Background
Hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5–11 years and ...worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.
Methods
The Icatibant Outcome Survey (IOS) is an observational study evaluating the safety, tolerability, and efficacy of icatibant. We conducted descriptive analyses in younger (age < 65 years) versus elderly patients (age ≥ 65 years). Here, we report patient characteristics and safety‐related findings.
Results
As of February 2018, 872 patients with C1‐INH‐HAE type I/II were enrolled, of whom 100 (11.5%) were ≥ 65 years old. Significant differences between elderly versus younger patients, respectively, were noted for median age at symptom onset (17.0 vs 12.0 years), age at diagnosis (41.0 vs 19.4 years), and delay between symptom onset and diagnosis (23.9 vs 4.8 years) (P ≤ 0.0001 for all). Median age at diagnosis was significantly higher in elderly patients regardless of family history (P < 0.0001). Throughout the study, icatibant was used to treat 6798 attacks in 574 patients, with 63 elderly patients reporting 715 (10.5%) of the icatibant‐treated attacks. No serious adverse events (SAEs) in elderly patients were judged to be possibly related to icatibant, whereas two younger patients reported three possibly related SAEs. Excluding off‐label use and pregnancy (evaluated for regulatory purposes), the percentage of patients with at least one possibly/probably related AE was similar for elderly (2.0%) versus younger patients (2.7%). No deaths linked to icatibant treatment were identified. All related events in elderly patients were attributed to general disorders/administration site conditions, whereas related events in younger patients occurred across various system organ class designations.
Conclusions
Elderly patients with C1‐INH‐HAE were significantly older at diagnosis and had greater delay in diagnosis than younger patients. Elderly patients contributed to approximately 10% of the icatibant‐treated attacks. Our analysis found similar AE rates (overall and possibly/probably related) in icatibant‐treated elderly versus younger patients, despite the fact that elderly patients had significantly more comorbidities and were receiving a greater number of concomitant medications. Our analysis did not identify any new or unexpected safety concerns.
Noninvasive imaging using positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT) are considered revolutionized ...approaches to detect bone cancer. Both PET/CT and SPECT/CT technologies have advanced to permit miniaturization, which has provided the advantage of including animals as their own controls in longitudinal studies. The present study was designed to evaluate the potential of PET/CT and SPECT/CT as research tools to detect bone cancer in rats. We used a rat model of bone cancer induced by injecting Walker 256 tumor cells into the femoral cavity. Computed tomography demonstrated that rats presented a solid tumor at 15 days post injection (dpi). However, CT was not an effective method for identifying tumors at an earlier time point (8 dpi), when mechanical hyperalgesia (the most common symptom during bone cancer progression) had already initiated. At this early stage, PET/CT and SPECT/CT analysis detected higher uptake in the injected femur of the tracers 18F-Fluoride and 99mTc-Methyl diphosphonate (99mTc-MDP), respectively. These findings demonstrated for the first time that both 18F-Fluoride PET/CT and 99mTc-MDP SPECT/CT can detect cancer at early stages in rats and advocates for the PET/SPECT/CT as research tools to evaluate bone cancer in further longitudinal studies involving small animals.
Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic ...treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option.
Data on LTP use, attacks, and treatments were recorded. Attack characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP.
Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP. Attack rate, attack severity, and the distribution of attack sites were similar across all types of LTP used, and were comparable to the results found in patients who did not receive LTP. Attacks were successfully treated with icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant injection without C1-INH rescue medication. Treatment outcomes were comparable for breakthrough attacks across all LTP types, and for attacks without LTP.
Patients who use LTP should be aware that breakthrough attacks can occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP should have emergency treatment readily available. Data from IOS show that icatibant is effective for the treatment of breakthrough attacks.
NCT01034969.
Noninvasive imaging using positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT) are considered revolutionized ...approaches to detect bone cancer. Both PET/CT and SPECT/CT technologies have advanced to permit miniaturization, which has provided the advantage of including animals as their own controls in longitudinal studies. The present study was designed to evaluate the potential of PET/CT and SPECT/CT as research tools to detect bone cancer in rats. We used a rat model of bone cancer induced by injecting Walker 256 tumor cells into the femoral cavity. Computed tomography demonstrated that rats presented a solid tumor at 15 days post injection (dpi). However, CT was not an effective method for identifying tumors at an earlier time point (8 dpi), when mechanical hyperalgesia (the most common symptom during bone cancer progression) had already initiated. At this early stage, PET/CT and SPECT/CT analysis detected higher uptake in the injected femur of the tracers
F-Fluoride and
Tc-Methyl diphosphonate (
Tc-MDP), respectively. These findings demonstrated for the first time that both
F-Fluoride PET/CT and
Tc-MDP SPECT/CT can detect cancer at early stages in rats and advocates for the PET/SPECT/CT as research tools to evaluate bone cancer in further longitudinal studies involving small animals.
Dose calibrator linearity testing is indispensable for evaluating the capacity of this equipment in measuring radioisotope activities at different magnitudes, a fundamental aspect of the daily ...routine of a nuclear medicine department, and with an impact on patient exposure. The main aims of this study were to evaluate the feasibility of substituting the radioisotope Fluorine-18 (
18
F) with Technetium-99m (
99m
Tc) in this test, and to indicate it with the lowest operational cost. The test was applied with sources of
99m
Tc (62 GBq) and
18
F (12 GBq), the activities of which were measured at different times, with the equipment preadjusted to measuring sources of
99m
Tc,
18
F, Gallium-67 (
67
Ga), and Iodine-131 (
131
I). Over time, the average deviation between measured and expected activities from
99m
Tc and
18
F were, respectively, 0.56 (±1.79)% and 0.92 (±1.19)%. The average ratios for 99
m
Tc source experimental activity, when measured with the equipment adjusted for measuring
18
F,
67
Ga, and
131
I sources, in real values, were, respectively, 3.42 (±0.06), 1.45 (±0.03), and 1.13 (±0.02), and those for the
18
F source experimental activity, measured through adjustments of
99m
Tc,
67
Ga, and
131
I, were, respectively, 0.295 (±0.004), 0.335 (±0.007), and 0.426 (±0.006). The adjustment of a simple exponential function for describing
99m
Tc and
18
F experimental activities facilitated the calculation of the physical half-lives of the radioisotopes, with a difference of about 1% in relation to the values described in the literature. Linearity test results, when using
99m
Tc, through being compatible with those acquired with
18
F, imply the possibility of using both radioisotopes during linearity testing. Nevertheless, this information, along with the high potential of exposure and the high cost of
18
F, implies that
99m
Tc should preferably be employed for linearity testing in clinics that normally use
18
F, without the risk of prejudicing either the procedure itself or the guarantee of a high-quality nuclear medicine service.
Dose calibrator linearity testing is indispensable for evaluating the capacity of this equipment in measuring radioisotope activities at different magnitudes, a fundamental aspect of the daily ...routine of a nuclear medicine department, and with an impact on patient exposure. The main aims of this study were to evaluate the feasibility of substituting the radioisotope Fluorine-18 ((18)F) with Technetium-99m ((99m)Tc) in this test, and to indicate it with the lowest operational cost. The test was applied with sources of (99m)Tc (62 GBq) and (18)F (12 GBq), the activities of which were measured at different times, with the equipment preadjusted to measuring sources of (99m)Tc, (18)F, Gallium-67 ((67)Ga), and Iodine-131 ((131)I). Over time, the average deviation between measured and expected activities from (99m)Tc and (18)F were, respectively, 0.56 (±1.79)% and 0.92 (±1.19)%. The average ratios for 99(m)Tc source experimental activity, when measured with the equipment adjusted for measuring (18)F, (67)Ga, and (131)I sources, in real values, were, respectively, 3.42 (±0.06), 1.45 (±0.03), and 1.13 (±0.02), and those for the (18)F source experimental activity, measured through adjustments of (99m)Tc, (67)Ga, and (131)I, were, respectively, 0.295 (±0.004), 0.335 (±0.007), and 0.426 (±0.006). The adjustment of a simple exponential function for describing (99m)Tc and (18)F experimental activities facilitated the calculation of the physical half-lives of the radioisotopes, with a difference of about 1% in relation to the values described in the literature. Linearity test results, when using (99m)Tc, through being compatible with those acquired with (18)F, imply the possibility of using both radioisotopes during linearity testing. Nevertheless, this information, along with the high potential of exposure and the high cost of (18)F, implies that (99m)Tc should preferably be employed for linearity testing in clinics that normally use (18)F, without the risk of prejudicing either the procedure itself or the guarantee of a high-quality nuclear medicine service.
Background
Icatibant is a bradykinin B2‐receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1‐inhibitor deficiency. Treatment is not adjusted by body weight ...however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real‐world safety and effectiveness of icatibant.
Methods
Attack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI.
Results
Data from 2697 icatibant‐treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9–83.8%) were treated with a single icatibant injection without the need for rescue with plasma‐derived C1‐inhibitor (pdC1‐INH), regardless of BMI. Patients with obese BMI used pdC1‐INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal).
Conclusion
Overall, icatibant was comparatively effective in treating attacks in patients across all BMI groups.
Trial registration NCT01034969.
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