain, burning, erythema, tenderness, and the formation of subcutaneous nodules. Previous attempts to use different insulins and to change the injection sites did not improve his symptoms. Furthermore, the symptoms appeared within hours after the insulin pump was attached, so that the injection site has to be changed as soon as every 48 hours. No anaphylactic shock was reported at any time. Multiple histological specimens were obtained from an older lesion on the abdomen as well as from test sites after standard allergological tests (prick and intradermal tests) of various insulins. Histologically, these biopsies showed the image of an extensive deep-reaching small vessel vasculitis with the aspect of an urticarial vasculitis and confirmed the diagnosis of an injection-site reaction that can be characterized as a type III hypersensitivity reaction.

Lower injection-site reactions and long-term safety, immunogenicity, and efficacy of etanercept biosimilar YLB113: Results from a post-hoc analysis of a double-blind, randomized, phase III comparative study and its open-label extension in patients with rheumatoid arthritis.

AIM: YLB113 biosimilar was evaluated in an open-label extension single-arm study to assess long-term safety, efficacy, and immunogenicity in patients with rheumatoid arthritis (RA). We also report post-hoc results on the incidence of injection-site reactions (ISRs) and injection-site erythema (ISE) from a phase III study. METHOD: Participants from the phase III, double-blind, randomized, 96 week equivalence study who completed the final visit received 50 mg YLB113 subcutaneously every 2 weeks. Key safety end points were assessed through adverse events (AEs), ISRs, ISE, and anti-drug antibody (ADA) incidence. The efficacy end point was change from baseline in Disease Activity Score 28-joint count (DAS28) over time. RESULTS: Of 201 participants, 184 (91.5%) completed the study. Treatment-emergent AEs were experienced by 93.5% and severe AEs by 10.0% of participants. The discontinuation rate due to AEs was 2.0%. Overall, 20.0% of participants reported an incidence of ISRs throughout the open-label extension study. Two participants developed ADAs, and none developed neutralizing ADAs at any time after study drug administration. The overall DAS28 (mean ± SD) change was 2.22 ± 0.95 at the study transition, 2.10 ± 0.91 at week 72, and 2.06 ± 0.89 at the end of the study. In the post-hoc analysis, YLB113 showed a statistically significant lower incidence of ISRs (10 [3.8%], P < 0.0001) and ISE (5 [1.9%], P < 0.0001) compared with the reference product Enbrel®. CONCLUSION: YLB113 demonstrated long-term safety and sustained efficacy for up to 96 weeks. Patients on YLB113 experienced significantly lower ISRs and ISE in a post-hoc analysis of the phase III study when compared with reference product.

Clinical outcomes after lip injection procedures-Comparison of two hyaluronic acid gel fillers with different product properties.

BACKGROUND: Transient swelling is common after lip injections with hyaluronic acid (HA) based fillers. Swelling and other injection-site reactions may relate to the injection procedure itself, or to gel properties, which differ between fillers due to differences in manufacturing methods. OBJECTIVES: To evaluate safety and effectiveness of lip injections with two HA fillers manufactured using different gel technologies. METHODS: In a study sample of 40 subjects, treatment with two soft tissue filler product (HARK or HAJUS ) was randomly assigned. Subjects were injected with 0.5 cc per upper and lower lip using a standardized injection procedure. Early-onset adverse events (AEs) were assessed by evaluation up to Day 14. Aesthetic improvement, subject satisfaction, and AEs post-Day 14 were assessed up to 24 weeks. RESULTS: In subjects treated with HARK , the intensity of early onset swelling, erythema, and pain/tenderness was lower than in subjects treated with HAJUS . Aesthetic improvement was achieved in both groups, and most subjects were satisfied with the appearance of their lips. Treatment-related AEs post-Day 14 mostly related to the implant site; most were mild-to-moderate, and none were serious. CONCLUSIONS: The intensity of early-onset swelling, and other injection-site reactions was lower in subjects treated with HARK than in subjects treated with HAJUS . Since both the injection volume and injection procedure were standardized, the difference in local tolerability between the two HA fillers may relate to differences in gel properties. Aesthetic improvement, subject satisfaction, and AE profiles post-Day 14, however, were similar between filler groups.

Prevalence of pain and fear as barriers to vaccination in children - Systematic review and meta-analysis.

BACKGROUND: Injection-related pain and fear are common adverse reactions in children undergoing vaccination and influence vaccine acceptance. Despite the large body of literature on sources of vaccine non-compliance, there is no estimate of the prevalence of pain and fear as contributing factors. The objective was to estimate the prevalence of injection pain or fear of needles as barriers to childhood (i.e., 0-18 years) vaccination. METHODS: Four databases were searched from inception for relevant English and French articles until August 2021. In addition, the references of recent systematic reviews and all articles included in the review were hand searched. Article screening and data extractions were performed in duplicate. Studies were included if they reported on injection-related pain or fear of needles in children (0-18 years) using a checklist/closed-ended question(s). Results were stratified by respondent (parents or children), type of pediatric population (general or under-vaccinated), and relative importance of barrier (pain or needle fear as primary reason or any reason for under-vaccination). Prevalence rates of pain or needle fear were combined using a random effects model. Quality of included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for prevalence data. Quality across studies was assessed using GRADE. RESULTS: There were 26 studies with 45 prevalence estimates published between 1995 and 2021. For parent reports (of children) and children self-reported reasons for non-compliance, prevalence rates of pain or needle fear ranged from 5 to 13% in a general population and 8 to 28% in an under-vaccinated population, with a substantial variation in the prevalence estimates. There was no difference between category of respondent or relative importance on pain or needle fear prevalence rate. A regression model demonstrated an overall prevalence rate of pain or needle fear as an obstacle to vaccination of 8% in the general population and 18.3% in the under-vaccinated population. All evidence was very low in quality. CONCLUSION: This is the first review to systematically quantify the prevalence and therefore, importance, of pain and needle fear as obstacles to vaccination in children around the world. Pain from injection or fear of needles were demonstrated to be sufficiently prevalent as barriers to vaccination in children to warrant attention. Addressing pain and fear has the potential to significantly improve vaccination acceptance.

Restylane Lyft for Aesthetic Shaping of the Nasal Dorsum and Radix: A Randomized, No-Treatment Control, Multicenter Study.

BACKGROUND: Hyaluronic acid fillers are widely used in nonsurgical rhinoplasty. METHODS: The authors performed a no-treatment control, multicenter, 12-month follow-up study to evaluate efficacy and safety of Restylane Lyft (Galderma, Uppsala, Sweden) in shaping the nasal dorsum and radix. Assignment to Restylane Lyft or no-treatment control was randomized (3:1). The Restylane Lyft group received a maximum of 1 ml of Restylane Lyft on day 1; the control group was offered a maximum of 1 ml of Restylane Lyft at month 6. Both groups were offered re-treatment (a maximum of 0.5 ml of Restylane Lyft) at month 12. Outcome assessments included blinded evaluation of three-dimensional photography measurements of change in volume (primary endpoint; month 6) and elevation of the nasal dorsum and radix, aesthetic improvement, adverse events, and diary-reported injection-site reactions. RESULTS: One hundred thirty-two Chinese subjects were enrolled. The Restylane Lyft group had a greater increase in volume of the nasal dorsum and radix than the no-treatment control (mean difference at month 6, 0.71 ml; 95 percent confidence interval, 0.59 to 0.83 ml; p < 0.001). Restylane Lyft was also more effective than no-treatment control in achieving an elevation of the nasal dorsum and radix. The increase in volume and elevation persisted up to 12 months after injection and was supported by clinical assessments of aesthetic improvement. Treatment-related adverse events were mild to moderate, nonserious, and resolved during the study. Injection-site reactions were mostly mild to moderate and resolved within 1 week. CONCLUSION: Restylane Lyft injection was effective for aesthetic shaping of the nasal dorsum and radix and achieved aesthetic improvement for up to 12 months with an acceptable safety profile. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Cutaneous adverse events following 771 doses of the inactivated and mRNA COVID-19 vaccines: A survey study among health care providers.

INTRODUCTION: As Coronavirus disease 19 (COVID-19) still continues to affect humanity worldwide, different types of COVID-19 vaccines are being administered to maintain immunization against COVID-19. As both the inactivated and mRNA vaccines are now being applied prevalently, systemic adverse events along with cutaneous side effects are frequently being reported in the literature. AIM: In our study, we aimed to determine the cutaneous adverse effects of the inactivated (Sinovac-CoronaVac) and mRNA (Pfizer-BioNTech) vaccines in healthcare providers in a tertiary referral hospital. METHODS: A web-based survey consisting of 26 questions related to the systemic and cutaneous side effects of the inactivated and mRNA COVID-19 vaccines, was formed. The online questionnaire was spread among the healthcare professionals working in a tertiary referral hospital via common instant messaging groups and e-mail. FINDINGS: A total number of 234 participants were included in the study. One hundred fifty-seven were female whereas 77 were male. The mean age was 31.51 years. Eighty-nine respondents reported to have at least one cutaneous side effect after COVID-19 vaccination. Most commonly observed cutaneous side effects were local injection site reactions. Pfizer-BioNTech vaccine at the first and second doses, was shown to have statistically significantly higher rates of systemic and cutaneous adverse events compared to the Sinovac-CoronaVac vaccine. RESULTS: Our study shows that both inactivated and mRNA COVID-19 vaccines are associated with transient local injection site reactions, no severe systemic or cutaneous adverse events were observed in our study population.

Evaluation of the long-term safety and biodegradability of hyaluronic acid dermal fillers (YVOIRE® ) for the correction of nasolabial folds: Two multicenter, prospective, observational cohort studies.

BACKGROUND: The therapeutic effects of hyaluronic acid dermal fillers to correct facial wrinkles and folds usually last up to 6-12 months. Few studies have evaluated their long-term safety. AIMS: To evaluate the long-term safety and biodegradability of two hyaluronic acid dermal fillers (YVOIRE® classic s and YVOIRE® volume s) for the correction of nasolabial folds (NLFs) in two prospective, observational studies. METHODS: Subjects scheduled to receive the injections of YVOIRE® classic s (N = 503) or YVOIRE® volume s (N = 503) at NLFs were followed up until complete clinical biodegradation, defined as a change in Wrinkle Severity Rating Scale (WSRS) score of ≥0 from baseline. The primary biodegradation endpoint was the proportion of subjects with complete clinical biodegradation during or after the 104-week post-treatment period. RESULTS: Complete clinical biodegradation was observed in 93.5% [95% CI 91.0%-95.5%] of 494 assessable YVOIRE® classic s recipients and 98.5% [95% CI 97.0%-99.4%] of 469 YVOIRE® volume s recipients during the 104-week post-treatment period. In most subjects, complete clinical biodegradation was observed within 52 weeks of the last treatment. Treatment-related adverse events (AEs) (mostly mild local injection-site reactions) occurred within 52 weeks post-treatment, in 68.2% and 75.0% of YVOIRE® classic s and YVOIRE® volume s recipients, respectively. During the 12 to 18 months after YVOIRE® volume s injection, 0.6% of subjects had treatment-related AEs (local injection-site reactions). No treatment-related AEs occurred 12 to 24 months after YVOIRE® classic s injection. CONCLUSIONS: YVOIRE® classic s and YVOIRE® volume s can be safely used to correct NLFs. Total clinical biodegradation tends to occur within 12 months of injection.

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.

Reactogenicity and immunogenicity of heterologous prime-boost immunization with COVID-19 vaccine.

BACKGROUND: The objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies. METHODS: PubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted. RESULTS: Nineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant. CONCLUSIONS: The current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.