Background and importanceIn managing chronic lymphocytic leukaemia (CLL), it is recommended that patients with TP53 deletion/mutation (TP53mut), who have a poor prognosis, are treated with ibrutinib ...as frontline therapy. Because of severe infectious complications, idelalisib combined with rituximab is only recommended for frontline therapy in patients not suitable for ibrutinib, if measures to prevent infection are followed. Patients unsuitable for ibrutinib/idelalisib may otherwise be treated with venetoclax.Aim and objectivesTo evaluate the prescriptions and clinical outcomes of ibrutinib, idelalisib and venetoclax in a third level hospital.Material and methodsAn observational, retrospective study was conducted including any prescriptions of ibrutinib, idelalisib and venetoclax for CLL from November 2015 to June 2019. We focused on TP53 mutation status, drug exposure, survival outcomes and reasons for drug switching or dose reduction, if applicable. Data were collected from electronic medical records.ResultsThirty patients receiving ibrutinib (n=23), idelalisib (n=13) and/or venetoclax (n=5) were recruited. Seventeen patients (56.7%) showed TP53mut. In the ibrutinib cohort, median drug exposure was 10.5 months and most patients (65.2%) had received it after conventional chemotherapy regimens (eg, FCR, R-CHOP, R-bendamustine). Only 5 patients (21.7%) showing TP53mut had taken ibrutinib as firstline therapy and 4 (17.4%) had received it after idelalisib; 2 of these patients because of disease progression and the other 2 because of adverse events (severe infections and colitis with weight loss). In the idelalisib cohort, median drug exposure was 4.45 months. Venetoclax was used for a median of 0.74 months and on ibrutinib failure in 4 patients (the remaining patient received prior idelalisib due to concomitant anticoagulant therapy). Dose reductions were needed in 11 patients on ibrutinib (causes: bruising, respiratory tract infections and neutropenia); in 4 receiving idelalisib due to severe diarrhoea (n=3) and pneumonia (n=1); and in 1 patient on venetoclax due to severe neutropenia. Neither median progression free survival nor median overall survival were reached at the data cut-off date. In fact, 59.5% of patients were still alive.Conclusion and relevanceMost patients received secondline ibrutinib and showed a long term response duration even when TP53mut was absent. Adverse effects resulted in frequent dose reductions/drug switching. However, venetoclax represents an appropriate option for patients whose CLL has failed to respond to ibrutinib/idelalisib.References and/or acknowledgementsNo conflict of interest.
Background and ImportancePharmacist validation of hospitalised patients’ medication is a fundamental task that spends much of the hospital pharmacist’s time.Aim and ObjectivesTo establish a protocol ...for optimisation of pharmaceutical validation through the analysis of the validation timetable of prescribing physicians.Material and MethodsA validation statistics report was carried out for the prescribing medical staff for the last 6 months (March 2022 to September 2022). In this, the total validations were divided into the 24 hours of the day, calculating the percent corresponding to each of the hours. With the results obtained, an analysis was made of the hours with the most validations per day. With this, the pharmacist validation was adapted to those hours in such a way that most prescriptions were reviewed shortly after being validated by the doctor, and the rest of time were left for other assistance tasks of the pharmacist.ResultsThe hours with the highest medical validation were 10 a.m. (15.98%) and 11 a.m. (13.52%), while the night hours (0 a.m. to 7 a.m.) had the least validation (0.06–1.03%). Therefore, the pharmaceutical validation schedules were adapted to the following:8 am: to review the treatments validated by the physician between 3 p.m. and 8 a.m. (hours in which the Pharmacy Service is closed), and which correspond to 27.48% of daily medical validations.11 am: to review the treatments accumulated in the hours with the highest medical validation. They correspond to 36.71% of daily medical validations.2 pm: to finish reviewing pending treatments before sending the medication to the patients (which is at 3 p.m). They correspond to 35.81% of daily medical validations.Conclusion and RelevanceOptimising the timetable of pharmaceutical validation allows the pharmacist to use the rest of the time in other care tasks, which has a positive impact on patients, while still being able to resolve any discrepancies found in the validation at the right time.References and/or AcknowledgementsConflict of InterestNo conflict of interest
Background and importanceApalutamide, enzalutamide and darolutamide have recently been approved for treating castration resistant non-metastatic prostate cancer (nmCRPC). The lack of direct ...comparisons makes the selection and positioning of these drugs in this new scenario difficult. Taking into account the social and economic importance, it is essential to develop studies that provide answers to this lack of information.Aim and objectivesThe aim of this study was to compare the relative efficacy of darolutamide versus apalutamide and enzalutamide using clinical trial data to determine the positioning of new antiandrogenic drugs in the treatment of nmCRPC.Material and methodsWe performed adjusted indirect comparisons using Bucher´s method. We selected the main clinical trial for each drug (ARAMIS, PROSPER and SPARTAN trials). The three studies had a similar design and included populations with similar characteristics. The main outcome used was metastasis free survival (MFS). MFS was demonstrated to be an adequate surrogate variable for overall survival.1 The variable used for darolutamide in the darolutamide versus enzalutamide IC was progression free survival (PFS) due to the PROSPER design. MFS and PFS were compared with placebo in the three studies.ResultsThe three drugs were superior to placebo for the endpoints analysed. In the comparison between enzalutamide (MFS=36.6 months (m) vs 14.7 m) versus darolutamide (PFS=36.8 m vs 14.8 m), HR calculated using Bucher’s method favoured enzalutamide (0.76 (IC 0.59–0.98); p=0.037). In the IC darolutamide (MFS=40.4 m vs 18.4 m) versus apalutamide (MFS= 40.5 m vs 14.7 m) HR favoured apalutamide (1.41 (IC 1.07–1.87); p=0.015). Both IC yielded a statistically significant result.Conclusion and relevanceWhile indirect comparisons had limitations, this analysis showed the slight superiority in HR in delaying the appearance of metastases for enzalutamide and apalutamide. Despite the data obtained, the inferiority of darolutamide cannot be assured. The biases involved in the comparison may have influenced the results. Real world data are needed to expand our knowledge of castration resistant non-metastatic prostate cancer treatment.References and/or acknowledgementsXie W, Regan MM, Buyse M, et al. Metastasis-free survival is a strong surrogate of overall survival in localised prostate cancer. J Clin Oncol 2017;35:3097–104.Conflict of interestNo conflict of interest
Background and importanceWith the arrival of SARS-CoV-2, it has been observed that the number of cases of fungal infection has increased in critically ill patients, especially invasive pulmonary ...aspergillosis (IPA).Aim and objectivesTo analyse the use of antifungals, expressed in defined daily dose per 100 annual hospital stays (DDD/100S), and the difference in economic impact between 2019 and 2020 in the intensive care unit (ICU) of a tertiary hospital.Material and methodsRetrospective descriptive study of the use of antifungals in the ICU unit during the period 2019–2020. The data were obtained from the STOCK-Athos-APD drug management electronic program and PRISMA electronic prescription program. For each antifungal agent, the following information was collected: annual global DDD, annual DDD/100S and economic cost of antifungal agents in both years. To calculate this expense the mean annual cost/stay was used.ResultsEight antifungals were studied (liposomal amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, voriconazole, posaconazole and isavuconazole). The registered stays for admission to the ICU were 5768 in 2019 and 5782 in 2020. The global DDD/100S of antifungals in 2019 was 37.73 while in 2020 it increased to 38.43.The antifungals with the highest increase were isavuconazole and posaconazole, with a difference of 4.2 and 5.1 DDD/100S, respectively, despite being antifungals of restricted use in our hospital. This increase is due to the rise in IPA cases and a period of shortage of voriconazole, the first-line antifungal in our hospital for IPA in patients without renal failure and without drugs with a possible interaction. However, there was a reduction in the DDD/100S of fluconazole. This is due to a greater number of patients with complicated candidaemia, long-term in the ICU who required a broad-spectrum antifungal such as caspofungin. DDD/100S of the rest of antifungals was not modified compared to the previous year. Therefore, the cost of antifungals in the ICU had an increase of €112 086.62 (43.8% more than in 2019).Conclusion and relevanceThe global DDD/100S of many antifungals in ICU has shown a slight increase between both years. The consumption of these has changed, and this has been manifested with an increment in economic spending as they are drugs with a greater economic impact.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and ImportanceSeveral monoclonal antibodies for preventive treatment of chronic migraine have been approved in recent years. However, there are no studies that directly compare these ...treatments.Aim and ObjectivesTo establish, through an indirect comparison (IC) against placebo, whether eptinezumab (Ep), galcanezumab (Ga), fremanezumab (Fre) and erenumab (Ere) could be considered equivalent alternatives in efficacy for the preventive treatment of chronic migraine.Material and MethodsA PubMed search was performed for pivotal clinical trials (CTs) of eptinetumab (300 mg/12 weeks), galcanezumab (240 mg/4 weeks), fremanezumab (675 mg/12 weeks) and erenumab (140 mg/4 weeks) for the preventive treatment of chronic migraine. The variable for comparison was the percentage of patients with ≥75% response (% of patients with a 75% reduction in migraine days per month) at week 12 after the start of treatment. With the results of ≥75% response, relative risk (RR) compared to placebo was calculated. Finally, with these values, an IC of these drugs was performed using the Bucher method (ITC calculator, Indirect Treatment Comparisons, of the Canadian Agency for Health Technology Assessment). The results were analysed, seeing if there were statistically significant differences between these four drugs.ResultsFour CTs were found, one with each drug, all of them compared to placebo as a common comparator. All the studies presented a similar methodology. However, CT of erenumab was a phase 2 CT, while the others were phase 3. Moreover, in the erenumab CT the sample size (667 patients) was smaller than in the other CTs (between 1072 and 1130 patients). These limitations for IC were eventually accepted. After applying the Bucher method, the following results were obtained:OR (Ep 300 mg vs Gal2 40 mg) 0,89 IC 95% 0,48–1,65; p=0,70OR (Ep 300 mg vs Fre 675 mg) 0,95 IC 95% 0,56–1,61; p=0,85OR (Ep 300 mg vs Ere 140 mg) 1,21 IC 95% 0,69–2,13; p=0,50OR (Fre 675 mg vs Gal 240 mg) 0,93 IC 95% 0,46–1,89; p=0,85OR(Ere 140 mg vs Gal 240 mg ) 0,73 IC 95% 0,35–1,52; p=0,40OR(Fre 675 mg vs Ere140 mg ) 1,28 IC 95% 0,66–2,46; p=0,47Conclusion and RelevanceAccording to the results obtained, given that no statistically significant differences have been established between the different drugs in terms of efficacy, the choice of one or the other should be based on safety and efficiency criteria. Nevertheless, it would be of special interest to have a direct comparison of these drugs to confirm the equivalence.References and/or AcknowledgementsConflict of InterestNo conflict of interest
Background and ImportanceSeveral oral drugs for atopic dermatitis have been approved in recent years. However, there are no studies that directly compare these treatments.Aim and ObjectivesTo ...establish, through an indirect comparison (IC) against placebo, whether abrocitinib, baricitinib and upadacitinib can be considered equivalent alternatives in efficacy for the treatment of atopic dermatitis, when used as monotherapy.Material and MethodsA PubMed search was performed for pivotal clinical trials (CTs) of abrocitinib (200 mg/24h), baricitinib (4 mg/24h), and upadacitinib (30 mg/24h) for atopic dermatitis, as monotherapy. The main variable for comparison was the results of the EASI75 (Eczema Area and Severity Index) at week 16 after the start of treatment. With the results of the EASI75 (%), the relative risk (RR) compared to placebo was calculated. Finally, with these values, an IC of these drugs was performed using the Bucher method (ITC calculator, Indirect Treatment Comparisons, of the Canadian Agency for Health Technology Assessment). The results were analysed, seeing if there were statistically significant differences between these three drugs.ResultsFive CTs were found, one with abrocitinib, two with baricitinib (CTB1, CTB2) and upadacitinib (CTU1, CTU2), all of them compared to placebo as a common comparator. All the studies presented a similar methodology. However, in the CT of abrocitinib, patients under 18 years of age were not included, while in upadacitinib (13.5%) and baricitinib (22%) they were. Moreover, in the abrocitinib CT the EASI75 is measured at 12 weeks while in the others at 16 weeks. These limitations for IC were eventually accepted. After applying the Bucher method, the following results were obtained:OR (abrocitinib 200 mg vs baricitinib 4 mg) 0,53 IC 95% 0,24–1,18; p=0,12 (in CTB1) and 0,65 IC 95% 0,27–1,54; p=0,32 (in CTB2),OR (abrocitinib 200 mg vs upadacitinib 30 mg) 0,92 IC 95% 0,46–1,82; p=0,81 (in CTU1) and 1,04 IC 95% 0,52–2,08;p=0,92 (in CTU2),OR (baricitinib 4 mg CTB1 vs upadacitinib 30 mg) 1,73 IC 95% 0,98–3,07; p=0,06 (in CTU1) and 1,95 IC 95% 1,08–3,52; p=0,03 (in CTU2),OR (baricitinib 4 mg CTB2 vs upadacitinib 30 mg) 1,42 IC 95% 0,73–2,73; p=0,30 (in CTU1) and 1,6 IC 95% 0,81–3,13; p=0,17 (in CTU2).Conclusion and RelevanceAccording to the results obtained, it could be that Upadacitinib 30 mg presented greater efficacy than Baricitinib 4 mg as it is the only IC that has given a statistically significant difference. However, due to the aforementioned limitations, these results should be taken with caution and safety and efficiency criteria should also be taken into account.Conflict of InterestNo conflict of interest
Background and importanceIn April 2020, the protocol for the use of intra-articular injections was updated within a multidisciplinary context with Pharmacy, Traumatology and Rehabilitation. Sodium ...hilauronate 60 mg/4 ml (Hyalone, high molecular weight) was included. According to the new protocol, the use of Adant One (low molecular weight hyaluronic acid) was approved for grades I-II according to the Kellgren–Lawrence index (IKL) or III-IV in cases where Hyalone is not tolerated due to pain. Hyalone was indicated for IKL grades II-III-IV.Aim and objectivesTo evaluate the healthcare and economic impact of the incorporation of a new presentation of hyaluronic acid in the intra-articular infiltration protocol of a regional hospital.Material and methodsRetrospective observational study and economic analysis of drugs used in intra-articular infiltration, comparing a period (period 1) prior to the update of the protocol (April 2019–April 2020), with another period (period 2) 1 year after the implementation of the protocol (April 2020–April 2021). Data were obtained from the electronic prescription program (number of patients, number of dispensations as well as cost per drug and total cost).ResultsThe data obtained are given in Table 1.Abstract 2SPD-020 Table 1 Parameter Period 1 Period 2 Patients (n) 91 94 Adant One (% of patients) 85.10 52.12 Adant (% of patients) 14.89 14.89 Hyalone (% of patients) – 32.97 Adant One cost (€) 5776.53 3367.39 Adant cost (€) 495 363 Hyalone cost (€) – 2803.8 Total costs (€) 6271.53 6534.14 In period 1, the Rehabilitation Service was the service that performed the most infiltrations (52.5% of the total patients treated with Adant One) and 92.85% of the total patients treated with Adant. In period 2, Adant One was used in a similar way. In the case of Hyalone, 96.77% was used by the Rehabilitation Service.Conclusion and relevanceThe introduction of the new presentation of hyaluronic acid allowed a better individualisation of the treatment of intra-articular infiltrations and did not lead to a noticeable cost increase.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceAcalabrutinib + obinutuzumab is authorised for the treatment of previously untreated patients with chronic lymphocytic leukemia (UPCLL), such as ibrutinib. Since comparative ...studies are not yet available, an indirect comparison (IC) between them could be of special interest.Aim and objectivesTo establish, through an IC versus obinutuzumab + clorambucil, whether acalabrutinib + obinutuzumab and ibrutinib + obinutuzumab can be considered equivalent therapeutic alternatives (ETA) in efficacy in the treatment of UPCLL.Material and methodsA PubMed search of pivotal clinical trials (CTs) responsible for the authorisation of both drugs was performed. Progression-free survival (PFS) results were taken as the main variable for comparison. IC were performed using the Bucher method (indirect treatment comparisons calculator, Canadian Health Technology Assessment Agency) of UPCLL from both trials. The reference value used for the sample calculation in ibrutinib + obinutuzumab CT was hazard ratio (HR)=0.55 and HR=0.60 in acalabrutinib + obinutuzumab CT, therefore a delta (Δ) of 0.6 was set as the most clinically relevant value. With this value, acalabrutinib + obinutuzumab was compared with ibrutinib + obinutuzumab in PFS and the results were analysed to see if the confidence intervals (95% CI) were within the ±Δ interval. The methodology of the Spanish ETA-Guide1 (a tool that allows assessment of the clinical equivalence of two or more drugs and position them) was applied.ResultsTwo CTs were found, one with acalabrutinib + obinutuzumab and another with ibrutinib + obinutuzumab, both against obinutuzumab + clorambucil as a common comparator. Both studies had a similar methodology. However, in the ibrutinib + obinutuzumab trial, patients with small lymphocytic lymphoma were included, although they were minority (5%). This limitation for IC was accepted. After applying the Bucher method, a HR=0.435 (95% CI 0.218 to 0.866) was obtained for acalabrutinib + obinutuzumab versus ibrutinib + obinutuzumab. According to the ETA-Guide, in the comparative efficacy of both drugs, a D position was obtained: graphically, the 95% CI was positioned almost completely within the ±Δ interval. Therefore, the difference is probably irrelevant. However, as treatment failure involves a serious prejudice for the patient, according to this guide they would be considered not ETA.Conclusion and relevanceAccording to the ETA criteria, acalabrutinib + obinutuzumab and ibrutinib + obinutuzumab could not be considered ETA, since after IC a greater benefit was observed with acalabrutinib + obinutuzumab. Nevertheless, safety and efficiency criteria should also be taken into account.References and/or acknowledgements1. Med Clin (Barc) 2014;143(2):85–90.Conflict of interestNo conflict of interest
Background and ImportanceThere is limited evidence on the preparation of intrathecal (IT) trastuzumab.Aim and ObjectivesTo define a formulation of IT trastuzumab (in combination with hydrocortisone ...and methotrexate), for a woman with metastatic breast cancer, HER2+, with meningeal carcinomatosis and brain metastases.Material and MethodsA bibliographic search was carried out in several sources (Google Scholar, PubMed, Uptodate) to find case reports (keywords Trastuzumab + Intrathecal/Intrathecal). Only the articles that described the methodology of preparation (at least the reconstitution) were selected. Based on the available evidence, the formulation of IT trastuzumab was defined.ResultsOnly 4 articles were identified (5 cases). The periodicity of the maintenance doses was always 7 days. Attending at the product used in the reconstitution, 2 articles specified ‘diluent without preservatives’. 2 articles described the fully process: the vial of trastuzumab 150 mg is reconstituted with 7.2 ml of sterile water and were elaborated IT doses from 20 mg to 100 mg. 1 article specified that the patient received IT methotrexate 12 mg followed by IT trastuzumab and in the other article IT trastuzumab was administered first, followed by IT methotrexate 15 mg, and finally IT hydrocortisone 24 mg.Based on the available evidence we reconstituted 1 vial of 150 mg (from a biosimilar presentation that contained the same excipients as the first authorised brand of trastuzumab) with 7.2 ml of sterile water for injections. A 25 mg (1.2 mL) dose was refilled into a polypropylene immediate-use syringe.The patient also needed IT methotrexate and IT hydrocortisone (both prepared in separate polypropylene syringes) and the administration sequence was: methotrexate 12 mg/ 4.8ml (obtained from methotrexate 50 mg/2ml diluted with 0.9% sodium chloride), hydrocortisone 20 mg/ 0.2 ml (obtained from hydrocortisone 100 mg reconstituted with 0.9% sodium chloride) followed by trastuzumab 25 mg/1.2 ml.Although the patient died after receiving 2 doses (separated by 7 days), did not present any complications due to the administration (no headache, nausea or vomiting).Conclusion and RelevanceDue to the limited information about the elaboration of IT trastuzumab, is important to have available new evidence. Our formulation also use a biosimilar presentation of trastuzumab, which was safe and well tolerated.References and/or AcknowledgementsConflict of InterestNo conflict of interest
Background and importanceAnti-PD-L1 immunotherapy is used to treat secondline or later non-small cell lung cancer (NSCLC). These monoclonal antibodies are the therapy of choice against NSCLC in ...routine clinical practice.Aim and objectivesTo evaluate the efficacy of anti-PD-L1 immunotherapy in clinical practice in NSCLC.Material and methodsThis retrospective observational study (July 2017 to July 2020) evaluated the efficacy of atezolizumab, nivolumab and pembrolizumab in patients with NSCLC, in a tertiary hospital, after failing firstline chemotherapy. The study variables were progression free survival (PFS) and overall survival (OS). Patient data were obtained through the digital medical record and the Oncowin oncology pharmacy computer programme.Results85 patients were included (23 received atezolizumab, 47 received nivolumab and 15 pembrolizumab). Mean age was 66 years and 89.4% were men. After a follow-up of 72 months, median OS of atezolizumab was 15.75 months (95% CI 0.00 to 33.08), nivolumab 4.7 months (95% CI 2.87 to 6.58) and pembrolizumab 13.73 months (95% CI 4.47 to 22.99). Median PFS for atezolizumab was 6.83 months (95% CI 4.89 to 8.77), for nivolumab 3.12 months (95% CI 2.14 to 4.10) and for pembrolizumab 9.13 months (95% CI 0.48 to 17.70). Our results were compared with the results of pivotal clinical trials.For atezolizumab, median PFS of our study was much higher than that of the OAK1 study. Median OS was also higher than that of the OAK and POPLAR2 studies. The PFS results from our study of nivolumab were similar to those obtained in the CheckMate-0573 and CheckMate-CA2090174 trials. For OS, we found a much smaller median than that of the pivotal trials. For pembrolizumab, median PFS was higher than that in the Keynote 010 trial,5 although the OS values were the same.Conclusion and relevanceOur data indicated that the efficacy of anti-PDL1 immunotherapy in patients with secondline NSCLC in clinical practice varies with respect to the results obtained in pivotal clinical trials, with a higher PFS and a similar OS, except for nivolumab, which was much lower. It would be interesting, in future studies, to increase the number of patients to confirm these data on the efficacy of anti-PDL1 immunotherapy.References and/or acknowledgementsConflict of interestNo conflict of interest
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