Biologics in therapy最新文献

Introduction: This study was conducted using an integrated retrospective database to evaluate the effectiveness of Omnitrope(®) (Sandoz) on children with growth hormone deficiency (GHD), idiopathic short stature (ISS), and Turner Syndrome (TS) who switched from a non-Omnitrope recombinant human growth hormone (rhGH) preparation during routine clinical care.

Methods: This was a retrospective study which identified patients with GHD, ISS, and TS during the study time period of January 1, 2006 and July 31, 2011. Patients were included if they switched to Omnitrope from another non-Omnitrope rhGH therapy during the study time period, were <18 years of age at time of switch, and on a prior rhGH therapy for at least 15 months pre-switch and on Omnitrope for 15 months post-switch. Auxological parameters (height, height standard deviation score [HSDS], height velocity [HV], and height velocity standard deviation score [HVSDS]) were evaluated during post-switch.

Results: One hundred and three patients were identified: GHD (n = 57), ISS (n = 26), and TS (n = 20). There was continuous growth in height for all 103 patients with an average rate of 6.52 cm over the 15-month post-switch period. Patients with GHD grew an average rate of 6.30 cm, patients with ISS grew an average rate of 6.58 cm, and patients with TS grew an average rate of 6.52 cm over the 15-month post-switch period. The average rate of HSDS was increased by 0.04 for all patients. The HV and HVSDS demonstrated the expected decline with advancing age and prolonged duration of treatment.

Conclusions: The growth trajectories of rhGH-treated patients were not negatively impacted by switching to Omnitrope and growth rates remained as expected prior to the switch.

Introduction: The occurrence of atypical femur fractures (AFFs) in patients on prolonged bisphosphonate treatment has been gaining medical attention, but the use of pharmacotherapy for these fractures has not been explored in detail. The authors describe a case of AFFs successfully treated with once-weekly administration of 56.5 μg teriparatide (TPTD).

Case presentation: The patient was a 74-year-old female patient who had been taking alendronate for approximately 6 years and who suffered with a fall while walking. X-rays revealed a subtrochanteric right femur fracture. The contralateral femur showed cortical thickening and a transverse radiolucent fracture line. Based on these specific features, the patient was diagnosed with AFF. The patient underwent osteosynthesis with intramedullary nailing for the right fracture. Alendronate treatment was discontinued. Low-intensity pulsed ultrasonography therapy did not affect the healing of the fracture with delayed union, even after 3 months of application. Prophylactic osteosynthesis was performed for the subtrochanteric left femur. Bone tissue collected from the left fracture site during surgery showed severe suppression of bone turnover. Union of bilateral femurs was achieved after 3 months of a once-weekly administration of TPTD.

Conclusion: Once-weekly TPTD treatment is shown to be beneficial for improving the healing of AFFs showing delayed union.

Introduction: Standard treatment for patients with primary immunodeficiency (PID) is monthly intravenous immunoglobulin (IVIG), or weekly/biweekly subcutaneous immunoglobulin (SCIG) infusion. We used population pharmacokinetic modeling to predict immunoglobulin G (IgG) exposure following a broad range of SCIG dosing regimens for initiation and maintenance therapy in patients with PID.

Methods: Simulations of SCIG dosing were performed to predict IgG concentration-time profiles and exposure metrics [steady-state area under the IgG concentration-time curve (AUC), IgG peak concentration (C max), and IgG trough concentration (C min) ratios] for various infusion regimens.

Results: The equivalent of a weekly SCIG maintenance dose administered one, two, three, five, or seven times per week, or biweekly produced overlapping steady-state concentration-time profiles and similar AUC, C max, and C min values [95% confidence interval (CI) for ratios was 0.98-1.03, 0.95-1.09, and 0.92-1.08, respectively]. Administration every 3 or 4 weeks resulted in higher peaks and lower troughs; the 95% CI of the AUC, C max, and C min ratios was 0.97-1.04, 1.07-1.26, and 0.86-0.95, respectively. IgG levels >7 g/L were reached within 1 week using a loading dose regimen in which the weekly maintenance dose was administered five times in the first week of treatment. In patients with very low endogenous IgG levels, administering 1.5 times the weekly maintenance dose five times in the first week of treatment resulted in a similar response.

Conclusions: The same total weekly SCIG dose can be administered at different intervals, from daily to biweekly, with minimal impact on serum IgG levels. Several SCIG loading regimens rapidly achieve adequate serum IgG levels in treatment-naïve patients.

Introduction: Inadequately controlled asthma is associated with increased healthcare resource utilization. The eXpeRience registry was initiated to evaluate real-world outcomes in patients receiving omalizumab for uncontrolled persistent allergic asthma. The current analysis of data from the eXpeRience registry focuses on healthcare resource utilization and on absences from work or school.

Methods: The eXpeRience was a 2-year, multinational, non-interventional, observational registry conducted to investigate real-world outcomes among patients receiving omalizumab in accordance with country-specific prescribing criteria for the treatment of uncontrolled persistent allergic asthma. Asthma-related healthcare resource utilization (hospitalizations, emergency room visits or unscheduled-asthma-related doctor visits or interventions) and absences from work or school were assessed pre-treatment (12-month data were collected retrospectively at baseline) and at months 12 and 24 after the initiation of omalizumab treatment. Serious adverse event (SAE) data were also assessed.

Results: A total of 943 patients (mean age 45 years; female 65%) were enrolled in the registry. Overall, the mean (standard deviation [SD]) number of asthma-related medical healthcare uses per patient decreased from 6.2 (6.97) during the pre-treatment period to 1.0 (1.96) and 0.5 (1.28) at months 12 and 24, respectively. The mean (SD) number of work or school days missed due to asthma was also lower at months 12 (3.5 [17.28] and 1.6 [4.28], respectively) and 24 (1.0 [4.66] and 1.9 [5.46], respectively) compared with the pre-treatment period (26.4 [49.61] and 20.7 [27.49], respectively). The nature and frequency of SAEs in the eXpeRience registry were comparable to that seen in interventional clinical trials with omalizumab.

Conclusion: The results of the eXpeRience registry indicate that omalizumab is associated with reductions in healthcare utilization, and in the number of days of absence from work or school, in patients with uncontrolled persistent allergic asthma in the real-world setting.

Funding: Novartis Pharma AG, Basel, Switzerland.

Background: This prospective, open-label, non-comparative, multicentre, long-term phase IV study is examining the efficacy and safety of somatropin [recombinant human growth hormone (rhGH)] in short children born small for gestational age (SGA) and its impact on the incidence of diabetes. This report is the first interim analysis of patients who have completed 1 year of treatment.

Methods: A total of 278 pre-pubertal patients were enrolled. Key eligibility criteria included height standard deviation score (HSDS) <-2.5; parental adjusted SDS <-1; birth weight and/or length <-2 SD and failure to show catch-up growth by ≥4 years of age. Patients were treated with rhGH 0.035 mg/kg/day. The primary objective was to evaluate the long-term effect of rhGH on carbohydrate metabolism [including fasting glucose, stimulated glucose (2-h oral glucose tolerance test, OGTT) and glycated haemoglobin (HbA1c)]. Secondary objectives included evaluation of height parameters [body height, HSDS, height velocity (HV), HVSDS]; insulin-like growth factor 1 (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) serum levels during treatment; and incidence and severity of adverse events (AEs).

Results: None of the children developed diabetes mellitus within the first year of treatment. Mean levels of fasting glucose, HbA1c and 2-h OGTT values remained stable during the study period. Treatment with rhGH was effective, as documented by all height parameters. Mean HSDS improved from -3.39 at baseline to -2.57 at Year 1. Mean HV increased markedly from 4.25 cm/year at baseline to 8.99 cm/year during the first year. Similarly, mean peak-centred HVSDS increased from -2.13 at baseline to +4.16 at Year 1. Mean IGF-I SDS and IGFBP-3 SDS also increased within the first year (by +1.80 and +0.41, respectively). 13 patients (4.7%) did not respond adequately to treatment (HVSDS <1); they were withdrawn from the study. In total, 192 children (69.3%) experienced treatment-emergent AEs; most (98.7%) were mild-to-moderate, and the majority (96.5%) were unrelated to study treatment.

Conclusion: This interim analysis shows that short children born SGA can be effectively and safely treated with rhGH and that rhGH treatment has no major impact on carbohydrate metabolism after the first year of treatment.

Introduction: Hemolysis is considered a class effect and a rare adverse event that can occur following therapy with human normal immunoglobulin for intravenous administration [i.e., intravenous immunoglobulin (IVIG)]. Anti-A/B isoagglutinins (also referred to as isohemagglutinins) originating from donor plasma are present in polyvalent immunoglobulin G (IgG) products and are considered a probable risk factor for hemolysis. We hypothesized that, by excluding plasma from donors with high isoagglutinin titers, the final IVIG product would have a meaningful reduction in anti-A/B isoagglutinin titers.

Methods: A method for screening donor plasma for anti-A isoagglutinins using an automated indirect agglutination test (IAT) was developed. A cut-off for donor plasma exclusion was defined. Industry-scale donor plasma pools and final IVIG product were prepared according to the manufacturing process of Privigen(®) (CSL Behring, Berne, Switzerland; human 10% liquid IVIG). Anti-A/B isoagglutinin content in pooled plasma and final IVIG product was measured by IAT, direct agglutination test, and a flow cytometry-based assay [fluorescence-activated cell sorting (FACS) anti-A].

Results: Screening of plasma from 705 donors identified 48 (6.8%) donors with high anti-A isoagglutinin titers in plasma (IAT agglutination score ≥2+ in a 1:200 pre-dilution). Exclusion of plasma from these donors resulted in a one-titer-step reduction of anti-A isoagglutinin in pooled plasma, confirmed by a twofold anti-A isoagglutinin concentration reduction measured by FACS anti-A (1,352 vs. 2,467 µg/g IgG). When the same screening and exclusion were applied to industrial-scale plasma pools (resulting in the exclusion of plasma from 5% of donors), anti-A isoagglutinins were reduced by one titer step in the final IVIG product. Anti-B isoagglutinins were also reduced by one titer step, as many donors with high anti-A isoagglutinins also have high anti-B.

Conclusion: Reduction of anti-A/B isoagglutinin titers in IVIG products on an industrial scale is feasible through implementation of anti-A donor screening, which may reduce the risk of hemolysis following IVIG therapy.