Occurrence Of Injection Site Reactions Research Articles

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation

ObjectivesThis study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient. Study designWe conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections. ResultsOf a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (n = 24), bruising (n = 4), and atrophy/dimple (n = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections. ConclusionsSubcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046. ImplicationsFrom a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials. Trial registrationRegistered at clinicaltrials.gov no: NCT02817464

PRESTO 2: An International Survey to Evaluate Patients' Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly.

Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited. PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3months in Canada, Ireland, the UK and the USA (planned sample size, 304). the proportion of patients with injection-site pain lasting > 2days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6months. There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6years). Fewer patients had injection-site pain lasting > 2days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients. Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs.

Comparative Efficacy and Safety of Anti-Interleukin-5 Therapies and Placebo in Patients with Uncontrolled Eosinophilic Asthma:

The overall efficacy and safety of anti-interleukin （IL）-5 therapies at currently recommended dosages and administration remain to be fully characterized. The present study was a meta-analysis of Phase 3 trials of the efficacy and safety of anti-IL-5 therapies at the currently recommended dosages and administration compared with placebo in patients with uncontrolled eosinophilic asthma. This meta-analysis complied with the PRISMA guidelines. The primary efficacy outcome was asthma exacerbation rate, and the primary safety outcomes included the incidence rates of all adverse events, asthma worsening, and injection site reactions. A subgroup analysis was also performed according to the type of anti-IL-5 agent. Pooled estimates are presented as rate ratios or relative risks （RRs） with 95% confidence intervals （CIs）. Analyses included intention-to-treat cases. Six randomized controlled trials of anti-IL-5 therapies met the inclusion criteria. The overall rate ratio for asthma exacerbation was 0.54 （95% CI 0.47-0.61）. The RRs （95% CIs） for the incidence of all adverse events, asthma worsening, and injection site reactions compared with placebo were 0.93 （0.89-0.96）, 0.63 （0.56-0.72）, and 1.59 （0.95-2.65）, respectively. The subgroup analysis revealed that the incidence of injection site reactions was significantly higher among mepolizumab- than placebo-treated patients, with an RR of 2.56 （95% CI 1.15-5.68）. These results suggest that anti-IL-5 therapies at the currently recommended dosages and administration are effective and generally well tolerated in patients with uncontrolled eosinophilic asthma. However, the occurrence of injection site reactions warrants specific attention, especially concerning mepolizumab administration.

Evaluation of histopathological findings at the injection site following degarelix administration.

The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.

An approach to local immunotoxicity induced by adjuvanted vaccines

The occurrence of injection site reactions following immunization is the most frequently reported toxicity manifestation of vaccines; however, the different types of local reactions and the different mechanisms involved are still unclear. Here, the current advances in adjuvants and the role that adjuvants play in local reactions are reviewed. The role of adjuvants in the formation of the loco-regional complex (LRC), which consists of the injection site, draining lymphatic vessels and regional lymph nodes, is also discussed. Finally, strategies and recommendations for the rational design of adjuvanted vaccines are discussed, with a particular interest in the reduction of local inflammation.

Réduction des réactions cutanées aux points d’injection avec deux auto-injecteurs chez des patients ayant une sclérose en plaques rémittente débutant un traitement par interféron bêta-1b: étude randomisée en cross-over

To compare occurrence of injection site reactions (ISRs) in patients with relapsing remitting multiple sclerosis (RRMS) newly started on interferon beta 1b (Betaferon), using 3 delivery methods. A randomized, multicenter, phase IV, open label cross-over study was performed in 82 sites in France on 294 patients with RRMS beginning a treatment with interferon beta 1b. For the first month all patients used a standard injection technique. They then used an autoinjector, Betaject or Betaject Light, for one month each, according to the cross-over design. Primary outcome was defined as the percentage of injections sites with ISR evaluated by the investigator. Secondary endpoints included graduation of ISR, using a five-point scale by both investigators and patients, injection related pain assessed by patients, percentage of patients without ISR and a global evaluation by patients of injection devices. The percentage of ISRs were significantly reduced (p<0.0001) when using either Betaject or Betaject light (24.1 percent and 24.1 percent respectively) compared with the standard technique (35.9 percent). No significant difference was seen between the 2 autoinjectors. The mean ISR intensity scores according to physician or patient were significantly reduced (p<0.0001 for each) by the 2 autoinjectors compared to the standard injection technique. No significant difference on the pain scale comparing respectively the standard, Betaject and Betaject light techniques but the mean level of pain was less than 1.2/10. In addition, the percentage of ISR-free patients was significantly lower with the standard injection technique phase (52.4 percent) than with autoinjector use (respectively 68.1 and 66.7 percent). A non significant higher percentage of patients subjectively preferred Betaject (53.7 percent) than to Betaject light (46.3 percent). The main other adverse events reported were flu-like symptoms (30.7 percent), transient and moderate increase of transaminases (4.8 percent) and headache (4.4 percent). We conclude that autoinjector use reduces the occurrence of ISR during IFNB-1b therapy in RRMS.

Safety of High Doses of Influenza Vaccine and Effect on Antibody Responses in Elderly Persons

Immune responses after influenza immunization are reduced in elderly individuals, the group at greatest risk for complications and death after influenza. Improved vaccines are needed to address this problem. Ambulatory individuals 65 years and older (N = 202) were assigned randomly to receive a single intramuscular injection of the 2001-2002 formulation of trivalent inactivated influenza vaccine containing 15, 30, or 60 microg of hemagglutinin per strain (up to 180 microg total per dose) or placebo. Clinical and serologic responses were assessed during the month after immunization. Increasing dosages of vaccine elicited significantly higher serum antibody levels, frequencies of antibody responses, and putative protective titers after vaccination. Mean serum hemagglutination inhibition antibody titers 1 month after immunization in groups given 0-, 15-, 30-, and 60-microg dosages were 23, 37, 50, and 61 against influenza A/H1N1; 43, 86, 91, and 125 against influenza A/H3N2; and 10, 14, 18, and 24 against influenza B, respectively. Mean serum hemagglutination inhibition and neutralizing antibody levels against the 3 vaccine antigens in participants given the 60-microg dosage were 44% to 71% and 54% to 79%, respectively, higher than those in participants given the standard 15-microg dosage, and the 60-microg dosage level nearly doubled the frequency of antibody responses in those whose preimmunization antibody titers were in the lower half of the antibody range. Dose-related increases in the occurrence of injection site reactions were observed (P<.001), but all dosages were well tolerated. The improved immunogenicity of high-dose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.