BACKGROUND: Patients with severe asthma not meeting the strict trial eligibility criteria for mepolizumab are now routinely treated with this biological in clinical practice, but it remains unclear... Show moreBACKGROUND: Patients with severe asthma not meeting the strict trial eligibility criteria for mepolizumab are now routinely treated with this biological in clinical practice, but it remains unclear whether these ineligible patients respond differently to mepolizumab treatment.OBJECTIVE: This study investigated the extent and reasons for trial ineligibility of real-life, mepolizumab-treated patients with severe asthma and compared the characteristics of these patients with trial populations. Subsequently, therapeutic response in ineligible patients was assessed on the basis of oral corticosteroid (OCS) reduction.METHODS: Trial eligibility, population differences, and therapeutic response were assessed using the baseline characteristics of mepolizumab-receiving patients with severe asthma treated in the Amsterdam University Medical Centres and OCS dose at 6 months for OCS-dependent patients extracted from patients' electronic health records. Eligibility criteria and population characteristics from trials investigating mepolizumab were extracted from their original publications.RESULTS: A total of 82.4% of 119 mepolizumab-receiving, reallife patients with severe asthma were ineligible for trial inclusion, wherein 42.9% and 39.5% were excluded on the basis of inclusion and exclusion criteria, respectively. The clinical care population was older, more often male and demonstrating a better lung function under lower OCS maintenance dosages in comparison with trial populations. A total of 50% of 66 ineligible, OCS-dependent mepolizumab-treated patients were able to reduce their maintenance OCS dosage to <= 5 mg prednisone/day.CONCLUSIONS: A large proportion of the real-life, mepolizumab-treated population with severe asthma would be excluded from trial participation, and significant differences in population characteristics exist. Regardless, a large fraction of ineligible patients in clinical care can reduce maintenance OCS dosage under mepolizumab therapy. (C) 2020 American Academy of Allergy, Asthma & Immunology. Show less
Zazuli, Z.; Kos, R.; Veltman, J.D.; Uyterlinde, W.; Longo, C.; Baas, P.; ... ; Zee, A.H.M. van der 2020
Aim Antineoplastic effect of cisplatin, the first line treatment in non-small cell lung cancer (NSCLC), is hindered by its nephrotoxicity and myelotoxicity. Both low-dose and high-dose regimens are... Show moreAim Antineoplastic effect of cisplatin, the first line treatment in non-small cell lung cancer (NSCLC), is hindered by its nephrotoxicity and myelotoxicity. Both low-dose and high-dose regimens are used in the management of NSCLC. The aim of this study is to assess the risk on myelotoxicity and nephrotoxicity from the daily low-dose cisplatin (DLD) treatment as compared to cyclic high-dose cisplatin (CHD). Methods A retrospective cohort study was conducted. NSCLC patients treated with cisplatin between 2011 and 2018 in the Amsterdam UMC or Antoni van Leeuwenhoek cancer hospital were studied. Myelotoxicity and nephrotoxicity were defined based on common terminology criteria (CTCAE v4.03) and categorized as >= grade 1 and >= grade 2. Modified Poisson regression and Cox proportional hazards model were used to estimate relative risks and cumulative hazard respectively. Results Of the 115 NSCLC patients receiving DLD (N=62) and CHD (N=53), 60% had >= grade 1 anemia, 33.9% leukopenia, 31.3% neutropenia, 27.8% thrombocytopenia, 32.2% acute nephrotoxicity with combined definition (Cr-electrolyte nephrotoxicity), and 58.3% chronic nephrotoxicity. The DLD group was older, had an earlier cancer stage, had more comorbidities, and had higher baseline albumin levels. In the DLD group less >= grade 2 toxicities were reported compared to the CHD group except for Cr-electrolyte nephrotoxicity. However, there was a stronger association in the DLD group with >= grade 1 leukopenia, thrombocytopenia, and Cr-electrolyte nephrotoxicity. The DLD group developed significantly more >= grade 1 leukopenia [adjusted relative risk (adjRR)=1.83, 95% CI 1.02-3.27], thrombocytopenia (adjRR=3.43, 95% CI 1.64-7.15), and >= grade 2 Cr-electrolyte nephrotoxicity (adjRR=3.02, 95% CI 1.20-7.56). The DLD group had a lower adjusted cumulative hazard for developing >= grade 2 myelotoxicity and chronic nephrotoxicity but not for Cr-electrolyte nephrotoxicity [adjusted hazard ratio (adjHR)=3.90, 95% CI 1.35-11.23]. In contrast, DLD showed protective effect to >= grade 2 nephrotoxicity when definition was restricted to the traditional creatinine-based definition (adjRR=0.07, 95% CI 0.01-0.86; adjHR=0.05, 95% CI 0.01-0.56). Conclusions Overall, the DLD regimen was safer than the CHD regimen when assessing the risk of >= grade 2 myelotoxicity and nephrotoxicity. However, this might not be the case in patients with a higher risk of electrolyte abnormalities. Show less
