11. Mixed results with baricitinib in biological-resistant adult-onset Still's disease and undifferentiated systemic autoinflammatory diseaseMark Kačar, John Fitton, Andrew K Gough, Maya H Buch, Dennis McGonagle, Sinisa Savic, 2020, original scientific article Abstract: This clinical case series describes our experience with the use of Janus kinase 1/2 inhibitor baricitinib in two patients suffering from refractory adult-onset Still's disease (AOSD) as well as in one case suffering from AOSD-like autoinflammatory disease in the context of myelodysplastic syndrome. All patients suffered from disease nonresponsive to conventional Disease-modifying antirheumatic drugs (DMARDs) as well as biological therapies including interleukin (IL)-1 and IL-6 blockade, relying instead on high daily doses of prednisolone. We also report the first case of Pneumocystis jirovecii infection following baricitinib use.
Keywords: adult onset Still's disease -- drug therapy, ankylosing spondylitis, arthritis, antirheumatic agents, undifferentiated systemic autoinflammatory disease, disease-modifying antirheumatic drugs
Published in DiRROS: 08.04.2021; Views: 1305; Downloads: 842
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12. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : final analysis of the GioTag studyMaximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Angela Märten, Tanja Čufer, 2020, original scientific article Abstract: Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment >/=10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.
Keywords: non-small cell lung carcinoma -- therapy, drug therapy, afatinib, osimertinib, GioTag study
Published in DiRROS: 18.11.2020; Views: 1454; Downloads: 1224
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13. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling : a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials2019, original scientific article Abstract: Background: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37,298 (93%) of 40,070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28.0% vs 31.4%; RR 0.86, 95% CI 0.82-0.89; p<0.0001). 10-year breast cancer mortality was similarly reduced (18.9% vs 21.3%; RR 0.87, 95% CI 0.83-0.92; p<0.0001), as was all-cause mortality (22.1% vs 24.8%; RR 0.87, 95% CI 0.83-0.91; p<0.0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4.1% vs 4.6%; RR 0.88, 95% CI 0.78-0.99; p=0.034). Recurrence reductions were similar in the seven trials (n=10,004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24.0% vs 28.3%; RR 0.83, 95% CI 0.76-0.91; p<0.0001), in the six trials (n=11,028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28.1% vs 31.3%; RR 0.87, 95% CI 0.80-0.94; p=0.0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30.4% vs 35.0%; RR 0.82, 95% CI 0.74-0.90; p<0.0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0.0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation: Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.
Keywords: breast neoplasms, women, drug therapy, clinical protocols, meta-analysis, breast cancer, chemotherapy, treatment schedule, randomized trials
Published in DiRROS: 22.10.2020; Views: 1287; Downloads: 1089
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14. ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy"Sinthia Bosnic-Anticevitch, Elisio Costa, Enrica Menditto, Olga Lourenço, Ettore Novellino, Slawomir Bialek, Vitalis Briedis, Roland Buonaiuto, Henry Chrystyn, Biljana Cvetkovski, Mihaela Zidarn, 2019, review article Abstract: Pharmacists are trusted health professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact of allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The ARIA-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses) and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of AR. However, the ARIA-pharmacy ICP should be adapted to local health care environments/situations as regional (national) differences exist in pharmacy care.
Keywords: asthma -- guideline, allergic rhinitis -- Guideline, pharmacists, drug therapy, nonprescription drugs, critical pathways, allergic diseases
Published in DiRROS: 09.10.2020; Views: 1266; Downloads: 329
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15. Position of an international panel of lung cancer experts on the decision for expansion of approval for pembrolizumab in advanced non-small-cell lung cancer with a PD-L1 expression level of >= 1 by the USA Food and Drug AdministrationGiannis Mountzios, J. Remon, Silvia Novello, N. Blais, R. Califano, Tanja Čufer, Anne-Marie C. Dingemans, S. V. Liu, N. Peled, N. A. Pennell, 2019, short scientific article Keywords: non-small cell lung carcinoma, drug therapy, KEYNOTE-024 trial, pemrolizumab, treatment
Published in DiRROS: 21.09.2020; Views: 1233; Downloads: 818
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16. Absence of adverse effects of tiotropium/ olodaterol compared with the monocomponents on long-term heart rate and blood pressure in patients with moderate-to-very-severe COPDStefan Andreas, Lorcan Mcgarvey, Ulrich Bothner, Matthias Trampisch, Alberto De La Hoz, Matjaž Fležar, Roland Buhl, Peter Alter, 2020, original scientific article Abstract: Introduction: Long-acting [beta]2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are established maintenance bronchodilator treatments for chronic obstructive pulmonary disease (COPD) with the potential to increase heart rate (HR) and impact blood pressure (BP). While previous studies indicate that HR and BP are not negatively influenced by tiotropium or olodaterol monotherapy, the effect of tiotropium/olodaterol has not been evaluated. We report a post hoc analysis of the effect of dual bronchodilation with tiotropium/olodaterol versus monocomponents on HR and BP in patients with moderate-to-very-severe COPD included in the large TONADO© study. Methods: The TONADO© trials (1237.5 [NCT01431274] and 1237.6 [NCT01431287]) were two replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials that compared tiotropium/olodaterol (5/5 [micro]g and 2.5/5 [micro]g) with tiotropium (5 [micro]g and 2.5 [micro]g) and olodaterol (5 [micro]g) in patients with moderate-to-very-severe COPD. Patients with cardiovascular comorbidities were included. Changes in HR and systolic/diastolic BP were measured before and after dosing with the study medication at each visit (baseline, Week 12, Week 24 and Week 52). Results: Overall, 3,100 patients were included in this analysis. Over 52 weeks, small changes from baseline in mean HR (<2 beats per minute [bpm]) and small changes from pre- to post-dose (<1 bpm) were evident at different time points. There was a non-significant increase from baseline in mean diastolic and systolic BP (<2 mmHg) observed over 52 weeks of treatment. The short-term (1 hour pre- to 1 hour post-dose) mean changes in systolic and diastolic BP over 52 weeks in the tiotropium/olodaterol 5/5 [micro]g group were comparable with those observed for the monocomponents at all time points. Conclusion: There were no differences in HR or BP among patients on tiotropium/olodaterol when compared with monocomponents. This supports the already demonstrated cardiovascular safety profile of tiotropium/olodaterol as long-acting maintenance bronchodilator treatment for COPD, including patients with cardiovascular comorbidities.
Keywords: pulmonary disease, chronic obstructive -- drug therapy, heart rate, blood pressure, tiotropium, olodaterol
Published in DiRROS: 21.09.2020; Views: 1419; Downloads: 941
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17. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : updated analysis of the observational GioTag studyMaximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Lara Wang, Angela Märten, Tanja Čufer, 2019, original scientific article Abstract: Aims: Overall survival (OS) and updated time to treatment failure (TTF) analysis of patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer who received sequential afatinib/osimertinib in the real-world GioTag study. Patients & methods: Patients had T790M-positive disease following first-line afatinib and received osimertinib treatment (n = 203). Primary outcome was TTF. The OS analysis was exploratory. Results: Median OS was 41.3 months (90% CI: 36.8-46.3) overall and 45.7 months (90% CI: 45.3-51.5) in patients with Del19-positive tumors (n = 149); 2-year survival was 80 and 82%, respectively. Updated median TTF with afatinib and osimertinib was 28.1 months (90% CI: 26.8-30.3). Conclusion: Sequential afatinib/osimertinib was associated with encouraging OS/TTF in patients with EGFR T790M-positive non-small-cell lung cancer, especially in patients with Del19-positive tumors.
Keywords: non-small cell lung carcinoma - therapy, drug therapy, afatinib, osimertinib, GioTag study
Published in DiRROS: 11.09.2020; Views: 1392; Downloads: 1014
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