Early response to caplacizumab and rituximab after anaphylaxis to Octaplas plasma in a patient with thrombotic thrombocytopenic purpura.

Management of aTTP in patients who refuse or are intolerant to plasma remains challenging, but new drugs can be implemented with success. A 39-year-old woman presented to the Emergency department for bruises at the upper and lower limbs together with worsening anemia and thrombocytopenia; PLASMIC score was seven, indicative of high risk to have a thrombotic microangiopathy due to severe ADAMTS-13 deficiency: indeed, it was 1.4%. We immediately started Plasma Exchange, but after the third procedure she developed severe anaphylaxis to Octaplas plasma, so PEXs were discontinued. We proceeded to a salvage strategy with rituximab and caplacizumab that was rapidly effective to resolve symptoms and hemolysis. It has been already reported a case in which a patient developed severe reactions to fresh-frozen plasma that required discontinuation of PEX. Differently from this case, our patient was already using the less immunogenic pooled plasma units Octaplas, therefore a strategy with caplacizumab was the only available option. Moreover, rituximab is associated with a shorter time to obtain a durable remission in aTTP and a faster time (15 days) to final ADAMTS13 activity recovery >10%. To our knowledge, this is the first case of early discontinuation of caplacizumab in a patient allergic to PEX by actively monitoring ADAMTS13 activity, allowing optimization of healthcare resources during COVID-19 pandemic.

Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.

BACKGROUND: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. METHODS: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy. RESULTS: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. CONCLUSION: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Italian Real-World Analysis of a Tyrosine Kinase Inhibitor Administration as First- or Second-Line of Therapy in Patients with Chronic Myeloid Leukemia.

PURPOSE: To date, litte evidence is reported about the real-life dosage of tyrosine kinase inhibitors prescribed in Italy. The present observational retrospective study aimed to evaluate the mean daily dose of nilotinib prescribed as first- and second-line therapy among patients suffering from chronic myeloid leukemia (CML) in settings of clinical practice in Italy. PATIENTS AND METHODS: Data were obtained from the administrative databases of a sample of Italian entities. All adult patients prescribed nilotinib were included from January 2013 to December 2016 if they were using it as first-line and from January 2015 to December 2018 as second-line therapy. The mean daily dose was calculated considering the dosage between first and last nilotinib prescription date or last BCR/ABL test date. RESULTS: Among CML patients treated with nilotinib as first-line (N=87), the mean daily dose of nilotinib was 500.5 mg during a mean treatment duration of 798.9 days and of 498.54 mg considering the last determination of BCR/ABL test (mean duration of 811 days). A total of 103 CML patients were prescribed nilotinib as second-line therapy; of them, 80.6% had previously received imatinib, 17.5% dasatinib. The mean daily dose of nilotinib was found to be 566.3 mg with a mean time duration of 302.8 days, while when the last BCR/ABL test was taken into account (mean duration of 323.1 days), a mean daily dose of 565.2 mg was detected. CONCLUSION: The study reported on the real-world dosage pattern of a TKI for CML management. Our results compared with the dosage of nilotinib reported in datasheet (600 mg and 800 mg for first- and second-line, respectively) showed a trend of mean daily dose prescribed in clinical practice settings lower than the dosage currently indicated.

Impact of Guidance on the Prescription Patterns of G-CSFs for the Prevention of Febrile Neutropenia Following Anticancer Chemotherapy: A Population-Based Utilization Study in the Lazio Region.

BACKGROUND: Current guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) for patients with cancer who are at greater risk of febrile neutropenia (FN) while receiving chemotherapy. G-CSF biosimilars are available and represent a savings opportunity; however, their uptake has thus far been low. OBJECTIVE: Our objective was to evaluate prescribing patterns for G-CSFs in the prevention of chemotherapy-related FN and to evaluate the impact of regional guidance on G-CSF prescription. METHODS: We conducted an observational drug-utilization study in the Lazio region of Italy using the Electronic Therapeutic Plan Registry, which collects information on G-CSF prescriptions reimbursed by the regional health service. This registry includes information on demographics, tumour, indication for G-CSF use and previous G-CSF exposure. All therapeutic plans (TPs) registered from 1 July 2015 to 30 June 2016 were selected. A pharmaceutical policy intervention was implemented in November 2015. We evaluated temporal trends regarding G-CSF substances and compared the frequency of TPs for each G-CSF substance during the pre- and post-intervention periods. RESULTS: A total of 7082 TPs were eligible for the analysis, corresponding to 6592 patients. The frequency of TPs prescribed after the intervention indicated a significant increase in the use of a filgrastim biosimilar (% difference: 14.4; p < 0.001) and significant decreases in the use of lenograstim (% difference: -6.0; p < 0.001) and pegfilgrastim (% difference: -7.8; p < 0.001). The temporal trends analysis showed an increase in TPs using a filgrastim biosimilar (from 34.4% in July 2015 to 49.8% in June 2016; p < 0.0001) and a decrease in TPs using lenograstim and pegfilgrastim. CONCLUSIONS: This study shows it is possible to change attitudes towards the prescription of less expensive G-CSFs in the FN setting when the prescriber's decision-making processes are supported by evidence that includes both regulatory and clinical information and the analysis of clinical practice data.

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy.

OBJECTIVES: To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice. DESIGN: Population-based observational cohort study. SETTING: All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014. PARTICIPANTS: Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively. INTERVENTIONS: ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period. OUTCOME MEASURES: Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression. RESULTS: We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting. CONCLUSIONS: In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.