Included Injection Site Reactions Research Articles

Once-weekly Insulin Icodec – An emerging treatment option for type 2 Diabetes

The treatment of diabetes often necessitates the administration of exogenous insulin, but research shows that patients are less compliant with administering insulin daily. The main hurdle comprises the frequent need for insulin injections, anxiety linked with self-injection, and the intricacy of timing one’s insulin administration. Considering that recurrent insulin injections can result in resistance, administering once weekly insulin icodec instead of once daily glargine U100 can be one of the suitable alternatives to handle this problem. Insulin codec, a basal insulin analogue administered subcutaneously with a half-life of approximately one week, takes three to four weeks to reach a steady state and has been proven efficacious in patients with type 2 diabetes. [1] A few months ago, the results of the 78-week randomized clinical trial were published. The trial enrolled 492 patients, each in the icodec and glargine U100 groups, who were not treated with insulin previously. The levels of glycated haemoglobin (HbA1c) play a very important role in the management of type 2 diabetes mellitus, and this study showed a significant decrease in HbA1c levels with icodec as compared to the patients who received once-daily glargine. For people taking non-insulin glucose-lowering agents such as glucagon-like peptide-1 agonists and sodium-glucose cotransporters-2 (SGLT2) inhibitors, the concurrent use of icodec was more effective than glargine U100. [2] However, it is important to mention that insulin icodec was associated with slight weight gain. Regarding hypoglycemic episodes, icodec was linked with level 1 hypoglycemia but surprisingly played a protective level against level 2 or 3 nocturnal hypoglycemia. So, overall, the risk of serious hypoglycemic events was not a major concern with this therapy. Other adverse events, including injection site reactions and hypersensitivity reactions, were not reported. [3] Another interesting observation was the reduction in bolus insulin need over time as compared to glargine U100. Once weekly insulin administration showed such better basal insulin coverage that the requirement of bolus insulin was reduced making it a better option altogether. [4] The growing evidence suggests that insulin icodec can prove effective in the management of type 2 diabetes. Once-weekly administration can improve patient compliance while leading to better glycemic control and a greater time in range (TIR) with no severe hypoglycemic risk as compared to once-daily glargine. Taking into consideration the above facts, it is vital to give insulin icodec a chance in treatment of diabetes mellitus for the betterment of patient care. [5]

SV-BR-1-GM after progression on ADC in patients with metastatic breast cancer.

1087 Background: Antibody-drug conjugate (ADC) sequencing raises concerns of cross-resistance due to their shared targets and cytotoxic payloads. Consequently, treatments after ADCs in heavily pretreated MBC is uncertain. SV-BR-1-GM, a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line, has emerged as a post ADC solution (1) based on a different MOA. We now report the results of SV-BR-1-GM in ADC treated patients. Methods: Post-hoc analysis of an ongoing randomized Phase 2 censored to the data-cut date prior to data lock. Bria-IMT (~20x106 SV-BR-1-GM cells, intradermally 48-72 hours after ctx (300 mg/m2), followed by interferon-alpha 2 days later) administered q3wks with a checkpoint inhibitor (CPI). Adverse events were classified according to their severity and relationship to treatment regimen. Results: Among 54 advanced MBC patients randomized, 23 who failed prior ADC therapy were identified. All were heavily pretreated (median 6 prior lines, range 3 – 13). Median age 62 (41-83). 14 pts had HR+/HER2-, 5 TNBC, and 2 HR+/HER2+ MBC. The remaining were HR-/HER2+ or HR-/HER2 low. 8 pts received > 1 ADC. Prior ADCs included: 4 ado-trastuzumab emtansine, 14 trastuzumab deruxtecan, 13 sacituzumab govitecan. 7 pts had also received ≥ 1 prior CPI line. To date, pts received a median 3 cycles of Bria-IMT™ + CPI (2-8). Kaplan-Meier analysis revealed a median OS of 42 weeks with survival of 69% at 6 months. The subset experienced a median PFS of 74 days with 40% of pts demonstrating a Bria-IMT PFS (PFS2) similar to or > their prior line PFS (PFS1). 39% of pts experienced a PFS2 ≥ their most recent line of ADC PFS. The disease control rate was 40% among evaluable pts. 43% of pts had a reduction in cancer-associated macrophage-like cell (CAML) levels; median reduction was 36% (22-98%) after 1 cycle. There were no toxicity-related treatment discontinuations. 43% (10/23) reported grade 3 or 4 AEs, independent of study drug causality. AEs included injection site reaction (39%), fatigue (26%), and nausea/vomiting (43%), mostly mild to moderate. One case of elevated lipase was the most clinically significant grade 4 AE. No interstitial lung disease (ILD) was reported. Conclusions: This subset analysis of the Bria-IMT regimen in ADC refractory MBC patients suggests a potential clinical benefit and treatment option for this patient population. The absence of serious AEs, notably interstitial lung disease (ILD), and no toxicity-related treatment discontinuations, underscores the regimen's favorable safety profile. Future studies are warranted to confirm these results and explore the potential of Bria-IMT™ in broad clinical settings of heavily pretreated contemporary MBC patients. 1. Kamaraju 2024 AACR. Clinical trial information: NCT03328026 .

Multiple Mucosal Ulcers Induced by Ixekizumab: A Case Report.

Ixekizumab, an interleukin (IL)-17A inhibitor, exerts its therapeutic effects in psoriasis by inhibiting the interleukin (IL)-17 signaling pathway. Common adverse reactions to ixekizumab include injection site reactions and upper respiratory tract infections (URIs), while occurrences of inflammatory bowel disease (IBD) and multiple mucosal ulcers are infrequent. We present a case of a 51-year-old man who developed multiple mucosal ulcers after ixekizumab treatment. A 51-year-old man presented to our hospital with a 1-month history of pharyngalgia. The flexible laryngoscope displayed mild hyperemia in the pharyngeal mucosa and tonsils, redness and swelling of the epiglottis, as well as multiple ulcers in the oral cavity, uvula, and epiglottis. These ulcers did not improve with conventional treatment. Upon evaluation, the ulcers were an immune-related adverse event induced by ixekizumab. Consequently, a decision was made to discontinue the drug and initiate a therapeutic regimen including corticosteroids and thalidomide. Eventually, the patient's symptoms abated. Biologics are now becoming increasingly popular in psoriasis. It is vital for clinicians to be aware of this potential adverse event and to identify and intervene early to alleviate patients' suffering.

Abstract CT206: Efficacy and safety of SV-BR-1-GM after progression on ADC in metastatic breast cancer patients

Abstract Background: Antibody-drug conjugate (ADC) sequencing raises concerns of cross-resistance due to their shared cytotoxic payloads. Consequently, there is a pressing need for treatments after ADCs, especially in heavily pretreated patients. Immunization with irradiated SV-BR-1-GM, a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line, has emerged as a potential post ADC solution based on a different mechanism of action. This retrospective analysis aims to assess the overall efficacy and safety of SV-BR-1-GM in a subset of ADC treated patients. Methods: Post-hoc subset analysis of the ongoing randomized Phase 2 study identified 23 advanced MBC patients who failed prior ADC therapy. Bria-IMT™ (irradiated SV-BR-1-GM ~20x106 cells, intradermally 48-72 hours after cyclophosphamide (300 mg/m2), followed by interferon-alpha at the inoculation sites 2 days later) was administered q3wks with a CPI. Endpoints included PFS, OS and disease control rate (the proportion of patients with stable disease, partial or complete responses) using the KM method censored to the data-cut date prior to data lock. Adverse events were classified according to their severity and relationship to treatment regimen. Results: All pts were heavily pretreated (median 6 prior lines, range 3 - 13). Median age was 62 (41-83). 14 pts had HR+/HER2-, 5 TNBC, and 2 HR+/HER2+ MBC. The remaining pts were HR-/HER2low or HR-/HER2+. Prior ADCs included: 4 ado-trastuzumab emtansine, 14 trastuzumab deruxtecan, 13 sacituzumab govitecan; 8 pts received > 1 ADC. 7 pts had also received ≥ 1 prior CPI line. To date, pts received a median 3 cycles of Bria-IMT™ + CPI (2-7). Kaplan-Meier analysis revealed a median OS of 42 weeks with survival of 69% at 6 months. The subset experienced a median PFS of 74 days with 40% of pts demonstrating a Bria-IMT PFS (PFS2) similar to or > their prior line PFS (PFS1). 39% of pts experienced a PFS2 ≥ their most recent line of ADC PFS. The disease control rate was 40% among evaluable pts. 43% of pts had a reduction in cancer-associated macrophage-like cell (CAML) levels; median reduction was 36% (22-98%) after 1 cycle. There were no toxicity-related treatment discontinuations. 43% (10/23) reported grade 3 or 4 AEs, independent of study drug causality. No interstitial lung disease (ILD) reported. AEs included injection site reaction (39%), fatigue (26%), and nausea/vomiting (43%), mostly mild to moderate. One case of elevated lipase was the most clinically significant grade 4 AE. Conclusion: The retrospective analysis of the Bria-IMT™ regimen in ADC refractory MBC patients suggests a potential treatment option for this patient population. The absence of serious AEs, notably ILD, and no toxicity-related treatment discontinuations, underscores the regimen's favorable safety profile. Future studies are warranted to confirm these results and explore the potential of Bria-IMT™ in broader clinical settings. Citation Format: Chaitali Nangia, Carmen Calfa, Blaise Bayer, Mingjin Chang, William Williams, Giuseppe Del Priore, Charles Wiseman, Saranya Chumsri. Efficacy and safety of SV-BR-1-GM after progression on ADC in metastatic breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT206.

Vaccines for Respiratory Syncytial Virus Prevention in Older Adults.

This review evaluates the efficacy and safety of novel respiratory syncytial virus (RSV) vaccines approved for adults aged 60 years and older. A literature search through February 27, 2024 was conducted using search terms, such as RSV, viral respiratory illness, vaccine, RSVpreF, RSVpreF3, Prefusion F, Abrysvo, and Arexvy. Data from primary literature and vaccine prescribing information were reviewed, encompassing evaluations of clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. The literature review process resulted in 10 articles included within this article's scope, including the results of 2 major phase III trials presented in detail. Two RSV vaccines, Respiratory Syncytial Virus Vaccine (recombinant [adjuvanted]; RSVpreF3-ASO1E, Arexvy) and Respiratory Syncytial Virus Vaccine (recombinant; RSVpreF, Abrysvo), approved for preventing RSV-associated lower respiratory tract disease (LRTD) in adults aged 60 years or older in the United States are discussed. Results from Phase III trials have demonstrated the efficacy of 1 dose of these vaccines in preventing RSV-associated LRTD across 2 RSV seasons. The Advisory Committee on Immunization Practices currently recommends use of these vaccines under shared clinical decision-making for adults aged 60 years or older. Most common adverse effects include injection site reactions (eg, site pain, redness, and swelling). Administration requires a single intramuscular injection of 0.5 mL, reconstituted prior to administration. The RSVpreF3-ASO1E and RSVpreF vaccines effectively prevent RSV-associated LRTD in adults aged 60 years and older.

Safety of Hepatitis B Vaccines (Monovalent or as Part of Combination) in Preterm Infants: A Systematic Review.

Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.

Favorable Virological Outcome, Characteristics of Injection Site Reactions, Decrease in Renal Function Biomarkers in Asian People with HIV Receiving Long-Acting Cabotegravir Plus Rilpivirine.

Long-acting cabotegravir plus rilpivirine has revolutionized the concept of antiretroviral therapy, but as the causes of virological failure and satisfaction can depend on patient background, real-world data are needed. In this single-center study, we reviewed clinical records of people with HIV (PWH) who received injectable cabotegravir plus rilpivirine between June 2022 and January 2023. We assessed virological and safety outcomes, including injection site reactions (ISRs) and changes in serum creatinine and cystatin C. Seventy-four patients were included. There were no virological failures. Approximately 80% of individuals achieved HIV-RNA undetectable in all visits up to 14 months (median 13 months) after switching. Pain upon injection was significantly more common at the rilpivirine injection site, while delayed pain was significantly more common at the cabotegravir injection site. The serum creatinine (mean difference -0.12 mg/dL, p < .0001) and the cystatin C (mean difference -0.077 mg/dL, p < .0001) decreased significantly after switching, and in multivariable regression analysis, baseline characteristics did not affect the decrease in these renal function markers. Long-acting cabotegravir plus rilpivirine showed excellent antiviral efficacy and safety in PWH in Japan. ISRs were characterized differently at the cabotegravir and rilpivirine injection sites. Although cystatin C showed decrease after the regimen switch, further confirmation is needed whether cabotegravir plus rilpivirine can improve renal function.

Phase 1 Trial of Dendritic Cell/AML Fusion Cell Vaccine after Allogeneic Stem Cell Transplant in Acute Myeloid Leukemia

Introduction We have developed a vaccine in which patient-derived AML cells are fused with donor-derived dendritic cells (DCs). Vaccination after initial remission and consolidation was shown to elicit leukemia-specific immune responses. We hypothesized that donor-derived DC/AML vaccination post-transplant would elicit the durable expansion of leukemia-specific T cells within the donor T cell repertoire to effectively protect against disease relapse. We report updated results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine following allogeneic transplant. Methods DC/AML fusion vaccine was generated with patient leukemia blasts, cryopreserved at the time of diagnosis, and donor-derived DCs, from leukapheresis of patients who achieved hematopoietic recovery and remained in CR 25-90 days after an allogeneic transplant. DCs were differentiated via culture of adherent mononuclear cells in the presence of GM-CSF, IL-4 and TNFa. Vaccine was administered starting day 70-100 post-transplant as long as the patient did not have active GVHD requiring therapy. Two doses of the vaccine were given subcutaneously at 3 week intervals, in conjunction with 100 mcg GMCSF daily at the vaccine site for 4 days. A booster vaccine was given 30-60 days following the taper of immune suppression, in the absence of GVHD. Longitudinal profiling of the immune landscape by single cell RNA sequencing and CyTOF from peripheral blood samples obtained before and after vaccination is underway. Immunologic response of leukemia-specfic T cells is being evaluated via IFN-gamma expression following stimulation with autologous tumor lysate. OS was calculated using Kaplan Meier Curve. Results 27 participants have been enrolled with median age 59 years (range 23-74). 15 patients were transplanted with a matched unrelated donor, 10 with a matched sibling donor and two with a haplo-identical donor. One patient relapsed prior to leukapheresis and was ineligible. The median yield of leukemia cells was 218x10 6 (range 62-818x10 6)and mean viability was 97%. The median yield of DCs was 106x10 6 (range 19-182x10 6) and mean viability 81%. Fusion vaccine was successfully generated in 25 of 26 patients who underwent leukapheresis; one patient had insufficient DC. Mean fusion efficiency was 47% with viability of 79%. Mean fusion vaccine dose was 3.8 x10 6 cells. 6 patients from whom vaccine was generated did not meet eligibility to initiate vaccination due to GVHD or COVID19 infection. 19 participants initiated vaccine administration and are evaluable for toxicity and immunologic response. The most common side effects were vaccine site reactions (n=10 grade 1, n=2 grade 2). 5 patients developed GVHD that was attributed as possibly related to vaccination, at a median time of 17 days after vaccination (range 5-70 days). Acute GVHD included two events of skin grade 2, one GI grade 2, one liver and skin grade 3. Chronic GVHD included a moderate event affecting 3 organs and severe event affecting 4 organs. There were 10 additional GVHD events with a median time of 108 days post vaccination (range 7-126 days), assessed as unlikely related or unrelated to vaccine based on pre-existing GVHD and timing of onset. Median time of follow-up is 23 months post-transplant (range 11-59 months). Amongst 19 vaccinated patients, 14 remained in CR and median overall survival estimate is 49 months post transplant. 3 died of relapsed disease, 2 died of GVHD and/or infection, and 1 died of unknown cause. Preliminary results of PB CyTOF from 4 patients in remission and 1 patient that relapsed indicate higher proportions of T cells and DCs in patients in CR. Interferon expression was higher in a patient with durable remission while absent from a patient with early relapse. Conclusions Vaccination using host-derived leukemia cells and donor derived DC was safe and feasible. Adverse events post vaccination have included injection site reactions as well as acute and chronic graft versus host disease. Vaccination may be a promising strategy to reduce relapse as 14 of 19 vaccinated patients remain relapse free. Albeit this approach is limited to patients who have not had early relapse or early GVHD. Immunologic response by interferon release upon lysate stimulation, CyTOF and single cell RNA sequencing of the immune milieu will be reported.

Safety of COVID-19 mRNA vaccination and effects of SARS-CoV-2 infection in children and adults with mast cell disorders.

Mastocytosis is characterized by abnormal clonal mast cell proliferation. Given the paucity of data in patients with mastocytosis, it is crucial to assess the safety of COVID-19 vaccines in this population. We aimed to assess the risk of allergic reactions and the effect of COVID-19 infection among patients with mastocytosis. Participants were recruited from Canada and Israel between December 2021 and May 2022. Consenting participants were administered standardized questionnaires querying whether they were infected with COVID-19, if they received the first and second dose vaccines, and post-vaccination side effects including allergic reactions (urticaria/angioedema, current rash flaring, need for updosing medications, or respiratory symptoms) and common side effects including injection site reaction (ISR) and flu-like symptoms. Forty participants with mastocytosis were administered a standardized questionnaire (median age = 9, 59% male). Amongst all participants, 16 (39%) reported COVID-19 infection and most (75%) reported flu-like symptoms, 3 (19%) were asymptomatic, 1 suffered from shortness of breath/chest pain and 1 from facial flushing. Of the 25 participants who were eligible for vaccination (≥ 5years old), 80% received a first-dose vaccine and 68% received a second-dose vaccine. Of those who received the first-dose vaccine, most (60%) remained asymptomatic, 20% developed flu-like symptoms, 20% had an ISR, and 1 patient had an allergic reaction (urticaria and swelling). Of those who received the second-dose vaccine, most (53%) were asymptomatic, and 1 had an allergic reaction. No significant difference was found between side effects of both vaccine doses. No reactions fulfilled the criteria for anaphylaxis in either dose. This study reveals that among patients with mastocytosis, COVID-19 vaccine and infection were well-tolerated in the majority of cases.

Ulcerative colitis and pyoderma gangrenosum presentation of a case and brief literature review

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder comprised of Crohn's disease and ulcerative colitis. Ulcerative colitis affects the large intestine, while Crohn's disease can affect any part of the gastrointestinal tract (GIT). IBD is a multisystem condition that predominantly affects the gastrointestinal, musculoskeletal, ocular, and cutaneous systems. The following dermatological manifestations associated with IBDs have been identified: Specific manifestations with the same histological features of the underlying only ocurrs in Crohn Disease (CD); cutaneous disorders associated with IBD aphthous stomatitis, erythema nodosum; reactive mucocutaneous manifestations of IBDs pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis y mucocutaneous conditions secondary to treatment including injection site reactions y eczema and manifestations due to nutritional malabsorption such as stomatitis, glossitis, angular cheilitis hair and nail abnormalities. We believe dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance, such as psoriasiform eruption. One of the cutaneous manifestations associated with UC is pyoderma gangrenosum (PG), which is an inflammatory neutrophilic dermatosis that clinically presents with well-defined ulcers with an erythematous border and mucopurulent or hemorrhagic exudate.We present the case of a 44-year-old female patient, who presented non-specific chronic ulcerative colitis (UC) with active intestinal symptoms, fever, diarrhea and hematochezia, 20 days later it began with pustules on the head, trunk and extremities, which evolved into an ulcer with a border erythematous and well defined whose clinical and histopathological diagnosis corresponded to pyoderma gangrenosum.

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

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. 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. 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. 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.

A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2–positive breast cancer.

532 Background: Patients (pts) with early stage HER2-positive breast cancer are commonly treated with neoadjuvant HER2-targeted therapy. Pts who have residual invasive disease have a less favorable outcome and increased risk of recurrent disease than pts with a complete pathologic response (pCR). It also has been observed that pts who do not achieve a pCR have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting anti-HER-2 CD4 Th1 response using vaccines will be safe, induce anti-tumor immunity in HER2-positive breast cancer and reduce the risk of recurrence. We conducted a multi-center, phase 2, randomized study to determine the safety, immunogenicity and recurrence free survival of two HER2 vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: Pts with HER2-positive early breast cancer were eligible if they had residual invasive disease at surgery after receiving neoadjuvant chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio, with stratification according to residual cancer burden (RCB) (1+2 vs 3) to receive adjuvant HER2 vaccination with either DC1 or WOKVAC. For the initial vaccination phase, DC1 was delivered via US guided inguinal lymph node administration, weekly x 6 weeks and WOKVAC was given intradermally on weeks 1, 4, and 7. Booster vaccines were given at months 6, 9 and 12. The primary end point is to evaluate the safety and tolerability of each vaccine and assess immune response rate as measured by ELISPOT. Each treatment arm will be assessed separately. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune correlative biomarkers. Here we are reporting the initial safety results. Results: Total of 110 eligible pts (55 WOKVAC vs 55 DC1) were enrolled from 2/2018 to 12/2022 and received at least one dose of treatment and 38 pts pending completion of the booster phase. Most pts had clinical stage II/III 56/35 (82%) and 50% had positive node disease at diagnosis. 82% had hormone receptor positive disease. 37/38/8 patients had RCB 1/2/3. For patients without known RCB status, ypTNM was used to randomize (yp stage I/II/III = 13/13/1 pts). The most frequently observed treatment related adverse events (TRAE) were injection site pain/reaction (38%) and chills (34%), fever (25%) and fatigue (40%) for DC1 arm. For WOKVAC, the most common toxicities included injection site reaction (68%) and fatigue (37%). All of these were grade 1 and 2. Nine patients had events including new primary cancer (1), local recurrence (2), metastatic disease recurrence (6). Conclusions: Both DC1 and WOKVAC HER2 vaccines were well tolerated without significant toxicities. Updated results will be presented at the meeting including correlatives. Clinical trial information: NCT03384914 .

P149 An Exploratory Trial Assessing Finger Perfusion, Raynaud’s Condition Score and Safety, Following a Single Dose of CAM2043 (Treprostinil Subcutaneous Depot) in Patients with Raynaud's Phenomenon Secondary to Systemic Sclerosis

Abstract Background/Aims Prostacyclin analogues, although effective treatment for systemic sclerosis (SSc)-related Raynaud’s phenomenon (RP), have the disadvantage of requiring intravenous or subcutaneous (SC) infusion. Treprostinil subcutaneous depot (CAM2043) is a novel extended-release SC formulation of treprostinil. The aim of this trial was to explore the effect of a single SC dose of CAM2043 on skin temperature (indirect measure of perfusion), as evaluated by thermography following cold challenge. Methods This was an exploratory, open-label, single-dose Phase 2 trial. Ten female patients (mean age 54.9 years) with mean SSc duration of 11.5 years (all anticentromere antibody positive) and mean RP duration of 14.5 years, were recruited. To be included, patients had to experience ≥5 attacks of RP/week. Patients attended on 6 occasions: screening, baseline (Day 1), and on Days 2, 3, 8, and 15. At baseline, each patient received a single SC injection of 2.5 mg CAM2043 (except the first patient who received 5mg CAM2043). A standard cold challenge test of the hands (15 °C for one minute) was performed pre-dose and at 3-, 6-, 24-, 72-, 168- and 336-hours post-dose, with temperature responses over the subsequent 15 minutes measured by infrared thermography. The primary endpoint was the mean change from baseline to 6 hours post-dose in the area under the curve (AUCtherm) for rewarming (8 fingers). Secondary endpoints included: change from baseline in AUCtherm, maximum temperature after rewarming (MAX) and Raynaud’s Condition Score (RCS). Safety and tolerability were assessed throughout the trial. Results AUCtherm increased 6 hours post-dose, but not statistically significantly: mean increase 192.7 °C×sec (95% CI: -727.1, 1112.6). AUCtherm was significantly greater at 24 hours than at baseline (mean increase 1175.8 °C×sec (95% CI: 127.3, 2224.3)), with a trend towards mean AUCtherm values higher than baseline up to 168 hours post-dose (Day 8) and returning to baseline values at 336 hours (Day 15). A statistically significant increase from baseline was also seen for MAX at 24 hours: mean increase 1.4 °C (95% CI: 0.1, 2.7). At baseline, mean (SD) RCS was 3.7 (1.3) units (10-point scale), and was significantly improved post dosing, including Day 8 (mean reduction 1.6 units (95% CI: -2.68, -0.52)). This positive treatment effect persisted at Day 15 (mean reduction 1.6 units (95% CI: -3.33, 0.19)). Adverse events were reported by all 10 patents: all reported erythema and pain at the injection site. Conclusion Finger skin temperature rose after CAM2043 treatment (significantly at 24 hours post-dose), with significant improvements in RP symptoms (RCS) over the 15-day period following dosing indicating a positive treatment effect. Overall, the safety profile for CAM2043 was consistent with known safety profile for treprostinil, including injection site reactions. The results indicate that CAM2043 could be further investigated in clinical trials of RP. Disclosure A.L. Herrick: Consultancies; Camurus AB. A. Murray: None. G. Dinsdale: None. J. Manning: None. C. Chukwu: None. M. Alvarez Fernandez: Corporate appointments; Camurus AB (employee). J.R. Seibold: Corporate appointments; Medical Lead, Prometheus Biosciences. Consultancies; Camurus AB, Alexion, GlaxoSmithKline, Mitenyi. Shareholder/stock ownership; Prometheus Biosciences. Other; Advisory Committee/Boards: CSL Behring, Prometheus Biosciences, Mitenyi. F. Tiberg: Corporate appointments; President &amp; CEO Camurus AB. Shareholder/stock ownership; Camurus AB. Other; Board Member Camurus AB and Amniotics AB.

Safety of measles, mumps, and rubella vaccine in adolescents and adults in the vaccine safety Datalink

Measles, mumps, and rubella vaccine (MMR) is routinely administered to children; however, adolescents and adults may receive MMR for various reasons. Safety studies in adolescents and adults are limited. We report on safety of MMR in this age group in the Vaccine Safety Datalink. We included adolescents (aged 9-17years) and adults (aged≥18years) who received≥1 dose of MMR from January 1, 2010-December 31, 2018. Pre-specified outcomes were identified by diagnosis codes. Clinically serious outcomes included anaphylaxis, encephalitis/myelitis, Guillain-Barré syndrome, immune thrombocytopenia, meningitis, and seizure. Non-serious outcomes were allergic reaction, arthropathy, fever, injection site reaction, lymphadenopathy, non-specific reaction, parotitis, rash, and syncope. All serious outcomes underwent medical record review. Outcome-specific incidence was calculated in pre-defined post-vaccination windows. A self-controlled risk interval design was used to determine the relative risk of each outcome in a risk window after vaccination compared to a more distal control window. During the study period, 276,327 MMR doses were administered to adolescents and adults. Mean age of vaccinees was 34.8years; 65.8% were female; 53.2% of doses were administered simultaneously with≥1 other vaccine. Serious outcomes were rare, with incidence≤6 per 100,000 doses for each outcome assessed, and none had a significant elevation in incidence during the risk window compared to the control window. Incidence of non-serious outcomes per 100,000 doses ranged from 3.4 for parotitis to 263.0 for arthropathy. Other common outcomes included injection site reaction and rash (157.0 and 112.9 per 100,000 doses, respectively). Significantly more outcomes were observed during the risk window compared to the control window for all non-serious outcomes except parotitis. Some variability was observed by sex and age group. Serious outcomes after MMR are rare in adolescents and adults, but vaccinees should be counseled regarding anticipated local and systemic non-serious adverse events.

Clinical Efficacy of Biosimilar Switch of Adalimumab for Management of Uveitis

ABSTRACT Background Adalimumab has demonstrated efficacy in non-infectious uveitis. With the introduction of biosimilar agents such as Amgevita, we aimed to quantify efficacy and tolerability compared to Humira in a multi-centre UK cohort Methods Patients identified from tertiary uveitis clinics in 3 centres, after institution-mandated switching was implemented. Results Data collected for 102 patients, aged 2–75 years, with 185 active eyes. Following switch, rates of uveitis flare were not significantly different (13 events before, 21 after, p = .132). Rates of elevated intraocular pressure were decreased (32 before, 25 afterwards, p = .006) and dosing of oral and intra-ocular steroids was stable. Twenty-four patients (24%) requested to return to Humira, commonly due to pain from injection or technical difficulty with the device. Conclusion Amgevita is safe and effective for inflammatory uveitis with non-inferiority to Humira. Significant numbers of patients requested to switch back due to side effects including injection site reactions.

Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews.

This paper aimed to comprehensively evaluate the effectiveness and safety of Inclisiran in treating hyperlipidemia through an overview of systematic reviews (SRs). The Cochrane Library, EMBASE, PubMed, CNKI, WANGFANG database, VIP database, ClinicalTrials.gov, and ICRT were searched electronically to collect SRs and meta-analysis of Inclisiran in hyperlipidemia treatment from the establishment of the database till May 2022. Two researchers independently screened the relevant literature, then the assessment of multiple systematic reviews tool was made into assess the methodological quality of the included studies. Data extracted were used to perform the study through RevMan5.3 software. The grading of recommendations assessment, development, and evaluation tool was used to grade the quality of the evidence of the outcomes included in the SRs. Prospero ID: CRD 42022326845. A total of 10 relevant SRs were included, involving 7 randomized controlled trials. The assessment results of the assessment of multiple systematic reviews tool suggested that the quality of the SRs included needed to be improved. The reduced level of low-density lipoprotein cholesterol of the experimental group was lower than the control group, and the difference in the amount of effectiveness was statistically significant (MD = -50.13, 95%CI: -56.2 to -44.06, P < .00001). The grading of recommendations assessment, development, and evaluation results showed that out of 27 outcomes, 8 were high-quality, 3 were of medium quality, 6 were of low quality, and 10 were of the most inferior quality. 300mg Inclisiran with 2 injections a year has the best therapeutic effect, which can significantly reduce low-density lipoprotein cholesterol and total cholesterol, and increase high-density lipoprotein cholesterol levels in patients with hyperlipidemia. Inclisiran has a favorable safety profile, with no significant difference in the incidence of adverse reactions compared to a placebo. Most of the adverse effects were associated with the reaction on the injection site.

Injections Site Reactions and Biologics for Psoriasis: A Questionnaire Based Real Life Study.

Biologic selection for psoriasis treatment should take into account numerous factors including injection site reactions (ISRs) such as swelling at the injection site, pain, burning, erythema, all possibly reducing patient adherence. A 6-months observational real life study was performed involving psoriasis patients. Inclusion criteria were age ≥ 18 years, moderate-to-severe psoriasis diagnosis since at least 1 year, patients being on biologic treatment for psoriasis ≥ 6 months. A 14-item questionnaire was administered to all patients enrolled to assess whether the patient ever experienced ISRs after the injection of the biologic drug. 234 patients were included: 32.5% received an anti-TNF-alpha drug, 9.4% received anti-IL12/23, 32.5% received an anti-IL17, 25.6% received an anti-IL23. 51.2% of study population reported at least one symptom related to ISR. 35.9% of patients experienced pain, 31.6% swelling, 28.2% burning sensation and 17.9% erythema. 3.4% of the surveyed population experienced anxiety or fear of the biologic injection due to ISRs symptoms. The greater incidence of pain was registered in anti-TNF-alpha and anti-IL17 groups (47.4% and 42.1%, p<0.01). Ixekizumab proved to be the drug with the highest rate of patients experiencing pain (72.2%), burning (77.7%) and swelling (83.3%). No patients reported biologics discontinuation or delay for ISRs symptoms. Our study highlighted that each different class of biologics for psoriasis was linked to ISRs. These events are more frequently reported with anti-TNF-alpha and anti-IL17.

Vaccinating Children against SARS-CoV-2: A Literature Review and Survey of International Experts to Assess Safety, Efficacy and Perceptions of Vaccine Use in Children.

Introduction: The balance of risks and benefits of COVID-19 vaccination in children is more complex than in adults with limited paediatric data resulting in no global consensus on whether all healthy children should be vaccinated. We sought to assess the safety, efficacy, and effectiveness of childhood vaccination against SARS-CoV-2, as well as better understanding perceptions of vaccination in parents and vaccine experts. Methods: We performed a literature review for COVID-19 vaccine safety, efficacy, effectiveness, and perceptions. We searched international safety databases for safety data and developed an electronic survey to elicit country-specific COVID-19 immunisation data, including vaccine regulations, policies, rates, and public attitudes solicited from vaccine experts. Results: Nine studies were included in the final safety analysis. Local reactions were frequently reported across all studies and vaccine types. Adverse events reported to surveillance systems tended to be non-serious, and commonly included injection site reactions and dizziness. Twenty-three studies reported immunogenicity, efficacy, and effectiveness data. There were nine randomised control trials of six different vaccine types, which showed seroconversion of neutralising antibodies in vaccinated children ranging from 88% to 100%. The vaccine efficacy for Pfizer and Moderna vaccines ranged from 88% to 100%. There were 118 survey responses representing 55 different countries. Reported vaccination rates ranged from <1% to 98%. Most respondents described “mixed opinions” regarding paediatric vaccination policies in their country. By region, a more positive public attitude towards vaccination correlated with higher vaccination rates. Discussion: In this mixed-methods review, we have found evidence that vaccination against COVID-19 in children is safe, efficacious, and effective. Overall, the combined evidence from both the literature review and survey highlights the need for further data on both the safety and effectiveness of COVID-19 vaccinations in children.

Safety Monitoring of JYNNEOS Vaccine During the 2022 Mpox Outbreak — United States, May 22–October 21, 2022

JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.

Patient and Health Care Professional Perspectives on Quality of Life and Unmet Needs of People with Chronic Neutropenia: A Survey-Based Assessment

Introduction Chronic neutropenia (CN) encompasses different blood disorders all characterized by low levels of neutrophils (absolute neutrophil count [ANC] <1500/µL for >3 months), that substantially alters quality of life (QoL) of affected individuals due to disease-related symptoms [James RM. Arch Dis Child. 2006; Donadieu J. Exp RevHematol. 2021]. Granulocyte colony-stimulating factor (G-CSF) treatment can improve clinical outcomes, but chronic use is associated with debilitating side effects, such as bone pain, that have negative impact on QoL [Michniacki TF. Blood. 2019; Dale DC. N Engl J Med. 2017; Mehta HM. J Immunol. 2015; Donadieu J. Orphanet J Rare Dis. 2011]. This survey evaluated views of patients/caregivers (P/Cs), and health care professionals (HCPs) on unmet needs, treatment patterns, impact on daily life, and QoL of people living with CN. Methods Participants were recruited via direct emails to patients with CN and outreach to CN Facebook groups from Savvy Cooperative and X4 Pharmaceuticals. P/Cs (n=22) completed up to 29 survey questions; 13 screening questions captured demographics, neutropenia type, and treatment setting. Patients with chemotherapy-induced neutropenia were ineligible. Additional 16 questions captured information on severity, symptoms, impact on daily life, treatment types, and unmet needs. HCPs (n=7) completed a 13-question survey; 7 screening questions captured data on medical specialty and experience treating neutropenia, and 6 questions captured patient neutropenia type, treatment patterns, and unmet needs. Preliminary results per responses through July 8, 2022, are presented; additional updates are pending upon survey close. Results Patients (n=18)/caregivers (n=4) completed a validated survey. Included patients were aged 2 to 65 years (45%, 45-65 years). Neutropenia types were idiopathic (32%), congenital (23%), cyclic (18%), autoimmune (14%), and unsure (14%). Most HCPs (86%) served at large academic institutions, with 57% practicing for >21 years. Medical specialties included pediatric hematology/oncology (57%) and adult/pediatric immunology (57%). Medications prescribed included G-CSF (71%), immunoglobulin (Ig) replacement (43%), and antibiotics (14%). G-CSF (29%) and Ig (29%) had the most difficult-to-manage side effects. When asked which symptoms most impacted health of a person with CN, P/Cs listed fatigue (77%) and frequent/severe infections (77%) as top symptoms, while HCPs listed mouth sores (71%), dental issues (57%), and frequent/recurrent infections (57%). P/Cs reported long-term neutropenia (90%), emotional stress (68%), and disruption to family/social life and social isolation (64%) as top 3 daily life concerns. When asked what treatment improvements are needed, P/Cs listed administration of medication (64%) and reducing fatigue (36%) at the top; HCPs listed fewer/less frequent severe infections (57%) and administration of medication (57%). Improvements in "administration of medication” included alleviation of the burdens associated with injection/intravenous treatments including injection site reactions. P/Cs reported G-CSF as the most prescribed treatment (64%). Top issues with G-CSF treatment were bone pain (71%) and fatigue (50%); 50% reported G-CSF dose/frequency adjustments; 45% were due to side effects such as bone pain. Six of 7 HCPs (86%) reported adjusting G-CSF dose/frequency, and 1 (17%) attributed the change to side effects. Conclusions Interim survey results show differing perspectives between P/C and HCPs on impact of CN and its treatment on QoL. P/Cs cited fatigue as most impactful symptom and fatigue reduction as a priority treatment need, while HCPs ranked fatigue at the bottom or not at all. Notably, the relationship between fatigue and CN is poorly understood and requires further study. Although both groups reported improvement in medication administration as a need, perceptions of patient experience with current treatment differ. P/Cs more commonly cited side effects as the cause of medication changes. Survey results show considerable impact of CN on the lives of people diagnosed and suggest the existing treatment paradigm is burdensome and insufficiently addresses physical health/QoL needs. Additional studies are required to understand unmet needs of people with CN and reasons behind differing perspectives between P/C and HCP communities.