Comparing Injection Site Reactions of Aprepitant and Fosaprepitant in Gynecologic Cancer Chemotherapy.

BACKGROUND/AIM: The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). PATIENTS AND METHODS: This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. RESULTS: The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. CONCLUSION: Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

Cabotegravir + Rilpivirine Long-Acting: Overview of Injection Guidance, Injection Site Reactions, and Best Practices for Intramuscular Injection Administration.

Background: Cabotegravir (CAB) + rilpivirine (RPV) dosed monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of human immunodeficiency virus type 1 virologic suppression. Across the phase 3/3b trials, the most frequently reported adverse events were injection site reactions (ISRs). Methods: We present pooled ISR characteristics and outcomes for participants receiving CAB + RPV LA through week 96 of the FLAIR and ATLAS-2M studies, and survey results from healthcare providers (HCPs) giving injections (eg, injectors) in the ATLAS, FLAIR, and ATLAS-2M studies to determine optimal injection techniques. Surveys were anonymous, self-administered online questionnaires that queried provider demographics, injection experience, and techniques to minimize pre-/postinjection discomfort. Data were summarized using descriptive statistics. Results: Overall, 8453 ISRs were reported by 801 participants receiving ≥1 injection of CAB LA/RPV LA. Most ISRs were mild to moderate in severity (grade 1-2, 99%), with a median duration of 3 days (interquartile range, 2-4 days), and rarely led to withdrawal (2%). Surveys were completed by 181 HCPs across 113 sites. Pushing the intramuscular injection at slow speed (66%), bringing the medication to room temperature (58%), and relaxing the gluteus muscle before injecting (53%) were ranked as effective preinjection/injection procedure practices for minimizing pain. Most injectors (60%) indicated that a prone position provided optimal patient comfort, and 41% had no preference on injection medication order. Conclusions: Taken together, the data demonstrate favorable tolerability with CAB + RPV LA injections over the long term and simple techniques routinely used by injectors to help optimize the administration of CAB + RPV LA injections.

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.

Comparison of the Effect of Intracarpal Injection of Ketorolac With Triamcinolone in Carpal Tunnel Syndrome: A Randomized Controlled Trial.

BACKGROUND: The most prevalent entrapment neuropathy is carpal tunnel syndrome (CTS). Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently prescribed for musculoskeletal disorders, oral NSAIDs do not provide any additional benefits for CTS. Nevertheless, the use of NSAID phonophoresis has shown significant improvement, possibly due to increased concentration in the target tissue. The effects of intracarpal injection of NSAIDs on CTS have not been studied. OBJECTIVE: We conducted a controlled trial to compare the efficacy of ketorolac and triamcinolone in treating CTS. METHODS: Mild to moderate CTS patients were randomly assigned to receive either a local injection of 30 mg ketorolac or 40 mg triamcinolone. Patients were evaluated using visual analog scale (VAS) for pain, severity, function, electrodiagnostic findings, patient satisfaction, and any complications at the injection site, at baseline and 12 weeks after the procedures. RESULTS: Fifty patients participated, and 43 completed the study. Both groups showed significant improvement in the VAS, severity, function, and electrodiagnostic scores at 3 months compared with the baseline. A comparison of the groups showed significant differences in VAS, severity, and function, with the improvement being significantly higher in the triamcinolone group. CONCLUSION AND RELEVANCE: The present study showed that injection of triamcinolone or ketorolac into the carpal tunnel relieved pain, increased function, and improved electrodiagnostic findings in patients with mild to moderate CTS. It also showed that triamcinolone was superior to ketorolac in terms of analgesic effect and resulted in greater improvement in symptom severity and function.

Eventos adversos pós-vacina contra o papilomavírus humano em adolescentes: revisão sistemática da literatura / Adverse events following human papillomavirus vaccine in adolescents: systematic review of the literature / Eventos adversos tras la vacuna contra el virus del papiloma humano en adolescentes: revisión sistemática de la literatura

Objetivo: O objetivo desse estudo foi investigar a ocorrência de Eventos Supostamente Atribuídos a Vacinação e/ou Imunização associados à vacina Papilomavírus Humano entre adolescentes de ambos os sexos. Métodos:Trata-se de uma revisão sistemática, realizada segundo os preceitos do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Resultados: Inicialmente, foram identificados 11.016 artigos e, após a remoção de duplicidades, restaram 6.824. Destes, 59 foram selecionados para leitura na íntegra. Ao final, nove estudos compuseram a amostra. Os resultados indicam que a maioria dos Eventos Supostamente Atribuídos a Vacinação e/ou Imunização foram leves e moderados, prevalecendo eventos no local da injeção, como a dor e edema. Os Eventos Supostamente Atribuídos a Vacinação e/ou Imunização sistêmicos mais frequentes foram a febre, cefaleia, fadiga e tontura. Conclusão: A vacina contra o Papilomavírus Humano para os adolescentes é segura, reforçando-se sua importância como estratégia para diminuir as taxas de incidência dos cânceres associados ao Papilomavírus Humano.

Objective: The objective of this study was to investigate the occurrence of Events Supposedly Attributable to Vaccination and/or Immunization associated with the Human Papillomavirus vaccine among adolescents of both sexes. Methods: This is a systematic review carried out according to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Initially, 11,016 articles were identified, of which 6,824 remained after removing duplicates, and 59 of these were selected for full reading. The sample comprised nine studies. The results indicate that most Events Supposedly Attributable to Vaccination and/or Immunization were mild and moderate, and events at the injection site, such as pain and edema, prevailed. The most common systemic Events Supposedly Attributable to Vaccination and/or Immunization were fever, headache, fatigue and dizziness. Conclusion: The Human Papillomavirus vaccine for adolescents is safe, reinforcing its importance as a strategy to reduce the incidence rates of Human Papillomavirus associated cancers

Objetivo: El objetivo de este estudio fue investigar la ocurrencia de Eventos Supuestamente Atribuibles a la Vacunación o Inmunización asociados a la Vacuna contra el Virus del Papiloma Humano entre adolescentes de ambos sexos. Métodos: Se trata de una revisión sistemática realizada según la declaración Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Resultados:Se identificaron 11.016 artículos y, tras eliminar duplicados, quedaron 6.824. De ellos, 59 fueron seleccionados para lectura completa. La muestra estuvo compuesta por nueve estudios. Los resultados indican que la mayoría de los Eventos Supuestamente Atribuibles a la Vacunación o Inmunización fueron leves y moderados, prevaleciendo los eventos en el lugar de la inyección, como dolor y edema. Los Eventos Supuestamente Atribuibles a la Vacunación o Inmunización sistémicos más comunes fueron fiebre, dolor de cabeza, fatiga y mareos. Conclusión: La vacuna contra el Virus del Papiloma Humano para adolescentes es segura, lo que refuerza su importancia como estrategia para reducir las tasas de incidencia de cánceres asociados al Virus del Papiloma Humano.

Pilomatricoma Growing at the SARS-CoV-2 mRNA Vaccination Site.

A healthy 21-year-old woman was presented to our outpatient clinic with an asymptomatic swelling on her left arm. She reported the administration of two doses of BNT162b2 mRNA vaccination at the lesion site earlier. The pathology report confirmed the diagnosis of pilomatricoma. Previously, needlestick trauma and various immunisations have been attributed to the development of pilomatricoma. We present this case to emphasise the possible association between BNT162b2 mRNA vaccination and pilomatricoma development. The role of persistent inflammation is also discussed.

Laser treatment for adverse reactions to injectable facial filling: a systematic review.

Facial filling is widespread in society, albeit associated with inherent risks. This review analyzes clinical studies using laser therapy for filler complications to assess its safety and efficacy as an alternative treatment. A literature search was conducted up until April 2023, encompassing five different databases: PubMed, Scopus, Embase, Web of Science, and Medline, to find clinical trials addressing patients who underwent laser treatment for adverse reactions to injectable facial filling. The outcome variables were the clinical assessment of the lesion and the occurrence of post-intervention complications/sequelae. The risk of bias was assessed using the ROBINS-I tool. In total, six studies were included, all classified as having a "moderate risk" of bias. A total of 533 patients underwent laser treatment for adverse reactions to injectable facial fillers. The diode laser was the most frequently utilized equipment, with positive results reported in five studies. Among all treated patients, 96.24% achieved partial or complete resolution, 0.22% experienced some sequelae or complications, and only 0.01% showed no improvement. Laser treatment can eliminate the necessity for surgical intervention for adverse reactions to injectable facial fillers, resulting in partial or complete improvement of the condition.

Painful and recurring injection site reaction to alirocumab and evolocumab in a young woman with familial hypercholesterolemia and effective therapeutic alternative based on inclisiran: a case report.

A 28-year-old woman with autosomal dominant familial hypercholesterolemia (FH) with a probable coexistent polygenic contribution causing very high low-density lipoprotein-cholesterol (LDL-C) levels, started therapy with the proprotein convertase subtilisin/kexin type 9-inhibitor (PCSK9i) alirocumab, in addition to high-intensity statin plus ezetimibe. Forty-eight hours after the second injection of alirocumab, the patient developed a painful palpable injection site reaction (ISR) that recurred after the third administration of the drug. Treatment was then switched to evolocumab, another PCSK9i, but the patient had an ISR with similar features. The most conceivable cause of the ISR was a cell-mediated hypersensitivity reaction to polysorbate, an excipient contained in both drugs. Although ISR after PCSK9i administration is usually transient and does not compromise the continuation of treatment, in this case the recurrence of such side effect in an exacerbated way led to treatment withdrawal, with a subsequent re-exposure to increased cardiovascular (CV) risk. As soon as it became available in clinical practice, the patient started treatment with inclisiran, a small interfering RNA targeting hepatic PCSK9 synthesis. No adverse events were reported after inclisiran administration and LDL-C levels decreased significantly, confirming the evidence that this innovative approach to hypercholesterolemia is a safe and effective resource in patients at high CV risk who cannot achieve LDL-C goal with conventional lipid-lowering therapies and antibody-based PCSK9i.

Cannabidiol (CBD) for the treatment of subcutaneous treprostinil (Remodulin®) site pain: a case report.

Background: Pulmonary arterial hypertension occurs as a result of vascular remodeling and dysregulation of endothelial cells that narrows small pulmonary arteries and raises precapillary pressures. Pulmonary arterial hypertension is a rare and progressive disease characterized by dyspnea, chest pain, and syncope. Parenteral treprostinil is indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise. Up to 92% of patients treated with treprostinil via subcutaneous delivery experienced infusion site pain and approximately 23% discontinued treatment due to site pain. Cannabidiol salve may have analgesic and anti-inflammatory properties and could be an additional option for patients with infusion site pain. Case report: Two patients with pulmonary arterial hypertension were treated with cannabidiol salve. Both patients reported a reduction in infusion site pain without the need for narcotics. Conclusion: These two cases suggest that cannabidiol salve may help to minimize redness and alleviate pain at the infusion site. Additional studies are required to test the effectiveness of cannabidiol in a larger group of patients with infusion site pain.

Unique structure of ozoralizumab, a trivalent anti-TNFα NANOBODY® compound, offers the potential advantage of mitigating the risk of immune complex-induced inflammation.

Biologics have become an important component of treatment strategies for a variety of diseases, but the immunogenicity of large immune complexes (ICs) and aggregates of biologics may increase risk of adverse events is a concern for biologics and it remains unclear whether large ICs consisting of intrinsic antigen and therapeutic antibodies are actually involved in acute local inflammation such as injection site reaction (ISR). Ozoralizumab is a trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. Treatment with ozoralizumab has been shown to provide beneficial effects in the treatment of rheumatoid arthritis (RA) comparable to those obtained with other TNFα inhibitors. Very few ISRs (2%) have been reported after ozoralizumab administration, and the drug has been shown to have acceptable safety and tolerability. In this study, in order to elucidate the mechanism underlying the reduced incidence of ISRs associated with ozoralizumab administration, we investigated the stoichiometry of two TNFα inhibitors (ozoralizumab and adalimumab, an anti-TNFα IgG) ICs and the induction by these drugs of Fcγ receptor (FcγR)-mediated immune responses on neutrophils. Ozoralizumab-TNFα ICs are smaller than adalimumab-TNFα ICs and lack an Fc portion, thus mitigating FcγR-mediated immune responses on neutrophils. We also developed a model of anti-TNFα antibody-TNFα IC-induced subcutaneous inflammation and found that ozoralizumab-TNFα ICs do not induce any significant inflammation at injection sites. The results of our studies suggest that ozoralizumab is a promising candidate for the treatment of RA that entails a lower risk of the IC-mediated immune cell activation that leads to unwanted immune responses.

Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use.

Dupilumab is a humanized monoclonal antibody approved for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, atopic dermatitis, eosinophilic esophagitis, and prurigo nodularis. The most common adverse reactions from dupilumab use are temporary injection site reactions and ocular surface reactions; however, a variety of both acute and delayed cutaneous reactions have also been described. We present a case of delayed hyperpigmented injection site reactions following chronic dupilumab use.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

The pharmacist's role in reducing infusion-related phlebitis.

PURPOSE: Pharmacists oversee parenteral drug preparation and administration in hospitals, clinics, infusion centers, and home infusion settings. Infusion-related phlebitis (IRP), the most common complication of intravenous infusion therapy, significantly impacts therapeutic outcomes, patient satisfaction, cost of care, and provider workload. Here we review the major etiologies of IRP and describe potential pharmacological and nonpharmacological interventions for preventing and managing the condition as well as for improving vascular access health in multiple-drug administration settings. SUMMARY: Many parenterally administered drugs cause phlebitis due to mechanical, chemical, or infectious etiologies. Pharmacists can recommend nonpharmacological strategies to mitigate phlebitis, including -judicious device selection and placement; adjustment of the drug concentration, flow rate, or formulation; infusion site rotation; and use of inline filters to minimize contaminant particulates. Pharmacological treatments for phlebitis include topical, local, and systemic anti-inflammatory and analgesic agents that can reduce symptom severity and prevent further treatment complications or delays. CONCLUSION: Pharmacists can contribute a unique perspective to interprofessional teams tasked with making policy and formulary decisions that minimize the negative impacts of IRP on drug delivery and patient outcomes.

Comparison of Quality of Life and Injection Site Reactions After Switching from Degarelix 80 mg to 480 mg in Advanced Prostate Cancer: A Prospective Trial.

BACKGROUND/AIM: Degarelix has been widely used for prostate cancer; however, injection site reactions (ISRs) can be a clinical issue. We assessed differences in ISR intensity and patient quality of life (QOL) between degarelix 80 mg and 480 mg, a three-month formulation launched in 2020 in Japan. PATIENTS AND METHODS: We prospectively analyzed 25 patients with advanced prostate cancer. ISR intensity and patient QOL were evaluated before and after switching from degarelix 80 mg to 480 mg. A visual analogue scale (VAS) and faces rating scale (FRS) were applied to assess the ISRs. We applied a rating format from the M. D. Anderson Symptom Inventory (MDASI) to assess patient QOL. RESULTS: For degarelix 80 mg and a first dose of 480 mg, the incidence rate of ISRs was 84% and 92%, respectively (p=0.083). ISR pain on the third day after injection scored by VAS was 2.7±2.8 and 5.2±2.7, respectively (p<0.001). Other ISR findings such as redness, induration, swelling, warmth, and itching were significantly worse for degarelix 480 mg than for 80 mg. In the category of patient QOL, interference with activities of daily living such as general activity was significantly worse after degarelix 480 mg (p=0.003). However, 80% of patients were able to continue degarelix 480 mg during the nine months of follow-up. CONCLUSION: Degarelix 480 mg seems to exacerbate pain and other ISR findings, and to reduce patient QOL, compared with degarelix 80 mg. Optimal management of ISRs is essential to maintain patient QOL when using degarelix 480 mg.

Adverse Reactions after BNT162b2 Messenger RNA Vaccination for Coronavirus Disease 2019 in Healthcare Workers Compared with Influenza Vaccination.

This study aimed to compare adverse reactions following BNT162b2 and influenza vaccinations in healthcare workers. This study included healthcare workers who received the BNT162b2 vaccine and/or inactivated influenza vaccine, quadrivalent (IIV4), on 18-29 October 2021 at a tertiary hospital in Korea. IIV4 was administered and BNT162b2 was subsequently administered one week later. The participants responded to a mobile questionnaire regarding adverse events. The overall adverse reaction rates were 90.6% in the BNT162b2 + IIV4 group, 90.4% in the BNT162b2 alone group, and 44.1% in the IIV4 alone group (p < 0.001). Fever occurred in 19.5%, 26.9%, and 3.3% of participants in the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). The most common local and systemic adverse reactions were injection site pain (65.0%) and fatigue (58.6%), respectively. Injection-site pain was experienced by 88.7%, 88.5%, and 37.5% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Fatigue was experienced by 74.8%, 78.8%, and 38.6% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Adverse reactions occurred at a significantly higher frequency after BNT162b2 than after IIV4. The frequency of adverse reactions one week after vaccination with IIV4 and BNT162b2 was not different from that after vaccination with BNT162b2 alone. Therefore, coadministration of influenza vaccine with BNT162b2 can be expected to be safe.

A Systematic Literature Review of Injection Site Pain Perception in Adult Patients Treated with Citrate-Free and Citrate-Containing Biologic Agents.

OBJECTIVE: To investigate injection site pain (ISP) and other injection site outcomes caused by biologics administered alongside citrate-free (CF) and citrate-containing (CC) formulations. METHODS: Electronic literature databases (Medline, Embase, and Cochrane Library) were systematically searched for clinical trials and observational studies reporting on injection site outcomes after subcutaneous administration of biologics. Studies with unknown excipient formulations were excluded. The primary outcome was ISP, and secondary outcomes included any other reported injection site reactions (ISRs). Meta-analysis approaches were used to aggregate evidence identified via the conducted systematic literature review. RESULTS: A total of two observational studies, two cross-over/sequential trials, and three head-tohead comparison trials directly comparing CF with CC biologics were identified, as well as seven placebo-controlled trials. Evidence from five of the seven direct comparison studies suggested reduced pain perception at the injection site when CF formulations were applied. Findings for other ISRs were balanced between both formulations, with slightly favorable results for preparations without citrate. A meta-analysis of placebo-controlled trials found no significant difference between arms with CF formulations and placebo regarding the proportion of patients experiencing ISP (OR 0.62, 95% CI 0.30-1.28). CONCLUSION: Excipient formulations are rarely specified in studies assessing pain and other ISRs of subcutaneously administered biologics. The available data indicate that subcutaneous administration of biologic agents without citrate may be associated with lower pain perception outcomes compared with treatment using CC formulations. Importantly, ISP is influenced by many factors which may have affected the results. More research is needed to assess how formulation excipients influence ISRs.

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.