Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with infliximab reference product in patients with rheumatoid arthritis.

BACKGROUND: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

Pharmacokinetic Similarity of ABP 710, a Proposed Biosimilar to Infliximab: Results From a Randomized, Single-Blind, Single-Dose, Parallel-Group Study in Healthy Subjects.

This was a randomized, single-blind, single-dose, 3-arm parallel-group study. Healthy subjects were randomized to receive ABP 710 (n = 50) or infliximab reference product (RP) sourced from the United States (infliximab US; n = 50) or the European Union (infliximab EU; n = 50) 5 mg/kg intravenously over 2 hours. The primary endpoint was area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf ) for the comparison of ABP 710 to infliximab US and infliximab EU. Secondary endpoints included safety, tolerability, and immunogenicity. AUCinf was similar across the 3 groups, showing similarity of ABP 710 to infliximab RP as well as similarity of infliximab US with infliximab EU. Geometric mean ratio of AUCinf was 0.89 between ABP 710 and infliximab US, 1.00 between ABP 710 and infliximab EU, and 1.11 between infliximab US and infliximab EU. All 90% confidence intervals of the geometric mean ratios were fully contained within the prespecified standard pharmacokinetic equivalence criteria range of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and reported for 83.7%, 86.0%, and 83.7% of subjects in the ABP 710, infliximab US, and infliximab EU treatment groups, respectively; incidence of antidrug antibody rates observed across the 3 groups were similar. Results of this study demonstrated pharmacokinetic similarity of ABP 710 with infliximab RP following a single 5-mg/kg intravenous injection. The safety and tolerability of ABP 710 and infliximab RP were comparable. These results add to the totality of evidence providing further support that the proposed biosimilar ABP 710 is similar to infliximab RP. (Trial ID: ACTRN12614000903684.).

A Review of the Totality of Evidence Supporting the Development of the First Adalimumab Biosimilar ABP 501.

ABP 501 [United States: AMJEVITA™ (adalimumab-atto); European Union: AMGEVITA® (adalimumab)] is the first approved biosimilar to adalimumab [reference product (RP)], a monoclonal antibody (mAb) targeting tumor necrosis factor-alfa (TNF-α). ABP 501 has received approval for use in indications that adalimumab RP is approved for, except those protected by regulatory exclusivity. A systematic step-wise totality of evidence (TOE) approach formed the basis of approval of ABP 501; this involved methodical accumulation of scientifically robust comparative data supporting similarity in analytical, preclinical, and clinical [pharmacokinetics (PK)], efficacy, safety and immunogenicity) evaluations. As a foundational first step, comprehensive analytical assessments demonstrated that ABP 501 is structurally and functionally similar to adalimumab RP in critical quality attributes. Preclinical assessments confirmed similar activity in assessing mechanisms of action and toxicology. Clinical evaluation included a phase 1 PK equivalence study in healthy subjects and two comparative phase 3 studies that evaluated ABP 501 and adalimumab RP in two sensitive patient populations, plaque psoriasis (PsO) and rheumatoid arthritis (RA). The PK profiles of ABP 501 and adalimumab RP were similar in healthy subjects as well as patients with PsO and RA. The pivotal phase 3 study in patients with PsO demonstrated that ABP 501 was clinically similar to adalimumab RP in terms of efficacy, safety and immunogenicity in both the primary and transition phases. The pivotal phase 3 study in patients with RA also established clinical similarity between ABP 501 and adalimumab RP; an open-label extension of this study demonstrated sustained efficacy over an additional 72 weeks, with no new safety or immunogenicity concerns with ABP 501 treatment. Overall, the TOE supported the conclusion that ABP 501 is highly similar to adalimumab RP and provided scientific justification for extrapolation to all the approved indications of adalimumab RP not protected by exclusivities.Funding: Amgen Inc.

Critical role of nutrition in improving quality of care: an interdisciplinary call to action to address adult hospital malnutrition.

The current era of health care delivery, with its focus on providing high-quality, affordable care, presents many challenges to hospital-based health professionals. The prevention and treatment of hospital malnutrition offers a tremendous opportunity to optimize the overall quality of patient care, improve clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go unrecognized and untreated in many hospitalized patients. This article represents a call to action from the interdisciplinary Alliance to Advance Patient Nutrition to highlight the critical role of nutrition intervention in clinical care and suggest practical ways for prompt diagosis and treatment of malnourished patients and those at risk for malnutrition. We underscore the importance of an interdisciplinary approach to addressing malnutrition both in the hospital and in the acute post-hospital phase. It is well recognized that malnutrition is associated with adverse clinical outcomes. Although data vary across studies, available evidence shows early nutrition intervention can reduce complication rates, length of hospital stay, re-admission rates, mortality, and cost of care. The key is to identify patients systematically who are malnourished or at risk and to promptly intervene. We present a novel care model to drive improvement, emphasizing the following six principles: (1) create an institutional culture where all stakeholders value nutrition; (2) redefine clinicians' roles to include nutrition care; (3) recognize and diagnose all malnourished patients and those at risk; (4) rapidly implement comprehensive nutrition interventions and continued monitoring; (5) communicate nutrition care plans; and (6) develop a comprehensive discharge nutrition care and education plan.

Critical role of nutrition in improving quality of care: an interdisciplinary call to action to address adult hospital malnutrition.

The current era of health care delivery, with its focus on providing high-quality, affordable care, presents many challenges to hospital-based health professionals. The prevention and treatment of hospital malnutrition offers a tremendous opportunity to optimize the overall quality of patient care, improve clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go unrecognized and untreated in many hospitalized patients. This article represents a call to action from the interdisciplinary Alliance to Advance Patient Nutrition to highlight the critical role of nutrition intervention in clinical care and to suggest practical ways to promptly diagnose and treat malnourished patients and those at risk for malnutrition. We underscore the importance of an interdisciplinary approach to addressing malnutrition both in the hospital and in the acute post-hospital phase. It is well recognized that malnutrition is associated with adverse clinical outcomes. Although data vary across studies, available evidence shows that early nutrition intervention can reduce complication rates, length of hospital stay, readmission rates, mortality, and cost of care. The key is to systematically identify patients who are malnourished or at risk and to promptly intervene. We present a novel care model to drive improvement, emphasizing the following six principles: (1) create an institutional culture where all stakeholders value nutrition; (2) redefine clinicians' roles to include nutrition care; (3) recognize and diagnose all malnourished patients and those at risk; (4) rapidly implement comprehensive nutrition interventions and continued monitoring; (5) communicate nutrition care plans; and (6) develop a comprehensive discharge nutrition care and education plan.

Critical role of nutrition in improving quality of care: an interdisciplinary call to action to address adult hospital malnutrition.

The current era of healthcare delivery, with its focus on providing high-quality, affordable care, presents many challenges to hospital-based health professionals. The prevention and treatment of hospital malnutrition offer a tremendous opportunity to optimize the overall quality of patient care, improve clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go unrecognized and untreated in many hospitalized patients. This article represents a call to action from the interdisciplinary Alliance to Advance Patient Nutrition to highlight the critical role of nutrition intervention in clinical care and to suggest practical ways to promptly diagnose and treat malnourished patients and those at risk for malnutrition. We underscore the importance of an interdisciplinary approach to addressing malnutrition both in the hospital and in the acute posthospital phase. It is well recognized that malnutrition is associated with adverse clinical outcomes. Although data vary across studies, available evidence shows that early nutrition intervention can reduce complication rates, length of hospital stay, readmission rates, mortality, and cost of care. The key is to systematically identify patients who are malnourished or at risk and to promptly intervene. We present a novel care model to drive improvement, emphasizing the following 6 principles: (1) create an institutional culture where all stakeholders value nutrition, (2) redefine clinicians' roles to include nutrition care, (3) recognize and diagnose all malnourished patients and those at risk, (4) rapidly implement comprehensive nutrition interventions and continued monitoring, (5) communicate nutrition care plans, and (6) develop a comprehensive discharge nutrition care and education plan.

Providing patients web-based data to inform physician choice: if you build it, will they come?

BACKGROUND: Despite growing emphasis on public reporting of health care quality data, available data are often ignored. OBJECTIVE: To evaluate the usefulness of web-based physician-level data for patients choosing a new primary care physician (PCP). DESIGN: Patients seeking a new PCP (n = 2225) were invited to view web-based information including PCP credentials, personal characteristics, office location and hours, and patient experience scores. Patient experience scores included validated measures of interpersonal quality, appointment access, care coordination, health promotion, and patient recommendations of the PCP. After viewing the website, participants indicated their preferred PCP and completed a study questionnaire. RESULTS: Of the invited participants, 17% visited the website (n = 382). Patient experience scores were cited most frequently as important to physician choice (51%). Among these measures, patients' highest priorities were interpersonal quality (37%) and patient recommendations of the PCP (41%). For patients citing these priorities, the odds of choosing a highly scored physician after viewing the data was nearly 10 times that of choosing such a physician by chance (odds ratio (OR) = 9.52 and 9.71, respectively). CONCLUSIONS: Targeting patients known to be making a health care decision appears to promote the use of performance data. Patients particularly valued data concerning other patients' experiences and, after viewing the data, made choices well-aligned with their priorities.

Nutrition and performance in children.

PURPOSE OF REVIEW: Malnutrition in late infancy and childhood remains a significant public health issue in developing nations as well as for those in transition to an industrialized economy. In addition, in these settings and particularly in developed nations, overweight is becoming a very serious threat to both the immediate and the long-term health of children. In this review, we present recent studies that have examined relationships between childhood undernutrition and three general areas of performance: physical activity, cognition and behavior. RECENT FINDINGS: Malnourished children have been shown to have decreased physical activity and endurance, and poorer cognitive function and school performance. Multiple single micronutrient deficiencies, including vitamin B12, thiamin, niacin, zinc and iron, have been associated with poorer cognitive performance. Behavioral problems, including attention deficits, have also been associated with food insufficiency and malnutrition. SUMMARY: The effects of impaired nutritional status during childhood may have long-standing consequences for the health and performance of children during their adult years.

Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis.

OBJECTIVES: We evaluated the response to infliximab in pediatric patients with ulcerative colitis (UC) and their long-term follow-up. We expanded our previous study of 14 patients and furthermore evaluated the success of weaning patients from infliximab. PATIENTS AND METHODS: We reviewed the charts of 27 pediatric patients with UC who were treated with infliximab instead of undergoing a colectomy. Patients with new-onset UC refractory to intravenous steroids for 5 to 10 days and patients with non-steroid-dependent UC with an acute exacerbation were classified as acutely ill (n = 16); patients with chronic steroid-dependent UC were classified as chronically ill (n = 11). The Lichtiger Colitis Activity Index (LCAI) was measured for all patients at baseline and at 1 and 2 months after treatment with infliximab was initiated. Patients were regarded as successfully treated if they remained off steroids and avoided colectomy. RESULTS: The acutely ill group had a mean LCAI score of 11.4 at induction and 0.3 after 2 months. The chronically ill group had a mean LCAI score of 11.2 at induction and 5.5 after 2 months. Treatment with infliximab was successful in 75% of acutely ill patients and in 27% of chronically ill patients. Infliximab was discontinued in 80% of successfully treated patients (83% of acutely ill, 67% of chronically ill). These patients had an average of 10 infusions and a mean follow-up time of 10 months from their last infliximab infusion. CONCLUSIONS: Our results suggest that infliximab is more effective in acutely ill UC patients than in patients with chronic steroid-dependent UC. In addition, some patients treated with infliximab can be weaned from infliximab and maintain remission.

Evaluating patients' experiences with individual physicians: a randomized trial of mail, internet, and interactive voice response telephone administration of surveys.

BACKGROUND: There is increasing interest in measuring patients' experiences with individual physicians, and empirical evidence supports this area of measurement. However, the high cost of data collection remains a significant barrier. Survey modes with the potential to lower costs, such as Internet and interactive voice response (IVR) telephone, are attractive alternatives to mail, but their comparative response rates and data quality have not been tested. METHODS: We randomly assigned adult patients from the panels of 62 primary care physicians in California to complete a brief, validated patient questionnaire by mail, Internet (web), or IVR. After 2 invitations, web and IVR nonrespondents were mailed a paper copy of the survey ("crossover" to mail). We analyzed and compared (n = 9126) the response rates, respondent characteristics, substantive responses, and costs by mode (mail, web and IVR) and evaluated the impact of "crossover" respondents. RESULTS: Response rates were higher by mail (50.8%) than web (18.4%) or IVR (34.7%), but after crossover mailings, response rates in each arm were approximately 50%. Mail and web produced identical scores for individual physicians, but IVR scores were significantly lower even after adjusting for respondent characteristics. There were no significant physician-mode interactions, indicating that statistical adjustment for mode resolves the IVR effect. Web and IVR costs were higher than mail. CONCLUSIONS: The equivalence of individual physician results in mail and web modes is noteworthy, as is evidence that IVR results are comparable after adjustment for mode. However, the higher overall cost of web and IVR, as the result of the need for mailings to support these modes, suggests that they do not presently solve cost concerns related to obtaining physician-specific information from patients.