Bimonthly Injections Research Articles

Comparison Of Contraceptive Injection Between Monthly, Bimonthly And TriMonthly Combination Of Medroxyprogesterone Acetate With Estradiol Cypionate: Hemodynamic Effect, Weight Gain And Compliance Of Multicenter Clinical Trials, Phase III Randomization Study

Background: Monthly contraceptive injection, which consists of MPA (medroxyprogesterone acetate) mixture with a low-dose estrogen preparate (25 mg MPA and 5 mg estradiol cipionate) is commonly used in Indonesia. It is less practical, because the subjects must visit health services every month. To reduce the imprac- ticality, it has been developed a bi-monthly contraceptive injection of 65 mg MPA and 7.5mg estradi- ol cypionate and a trimonthly contraceptive injection of 120 mg MPA and 10 mg estradiol cypionate. Method: This is a randomized controlled clinical trial - open-label conducted from March 2013 to May 2017 with a total sample of 1080. The study subjects consist of 3 groups. The first group was treated with bi-monthly injections (Injection A), the second group was treated with trimonth- ly injections (Injection B) and the third group was treated with monthly injections (Injection C). The blood pressure, pulse rate and body weight were measured since initial treatment and during each visit for 1 year of treatment. This clinical trial has been registered in the National Agency of Drug and Food Control of the Republic of Indonesia with clinical trial number: PN.01.02.1.31.10.12.6669 Result: No significant differences of blood pressure between each group and during 1 year of in- jection in each group. We found significant differences of weight gain in each group during 1 year of injection (p<0.01), but we did not find significant difference of weight gain be- tween each group. Injection B shows the lowest percentage of dropout cases (1,21%). Conclusion: It can be concluded that bi-monthly injections and trimonth- ly injections are more effective than monthly injections for 12 months of use. They are safe to use, convenient in reducing doctor visits and have a high acceptability.

Long-acting injectable cabotegravir: implementation science needed to advance this additional HIV prevention choice.

Long-acting injectable cabotegravir: implementation science needed to advance this additional HIV prevention choice.

Cost of Ranibizumab Port Delivery System vs Intravitreal Injections for Patients With Neovascular Age-Related Macular Degeneration

The study team investigated costs associated with the ranibizumab port delivery system (PDS) for neovascular age-related macular (nAMD), an alternative to conventional intravitreal anti-vascular endothelial growth factor (VEGF) injections. To investigate costs of intravitreal anti-VEGF injections vs ranibizumab PDS for patients with neovascular AMD (nAMD). This cost analysis used trial data and Medicare reimbursement rates and included patients with nAMD who were receiving ranibizumab, aflibercept, bevacizumab injections, or ranibizumab PDS. The number of intravitreal ranibizumab, aflibercept, and bevacizumab injections to break even with costs of ranibizumab PDS. Total direct medical costs over 1 year and 5 years for the ranibizumab PDS arm with refills at fixed 6-month intervals compared with monthly or bimonthly injections were calculated using Medicare rates. Scenario and sensitivity analyses accounted for uncertainty and variation. The mean (SD) number of ranibizumab, aflibercept, and bevacizumab injections to break even with the cost of ranibizumab PDS with 1 refill was 10.8 (1.3), 9.3 (1.1), and 34.5 (4.2), respectively. Ranibizumab PDS with fixed 6-month refills over 1 year cost $21 016 ($2102). Comparatively, monthly intravitreal ranibizumab cost $1943 (95% CI, -$3047 to $6932; P = .34) more, aflibercept cost $5702 (95% CI, $253-$11 151; P = .04) more, and bevacizumab cost $16 732 (95% CI, -$20 170 to -$13 294, P < .001) less. For bimonthly injections, aflibercept cost $7658 (95% CI, -$11 649.52 to -$3665.61; P = .006) less. Over 5 years, monthly intravitreal ranibizumab projected to cost $25 581 (95% CI, $2275-$48 887; P = .04) more, aflibercept cost $44 374 (95% CI, $18 623-$70 125; P = .008) more, and bevacizumab cost $67 793 (95% CI, -$82 501 to -$53 085; P < .001) less than PDS with fixed refills (mean [SD] cost, $89 218 [$8921]). For bimonthly injections, aflibercept cost $22 422 (95% CI, -$40 287 to -$45,56; P = .03) less. In scenario analyses, ranibizumab PDS with refills as needed offered cost savings compared with real-world intravitreal ranibizumab or aflibercept use at 5 years but not at 1 year. In this cost analysis, ranibizumab PDS with 1 refill cost more than intravitreal ranibizumab or aflibercept injections if less than or equal to approximately 11 or 10 injections, respectively, are required within the first year. Long term, if less than 4.4 and 3.8 injections are needed per refill, intravitreal ranibizumab and aflibercept is lower cost. Ranibizumab PDS costs more than intravitreal bevacizumab injections throughout scenarios.

Resident Perspectives

Resident Perspectives

Associations of hypertension Diabetes Smoking History and SNPs with Responses to Aflibercept Treatment for tAMD and PCV

Purpose: To determine the correlation between therapeutic effects of IVA treatment on typical AMD (tAMD), and polypoidal choroidal vasculopathy (PCV) and the history of hypertension, diabetes mellitus, smoking history and single nucleotide polymorphisms (SNPs).Methods: Prospective, interventional study. Subjects were assigned to 125 untreated patients with exudative AMD (tAMD: 58 patients, PCV: 67 patients, male: 91:34, mean age 73.4 years). Among the tAMD patients, there were 28 bimonthly injections 30 who received pro re nata (PRN) injections after three monthly injections. Among the PCV patients, 33 were treated with bimonthly injections and 34 received PRN injections after three monthly injections. Therapeutic effects were evaluated by best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (CCT), and exudative change after 3 months and 1 year from initial treatment, and also the history of hypertension, diabetes mellitus, smoking and five SNPs (rs10490924, rs800292, rs699947, rs1061170, rs13278062).Results: Improvements of BCVA, CRT were observed in all groups at 1 year after initial treatment. The one-yearchange in CRT showed significant improvement in nonsmokers than smokers in tAMD. The one-year change in CRT indicated a significant improvement in non-diabetic patients in PCV. There was more exudation at both 3 months and 1 year who had smoking history in tAMD. With respect to the rs1061170 mutation of tAMD, in the case with TT type, significant residual exudation was noted at both 3 and 12 months.Conclusions: The history of smoking and diabetes could be influence to IVA treatment for AMD.

Experiences of using Aflibercept in diabetic macular edema treatment: data from routine clinical practice

Purpose. To assess the effectiveness and safety of intravitreal aflibercept injections in clinically significant diabetic macular edema (DME) in a routine clinical practice.Material and methods. This was a prospective, observational, single-center study. During the study, anti-VEGF treatment naïve patients with clinically significant DME received five monthly intravitreal injections of aflibercept 2 mg followed by bimonthly injections. The observation period was 1 year.Results. The study included 11 eyes of 10 patients with clinically significant DME. Use of 8 intravitreal aflibercept injections resulted in central retinal thickness (CRT) reduction by 50 % from the baseline within 1 year of therapy. CRT decreased on average from 446.18 ± 106.88 μm to 226.27 ± 44.56 μm by the end of observational period. In addition, an increase in visual acuity was observed from an average from 0.33 ± 0.22 at the start of therapy to 0.62 ± 0.33 at the end of the observation. Serious adverse events over the entire period of treatment were not observed.Conclusion. Aflibercept showed high efficacy and safety in the treatment of clinically significant DME in routine clinical practice. To obtain optimal functional and morphological results in the treatment of patients with DME, it is necessary to start therapy with 5 loading intravitreal aflibercept injections.

Real-World Results of Aflibercept versus Ranibizumab for the Treatment of Exudative AMD Using a Fixed Regimen

Intravitreal injections of antivascular endothelial growth factors have been considered a milestone in the treatment of neovascular age-related macular degeneration (nAMD). However, the increasing incidence of AMD and the burden of visits and injections overcharge both the patient and the healthcare systems. Real-world solutions depend on treatment protocols aimed at optimizing the number of clinical visits while guaranteeing good functional outcomes. We performed a retrospective analysis of 72 eyes from 63 naïve patients diagnosed with nAMD that underwent a fixed intravitreal protocol consisting of bimonthly injections after a three-month loading dose, with either Aflibercept or Ranibizumab (no predefined criteria for treatment selection). Best corrected visual acuity (BCVA) and optical coherence tomography were analyzed at baseline and during follow-up clinical visits (months 3, 6, 12, and 18). From the included participants, 42 followed a fixed regimen with Aflibercept and 30 with Ranibizumab. At the 12-month visit, there was not a statistically significant difference in the mean change of BCVA between the two groups (p=0.121); however, the mean difference in the central retinal thickness was significantly superior in the Aflibercept group (-142.2 versus -51.5, p=0.011). The described fixed regimen seems to be efficient in the treatment of nAMD in a clinical practice setting.

Uveitis in sporadic Blau syndrome: Long-term follow-up of a refractory case treated successfully with adalimumab

The classic entity of autosomal dominant Blau syndrome (BS) consists of arthritis, dermatitis, and uveitis, occurring as a result of mutations in the NOD2 gene pattern recognition receptor. Sporadic cases are those in which no known gene mutation is identifiable. Uveitis in BS can be refractory to conventional therapy. We report a case of sporadic Blau uveitis managed with adalimumab monotherapy after failing to respond to topical steroids, systemic steroids, methotrexate, and infliximab therapy sequentially. Uveitis resolved completely with adalimumab and the patient has had a disease-free period over a 2-year follow-up with bi-monthly injections for arthritis control.

Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) study.

PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.

How effective are immune modulator injections of the globe in patients with wet macular degeneration?

EVIDENCE-BASED ANSWER For patients with wet macular degeneration, intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) immune modulators such as ranibizumab, bevacizumab, or pegaptanib can prevent loss of visual acuity and, in some cases, improve visual acuity (SOR: A, meta-analysis). A newer agent, aflibercept, is noninferior to ranibizumab with the advantage of bimonthly injections instead of monthly (SOR: B, lower quality meta-analysis).

401. AAV Therapy Attenuates Respiratory Dysfunction and Glycogen Accumulation in a Murine Model of Glycogen Storage Disease Type II

Cardiac dysfunction and respiratory muscle weakness are primary features in patients with early onset Pompe disease. To reduce the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa-/- mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9) or bi-monthly injections of recombinant human GAA (ERT). Cardiac function and morphology was assessed one and three months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at three months post-treatment in all groups. Gaa-/- animals receiving either AAV9 or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9 treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc) at three months post-injection. Neither AAV9 nor ERT therapy altered minute ventilation during quiet breathing (eupnea). However, breathing frequency and expiratory time were significantly improved in AAV9 animals. Glycogen deposition was significantly elevated in Gaa-/- and ERT but not AAV9 when compared to control animals. These results indicate systemic delivery of either strategy improves cardiac function but improvement in respiratory parameters and glycogen reduction are limited to AAV9 therapy at three-months post treatment in a murine model of Pompe disease.

Bimonthly injections of ranibizumab for age-related macular degeneration

To evaluate the efficacy of bimonthly intravitreal injections of ranibizumab for age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in a pilot study. This study was a prospective, interventional case series. Thirty eyes of 30 patients received prospectively at least three bimonthly intravitreal injections of ranibizumab (0.5 mg/0.05 ml) without loading doses. The best-corrected visual acuity (BCVA) and the central retinal subfield thickness (CRST) were measured before and monthly after the injections. Twenty-eight patients received the three planned injections; one patient refused the third injection, one patient did not receive the third injection because blood pressure was raised, and one patient received a rescue injection at month 5 because of increased retinal thickness. The mean logarithm of the minimum angle of resolution (logMAR) BCVA was 0.44 ± 0.37 before treatment and significantly improved to 0.25 ± 0.34 at month 6 (p < 0.001). The mean CRST was 335 ± 85.9 μm before treatment and decreased significantly to 261 ± 78.1 μm at month 6 (p < 0.001). Nine of 30 patients received six planned injections for 12 months. The mean logMAR BCVA was 0.38 ± 0.39 before treatment and significantly improved to 0.18 ± 0.33 at month 12 (p = 0.005). The mean CRST was 360 ± 110.8 μm before treatment and decreased significantly to 249 ± 57.0 μm at month 12 (p = 0.025). Bimonthly injections of ranibizumab may be effective for treating AMD and PCV.

Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration

To evaluate vascular endothelial growth factor (VEGF) and ranibizumab concentrations in eyes with age-related macular degeneration (AMD) after monthly and bimonthly intravitreal ranibizumab (IVR) injections. Aqueous humor samples were obtained from 26 eyes with AMD before and after IVR injections. Nine eyes received three monthly injections and 17 eyes received two bimonthly injections. The VEGF and ranibizumab concentrations were measured by enzyme-linked immunosorbent assay. The aqueous VEGF concentrations in the monthly injection group decreased below the lowest detectable limit in eight of nine eyes 1 month after the first injection and seven of nine eyes 1 month after the second injection (P < 0.001, mean baseline value, 94.7 pg/ml); the aqueous VEGF concentrations in the bimonthly injection group decreased below the lowest detectable limit in two of 17 eyes 2 months after the first injection (P < 0.001, mean baseline value, 152.4 pg/ml). The mean aqueous ranibizumab concentrations with monthly injections were 71.2 ng/ml 1 month after the first injection, and 96.3 ng/ml 1 month after the second injection. The mean aqueous ranibizumab concentrations in the bimonthly injection group were 2.5 ng/ml in 15 of 17 eyes, and below the lowest detectable limit in two of 17 eyes 2 months after the first injection. In this pilot study with limited follow-up, intravitreal injection of ranibizumab can suppress aqueous VEGF completely for 1 month in most cases. Its effect does not last for 2 months enough to suppress VEGF completely in most cases, although aqueous VEGF at 2 months after intravitreal injection of ranibizumab is less than that before injection in most cases.

Abstract 4748: Therapy model for advanced intracerebral B16 mouse melanoma using radiosurgery combined with immunotherapy.

Abstract A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8) were further suppressed by a single ip injection of a Treg depleting Mab given two days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The results of seven independent experiments were similar to the combined result: the Median (Days) [SD/Total N] of survival went from 15[1.09/62] (No Treatment Control) to 35.8[8.8/58] (Radiosurgery-Only) to 52.5[13.5/57] (Radiosurgery Plus Immunotherapy); Radiosurgery-Only and Radiosurgery Plus Immunotherapy groups were highly distinct from Controls as well as from one another (p&amp;lt;0.0001). Within two weeks after immunization, tumors in mice receiving Radiosurgery Plus Immunotherapy were significantly smaller than tumors in mice treated only with Radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon Y production when cultured with syngenic tumor cells. We hypothesize that our model will be useful for the development and testing of novel combination therapies for brain tumors. Citation Format: Henry M. Smilowitz, Dan Sasso, Edward W. Lee, Peggy Micca, Gyuhyeong Goh, F Avrahamn Dilmanian. Therapy model for advanced intracerebral B16 mouse melanoma using radiosurgery combined with immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4748. doi:10.1158/1538-7445.AM2013-4748

A descriptive, open-label, long-term follow-up survey of psychotic patients receiving risperidone long-acting injectable: Preliminary results

Objective. To assess clinical development in patients with psychotic disorders who received risperidone long-acting injectable (RLAI) in combination with psychosocial interventions as part of daily clinical practice in France. Methods. In this 18-month survey, patients were started on bi-monthly RLAI injections and integrated in a psychosocial treatment programme. Clinical progression was evaluated using the Clinical Global Impression of Severity (CGI-S) and Global Assessment of Functioning (GAF) scales. In addition, data on patient characteristics, adherence, RLAI dosage, concomitant medications and rates and durations of hospitalization were collected. Results. Of the total of 120 patients included in the survey, 95 (79.2%) had previously received other treatments. Non-adherence was the most frequently reported reason for changing to RLAI (93 patients, 97.9%). With RLAI treatment, mean CGI-S scores improved from 5.6±0.5 at baseline to 3.6±1.1 at 18 months, whilst mean GAF scores increased from 34.0±12.7 to 67±13.5 (both P<0.0001). Furthermore, patients had fewer and shorter hospitalizations during the 18 months of RLAI treatment, compared to the preceding 18 months. Conclusions. Patients with psychotic disorders benefited from RLAI treatment in combination with psychosocial interventions, as shown by improvements in their clinical status and functioning and reduced hospitalization rates.

The presence of intervening sequences in the alpha-fetoprotein gene of the mouse.

The presence of intervening sequences in the alpha-fetoprotein gene of the mouse.