Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

Background Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. Methods Data from two retrospective cohorts of ‘real-life’ use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. Results Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71–2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50–3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. Conclusions We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Background and importance Polypharmacy and potentially inappropriate medications (PIMs) are known problems in elderly patients, but their prevalence in cancer and end-of-life settings are less clear. Also, the number of specific criteria to assist clinicians in this setting is limited. Aim and objectives To analyse the prevalence of polypharmacy and PIMs in elderly oncohaematological patients referred for palliative care. Material and methods A retrospective observational study was conducted in a third level hospital. Oncohaematological patients aged 65 or older referred to palliative care between 1 April 2020 and 30 June 2020 were included. Gender, age, primary malignancy, ECOG performance score, comorbidities and chronic medications were collected. Survival was screened during a follow-up period of 3 months after first contact with the palliative care team. Demographic and clinical data were collected from the patient electronic medical records. Polypharmacy was defined as the use of five or more chronic drugs. PIMs were screened using the STOPPFrail criteria. Results 62 patients were included, 39 men (63%), median age 78.5 years (range 65-94). 51 (82%) were oncological patients, 11 (18%) had a haematological malignancy and 53 (85%) had an ECOG !3. Mean number of comorbidities per patient was 2.7±1.8 and mean number of chronic drugs was 7.4±3.5. Polypharmacy was present in 49 (79%) patients. 85 PIMs were detected. At least one PIM was detected in 50 (80%) patients (mean 1.3±0.9). The most frequent STOPPFrail criteria were B1 (lipid lowering therapies) (n=21), E1 (proton pump inhibitors at full therapeutic dose) (n=17), G1 (calcium supplementation) (n=11), A2 (drugs without clear clinical indication) (n=8) and I1 (antidiabetic oral agents) (n=8). Only 9 patients (14.5%) remained alive at the end of the follow-up period. Conclusion and relevance The outcomes confirmed a high prevalence of polypharmacy and PIMs in elderly oncohaematological patients referred to palliative care. The STOPPFrail criteria might be useful in the detection of futile drugs eligible for deprescription in this population.

Introduction Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene is gaining importance to be able to predict fluoropyrimidine-associated toxicity. The aim of this project was to describe the frequency of the DPYD variants DPYD*2A (rs3918290); c.1679T>G (rs55886062); c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in the Spanish oncological patients. Material and methods Cross-sectional and multicentric study (PhotoDPYD study) conducted in hospitals located in Spain designed to register the frequency of the most relevant DPYD genetic variants in oncological patients. All oncological patients with DPYD genotype were recruited in the participant hospitals. The measures determined where the presence or not of the 4 DPYD previously described variants. Results Blood samples from 8054 patients with cancer from 40 different hospitals were used to determine the prevalence of the 4 variants located in the DPYD gene. The frequency of carriers of one defective DPYD variant was 4.9%. The most frequently identified variant was c.1129-5923C>G (rs75017182) (HapB3), in 2.9%, followed by c.2846A>T (rs67376798) in 1.4%, c.1905 + 1G>A (rs3918290, DPYD*2A) in 0.7% and c.1679T>G (rs55886062) in 0.2% of the patients. Only 7 patients (0.08%) were carrying the c.1129-5923C>G (rs75017182) (HapB3) variant, 3 (0.04%) the c.1905 + 1G>A (rs3918290, DPYD*2A) and one (0.01%) the DPYD c.2846A>T (rs67376798, p.D949V) variant in homozygosis. Moreover, 0.07% were compound heterozygous patients, 3 carrying the DPYD variants DPYD*2A + c.2846A>T, 2 the DPYD c.1129-5923C>G + c.2846A>T and one the DPYD*2A + c.1129-5923C>G variants. Conclusions Our results demonstrate the relatively high frequency of DPYD genetic variants in the Spanish patient with cancer population, which highlights the relevance of their determination before initiating a fluoropirimidine-containing regimen.