Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Purpose

The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.

Procedures

Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).

Results

The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9?±?1.8 and 2.53?±?0.67 % of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.

Conclusions

Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

     

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up

Introduction

The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.

Methods

Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.

Results

At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.

Conclusion

In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.

Trial Registration

ClinicalTrials.gov identifier, NCT02868190.

Funding

Glaukos Corporation, San Clemente, CA.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

The Effectiveness of Trimetazidine Treatment in Patients with Stable Angina Pectoris of Various Durations: Results from the CHOICE-2 Study

Introduction

Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease.

Methods

CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina.

Results

A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration.

Conclusion

TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life.

Funding

Servier.

Trial Registration

ISRCTN identifier ISRCTN65209863.

Plain Language Summary

Plain language summary available for this article.

     

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn’s Disease Patients Stratified by Age

Introduction

The efficacy and safety of vedolizumab, a gut-selective α₄β₇ integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18–80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.

Methods

Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.

Results

At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn’s disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person–years) and adverse events leading to hospitalization (14.8 per 100 person–years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.

Conclusions

The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.

Funding

Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

MRI characteristics of proctitis in Crohn’s disease on perianal MRI

Purpose

Multiple features have been described for assessing inflammation in Crohn’s disease (CD) in MR enterography, but have not been validated in perianal magnetic resonance imaging (MRI). Retrospectively, we studied which MRI features are valuable in assessing proctitis.

Materials and methods

CD patients (≥18 years) who underwent colonoscopy (reference standard) and perianal fistula MRI within 8 weeks were included. Seventeen MRI features were blindly scored by three observers and correlated to endoscopy (regression analysis). Reproducibility (multirater kappa, intraclass correlation coefficient) was determined for all three observer pairs. MRI features were considered relevant when significantly correlated to endoscopy for ≥2 observers, and reproducibility was ≥0.40 for ≥2 observer pairs.

Results

Perianal MRI of 58 CD patients were included. Wall thickness, rectal mural fat, creeping fat, and size of mesorectal lymph nodes showed a significant correlation with endoscopy for ≥2 observers (p = 0.000–0.023, p = 0.011–0.172, p = 0.007–0.011 and p = 0.000–0.005, respectively) with a kappa/intraclass correlation coefficient of ≥0.60 for ≥2 observer pairs. Perimural T2 signal and perimural enhancement significantly correlated to endoscopy (all p values ≤0.05) for all three observers and the reproducibility was ≥0.40 for ≥2 observer pairs. Mural T2 signal and degree and pattern of T1 enhancement showed significant correlation to endoscopy for two observers, but with poor to moderate reproducibility.

Conclusion

Wall thickness, mural fat, and mesorectal features (perimural T2 signal, perimural enhancement, creeping fat, and size of mesorectal lymph nodes) had significant correlation to endoscopy and were reproducible in diagnosing proctitis. Some established luminal features in MRE were considered not useful.

     

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale,Prospective, Single-Cohort ANOUVEAU Study

Introduction

The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan.

Methods

Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness.

Results

Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%.

Conclusions

Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA.

Funding

AbbVie GK and Eisai Co., Ltd.

Trial Registration

ClinicalTrials.gov identifier, NCT01346488.

     

Arthroskopische Therapie der Kniesteife

Background

Knees with a limited range of motion caused by intraarticular scars benefit from arthroscopic arthrolysis. Usually these scars result from previous surgery, severe trauma with damage of intraarticular structures.

Objectives

The aim of this procedure is to improve the patients’ range of motion which is necessary for activities of work and daily life. Scar tissue is debrided and resected arthroscopically with a radiofrequency device, a shaver or a punch.

Indications

Indications are a flexion deficit of max. 40°, an extension deficit of max. 20°, reduced mobility of patella, intraarticular reason for limited range of motion, cyclops after anterior cruciate liagment reconstruction, fibrotic Hoffa fat pad.

Contraindications

Contraindications are an extraarticular origin of limited range of motion (e.?g. fibrotic quadriceps muscle), local and general infection, major osteoarthritis, noncompliance, complex regional pain syndrome type I.

Postoperative management

A continuous physical therapy to maintain range of motion is essential. If necessary, continuous passive motion is implemented. Pain adapted weight-bearing should be used for mobilization. A sufficient oral and (when indicated) regional pain management is important to guarantee the benefit of the surgery.

Results

Patients with a lack of mobility of the knee gain a significantly increased range of motion by this arthroscopic procedure. Because of the minimal invasiveness, trauma of surgery and risk of infection are reduced. In many cases the function of the knee joint can be completely restored or at least improved considerably. Complications such as early osteoarthritis can be avoided.

     

Impact of delay on telesurgical performance: study on the robotic simulator dV-Trainer

Purpose

To determine the impact of communication latency on telesurgical performance using the robotic simulator dV-Trainer\(^{\textregistered }\)

Methods

Surgeons were enrolled during three robotic congresses. They were randomly assigned to a delay group (ranging from 100 to 1000 ms). Each group performed three times a set of four exercises on the simulator: the first attempt without delay (Base) and the last two attempts with delay (Warm-up and Test). The impact of different levels of latency was evaluated.

Results

Thirty-seven surgeons were involved. The different latency groups achieved similar baseline performance with a mean task completion time of 207.2 s (\(p>0.05\)). In the Test stage, the task duration increased gradually from 156.4 to 310.7 s as latency increased from 100 to 500 ms. In separate groups, the task duration deteriorated from Base for latency stages at delays \(\ge \)300 ms, and the errors increased at 500 ms and above (\(p\,<\) 0.05). The subjects’ performance tended to improve from the Warm-up to the Test period. Few subjects completed the tasks with a delay higher than 700 ms.

Conclusion

Gradually increasing latency has a growing impact on performances. Measurable deterioration of performance begins at 300 ms. Delays higher than 700 ms are difficult to manage especially in more complex tasks. Surgeons showed the potential to adapt to delay and may be trained to improve their telesurgical performance at lower-latency levels.

     

Bacterial ventilator-associated pneumonia: bronchoalveolar lavage results are not influenced by dilution

Objective

This study was designed to determine if bronchoalveolar lavage (BAL) quantitative culture results can be used confidently for the diagnosis of bacterial ventilator-associated pneumonia (VAP) without taking dilution into account.

Design

Prospective observational cohort study.

Setting

A 12-bed medical ICU in a teaching hospital.

Patients

A total of 241 BAL (three 50-mL aliquots) were performed in 127 patients presenting a suspicion of VAP.

Interventions

All consecutive adults who were ventilated more than 48 h were included if VAP was clinically suspected. A dilution factor, k, was developed according to the formula: dilution factor k = concentration of urea in plasma/concentration of urea in lavage fluid recovered. Using this dilution factor, the quantitative bacterial counts were interpreted accordingly with a corrected positive threshold at 10⁵ colony forming unit (CFU) mL^?1.

Measurements and results

Eighty-nine BAL with at least one micro-organism ≥10⁴ CFU mL^?1 were identified (37%). In 176 BAL (73%), k ranged from 10 to 100. Median k was 24.4 (9.7–40.2) in VAP group and 24.6 (13.1–57.8) in patients without pneumonia (NS). Among the 25 BAL with micro-organism counts of 10⁴ CFU mL^?1, 3 had a dilution factor lower than 10, resulting in corrected counts below the threshold of 10⁵ CFU mL^?1. Two out of 15 patients with micro-organism counts of 10³ CFU mL^?1 had corrected micro-organism counts of 10⁵ CFU mL^?1. Finally, only five BAL (2.1%) were misclassified when the dilution correction factor was applied.

Conclusions

Using urea as dilution factor, we showed that BAL dilution variations did not alter the interpretation of BAL quantitative bacterial culture when administrating three aliquots of 50 mL of saline.

     

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

Purpose

To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.

Main outcomes

We included 1899 patients with ARDS in this study. The relationship between maximum PaCO₂ in the first 48 h and mortality suggests higher mortality at or above PaCO₂ of ≥50 mmHg. Patients with severe hypercapnia (PaCO₂ ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO₂/FiO₂ ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).

Conclusions

Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.

Trial registration

Clinicaltrials.gov identifier, NCT01093482.

     

Characterization of “γ-Eye”: a Low-Cost Benchtop Mouse-Sized Gamma Camera for Dynamic and Static Imaging Studies

Purpose

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging.

Procedures

The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes.

Results

The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans.

Conclusions

Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.

     

Distribution of lung ventilation in spontaneously breathing neonates lying in different body positions

Objective

The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography (EIT). Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy.

Design

Prospective study.

Setting

Neonatal intensive care unit at a university hospital.

Patients

Twelve pre-term and term neonates (mean age: 23 days; mean body weight: 2,465 g; mean gestational age: 34 weeks; mean birth weight: 2,040 g).

Interventions

Change in body position in the sequence: supine, right lateral, prone, supine.

Measurements and results

EIT measurements were performed using the Göttingen GoeMF I system. EIT scans of regional lung ventilation showing the distribution of respired air in the chest cross-section were generated during phases of rapid tidal breathing and deep breaths. During tidal breathing, 54.5±8.3%, 55.2±10.5%, 59.9±8.4% and 54.2±8.5% of inspired air (mean values ± SD) were directed into the right lung in the supine, right lateral, prone and repeated supine postures respectively. During deep inspirations, the right lung ventilation accounted for 52.6±7.9%, 68.5±8.5%, 55.4±8.2% and 50.5±6.6% of total ventilation respectively.

Conclusion

The study identified the significant effect of breathing pattern and posture on the spatial distribution of lung ventilation in spontaneously breathing neonates. The results demonstrate that changes in regional ventilation can easily be determined by EIT and bode well for the future use of this method in paediatric intensive care.

     

Expert Consensus on the Management of Patients with Postmenopausal Osteoporosis in the Spanish Healthcare System

Introduction

The management of postmenopausal osteoporosis (PMO) in routine clinical practice differs considerably from guideline recommendations. The objective of our study was to reach a consensus on the management of PMO, considering prevention, diagnosis, treatment and follow-up, according to expert opinion in Spain.

Methods

A two-round Delphi technique was conducted, including 38 experts. The questionnaire contained 35 sections, each one including 1–10 questions (n = 308) based on a literature review and contributions from the scientific steering committee. Each question was scored by experts from the current (1 = no occurrence, 9 = occurrence in all cases), wish (1 = total rejection; 9 = wish) and prediction (1 = no occurrence at all; 9 = occurs with maximum probability) perspectives. Consensus (wish and prediction perspectives) was considered when ≥75% of experts scored 7–9 (agreement) or 1–3 (disagreement).

Results

Overall, consensus was achieved on 75% of questions. While protocols of clinical management and consultation/referral should be followed, their implementation is unlikely. Furthermore, the medical specialties currently involved in PMO management are poorly defined. PMO patients without fracture should be managed (prevention, diagnosis, treatment and follow-up) in both primary care and rheumatology settings; however, experts predicted that only treatment and follow-up will be assumed by these specialties. A multidisciplinary team should be involved in patients with fracture. No assessment tools are usually applied, and prediction indicated that they will not be used.

Conclusion

Efforts should be focused on questions with high divergence between wishes and predictions, defining actions that will improve PMO management. Collaboration between scientific societies and health authorities to address the identified opportunities of improvement is proposed.

Funding

Amgen S.A.

     

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(?) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(?) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

     

Healthcare Costs Among Adults with Type 2 Diabetes Initiating DPP-4 Inhibitors

Introduction

Oral antidiabetes medications, including dipeptidyl peptidase-4 inhibitors (DPP-4is) saxagliptin and sitagliptin, are used for the treatment of type 2 diabetes (T2D). The study objective was to compare all-cause and diabetes-related costs following initiation of saxagliptin or sitagliptin.

Methods

Patients aged ≥18 years initiating saxagliptin or sitagliptin between January 1, 2009 and January 31, 2012 in the Truven Health MarketScan Commercial and Medicare Supplemental databases were identified. Patients were required to have continuous enrollment for ≥365 days before and ≥365 days after the index date (date of the first saxagliptin or sitagliptin claim). Additionally, patients were required to have a claim with a T2D diagnosis (ICD-9-CM 250.×0, 250.×2) and no claims for a DPP-4i medication before the index date. All-cause and diabetes-related medical costs and total costs (including pharmacy costs) were captured over the 1-year follow-up period. Generalized linear models with log link and gamma distribution were fit to compare costs between the two cohorts using cost ratios, controlling for patient baseline characteristics. Recycled prediction methods were used to generate adjusted predicted costs and confidence intervals.

Results

The final sample comprised 3354 saxagliptin initiators and 26,895 sitagliptin initiators. The average age of saxagliptin and sitagliptin initiators was 57 years and just over 50% were males. After adjusting for baseline characteristics, saxagliptin patients had significantly lower average all-cause medical costs (cost ratio = 0.901, P < 0.001; predicted mean costs: $8687 vs. $9646) compared with sitagliptin patients over the 1-year follow-up. Findings were consistent for diabetes-related medical costs (cost ratio = 0.890, P < 0.001; predicted mean costs: $2180 vs. $2450). Total costs were also lower for saxagliptin initiators (cost ratio = 0.950, P = 0.002; predicted mean costs: $13,911 vs. $14,651) over the 1-year follow-up period.

Conclusion

Initiation of treatment with saxagliptin was associated with lower medical costs over 1 year compared with initiation of sitagliptin among adults with T2D.

Funding

AstraZeneca.