The safety and clinical effectiveness of rapid infusion with CT-P10 in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non-interventional post-authorization safety study in Europe.

Rapid infusion (RI) of the rituximab biosimilar CT-P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT-P10 and reference rituximab are known to be frequently administered using a RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT-P10 in patients with NHL and CLL are limited. Hence, this study collected real-world safety and effectiveness data on RI-CT-P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion-related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%-15%; n = 20/196) of patients experienced an infusion-related reaction (IRR) on day 1-2 post-index, which was not significantly different (p = 0.45) to the IRR rate for rituximab described in a previous meta-analysis (8.8%). During the observation period, 2% of patients experienced grade 3-5 IRRs and 85% (n = 166) experienced an adverse event (non-IRR). The most common reason for discontinuation of first-line CT-P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT-P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real-world study demonstrate that the safety and effectiveness profile of RI-CT-P10 is similar to RI of reference rituximab and therefore support the current use of RI-CT-P10 in patients with NHL and CLL.

A survey of global biosimilar implementation practice conducted by the International Society of Oncology Pharmacy Practitioners.

Background: The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilars Task Force was charged to develop educational activities and resources to assist members when implementing biosimilar medicines into their local practice. To facilitate the process, the task force conducted a survey in order to understand biosimilar implementation practice by ISOPP members across the world and the challenges that oncology pharmacists face when adopting biosimilars into their clinical practice. Methods: A cross-sectional survey was conducted between 20 April 2019 and 27 May 2019. Members of ISOPP and a number of national oncology pharmacy groups were invited to complete the survey. The survey contained 29 items and consisted of three sections: respondents' demographics, respondents' institutional practice relating to biosimilar implementation and post implementation practice at the respondents' institutions. Descriptive statistics were utilized to analyze the survey results. Results: A total of 265 ISOPP members were surveyed, with 50 members providing a response (response rate = 19%). In addition, 40 nonmembers participated in the survey, bringing the total to 90 respondents. The most common factors that influence the decision to implement use of a biosimilar as reported by respondents are medication costs/pricing (92%), available clinical data (73%), and product availability (63%). Respondents also commented on the barriers to biosimilar implementation at their institutions, which included a reluctance of prescribers to use biosimilars (due to the lack of familiarity or perceived inferiority), a reluctance to switch established patients from an originator to a biosimilar and the preferences of insurance companies or funding bodies. Conclusion: The results of this survey reinforce the need for greater education and training for health care professionals in the use of biosimilars, the importance of sharing good practice, and a need for standardization.

International Society of Oncology Pharmacy Practitioners global position on the use of biosimilars in cancer treatment and supportive care.

With the development of innovative cancer treatments over recent decades, the cost of cancer care has risen exponentially, limiting patient access to patented originator biotherapeutics in many countries. The introduction of biosimilars to the market has created new opportunities as well the need for changes in practice within healthcare institutions. A 'biosimilar' is a biotherapeutic product which is highly similar in terms of quality, safety and efficacy to an already licensed originator product. Although biosimilars lack clinically meaningful differences in therapeutic activity as compared to the originator product, these complex biological molecules are not considered identical chemical copies, unlike generics, and minor differences in molecular structure and inactive compounds may exist. A thorough understanding of these differences and their clinical implications is necessary for optimising medicines-use practices involving biosimilars. This position statement, developed by the International Society of Oncology Pharmacy Practitioners Biosimilars Taskforce, aims to provide the global oncology pharmacy community with guidance to support decisions around biosimilar use. The 11 statements cover the regulation and evaluation of biosimilars, practical issues around local implementation, the education of healthcare staff and patients, and the requirement for ongoing pharmacovigilance and outcome monitoring.

Can doctors identify older patients at risk of medication harm following hospital discharge? A multicentre prospective study in the UK.

AIMS: Medication-related harm (MRH) is common in older adults following hospital discharge. In resource-limited health systems, interventions to reduce this risk can be targeted at high-risk patients. This study aims to determine whether (1) doctors can predict which older patients will experience MRH requiring healthcare following hospital discharge, (2) clinical experience and confidence in prediction influence the accuracy of the prediction. METHODS: This was a multicentre observational prospective study involving five teaching hospitals in England between September 2013 and November 2015. Doctors discharging patients (aged ≥65 years) from medical wards predicted the likelihood of their patient experiencing MRH requiring healthcare (hospital readmission or community healthcare) in the initial 8-week period post-discharge. Patients were followed up by senior pharmacists to determine MRH occurrence. RESULTS: Data of 1066 patients (83%) with completed predictions and follow-up, out of 1280 recruited patients, were analysed. Patients had a median age of 82 years (65-103 years), and 58% were female. Most predictions (85%) were made by junior doctors with less than 5 years' clinical experience. There was no relationship between doctors' predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective of years of clinical experience. Doctors' predictions were more likely to be accurate when they reported higher confidence in their prediction, especially in predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P < 0.001). CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to predict MRH in older adults post-discharge.

Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

Protocol for a Prospective (P) study to develop a model to stratify the risk (RI) of medication (M) related harm in hospitalized elderly (E) patients in the UK (The PRIME study).

BACKGROUND: Medication related harm (MRH) is a common cause of morbidity and hospital admission in the elderly, and has significant cost implications for both primary and secondary healthcare resources. The development of risk prediction models has become an increasingly common phenomenon in medicine and can be useful to guide objective clinical decision making, resource allocation and intervention. There are no risk prediction models that are widely used in clinical practice to identify elderly patients at high risk of MRH following hospital discharge. The aim of this study is to develop a risk prediction model (RPM) to identify elderly patients at high risk of MRH upon discharge from hospital, and to compare this with routine clinical judgment. METHODS/DESIGN: This is a multi-centre, prospective observational study following a cohort of patients for 8 weeks after hospital discharge. Data collection including patient characteristics, medication use, social factors and frailty will take place prior to patient discharge and then the patient will be followed up in the community over the next 8 weeks to determine if they have experienced MRH. Research pharmacists will determine whether patients have experienced MRH by prospectively reviewing records for unplanned emergency department attendance, hospital readmission and GP consultation related to MRH. Research pharmacists will also telephone patients directly to determine self-reported MRH, which patients may not have sought further medical attention for. The data collected will inform the development of a RPM which will be externally validated in a follow-up study. DISCUSSION: There are no RPMs that are used in clinical practice to help stratify elderly patients at high risk of MRH in the community following hospital discharge, despite this being a significant public health problem. This study plans to develop a clinically useful RPM that is better than routine clinical judgment. As this is a multi-centre study involving clinical settings that serve elderly people of heterogeneous sociodemographic background, it is anticipated that this RPM will be generalizable.

Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-cell lymphoma: An observational study in Europe.

The rituximab biosimilar CT-P10 is approved for the treatment of non-Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT-P10 and reference rituximab. However, real-world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real-world data relating to the effectiveness and safety of CT-P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression-free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12-, 18-, and 30 months postindex (initiation of CT-P10) was 86% (82.4%-89.4%), 81% (76.9%-84.9%), and 76% (71.2%-80.1%), respectively. The PFS rate (percent, [95% CI]) at 12-, 18-, and 30 months postindex was 78% (74.2%-82.5%), 72% (67.9%-76.9%), and 67% (61.9%-71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT-P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real-world data on the safety and effectiveness profile of CT-P10 for DLBCL treatment and supports the adoption of CT-P10 for the treatment of DLBCL.

Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool.

OBJECTIVES: To develop and validate a tool to predict the risk of an older adult experiencing medication-related harm (MRH) requiring healthcare use following hospital discharge. DESIGN, SETTING, PARTICIPANTS: Multicentre, prospective cohort study recruiting older adults (≥65 years) discharged from five UK teaching hospitals between 2013 and 2015. PRIMARY OUTCOME MEASURE: Participants were followed up for 8 weeks in the community by senior pharmacists to identify MRH (adverse drug reactions, harm from non-adherence, harm from medication error). Three data sources provided MRH and healthcare use information: hospital readmissions, primary care use, participant telephone interview. Candidate variables for prognostic modelling were selected using two systematic reviews, the views of patients with MRH and an expert panel of clinicians. Multivariable logistic regression with backward elimination, based on the Akaike Information Criterion, was used to develop the PRIME tool. The tool was internally validated. RESULTS: 1116 out of 1280 recruited participants completed follow-up (87%). Uncertain MRH cases ('possible' and 'probable') were excluded, leaving a tool derivation cohort of 818. 119 (15%) participants experienced 'definite' MRH requiring healthcare use and 699 participants did not. Modelling resulted in a prediction tool with eight variables measured at hospital discharge: age, gender, antiplatelet drug, sodium level, antidiabetic drug, past adverse drug reaction, number of medicines, living alone. The tool's discrimination C-statistic was 0.69 (0.66 after validation) and showed good calibration. Decision curve analysis demonstrated the potential value of the tool to guide clinical decision making compared with alternative approaches. CONCLUSIONS: The PRIME tool could be used to identify older patients at high risk of MRH requiring healthcare use following hospital discharge. Prior to clinical use we recommend the tool's evaluation in other settings.