Francisco Batel Marques

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines.

In all pivotal trials of COVID-19 vaccines, the history of previous SARS-CoV-2 infection was mentioned as one of the main exclusion criteria. In the absence of clinical trials, observational studies are the primary source for evidence generation. This study aims to describe the patient-reported adverse drug reactions (ADRs) following the first COVID-19 vaccination cycle, as well as the administration of booster doses of different vaccine brands, in people with prior SARS-CoV-2 infection, as compared to prior infection-free matched cohorts of vaccinees. A web-based prospective study was conducted collecting vaccinee-reported outcomes through electronic questionnaires from eleven European countries in the period February 2021–February 2023. A baseline questionnaire and up to six follow-up questionnaires collected data on the vaccinee’s characteristics, as well as solicited and unsolicited adverse reactions. Overall, 3886 and 902 vaccinees with prior SARS-CoV-2 infection and having received the first dose or a booster dose, respectively, were included in the analysis. After the first dose or booster dose, vaccinees with prior SARS-CoV-2 infection reported at least one ADR at a higher frequency than those matched without prior infection (3470 [89.6%] vs. 2916 [75.3%], and 614 [68.2%] vs. 546 [60.6%], respectively). On the contrary side, after the second dose, vaccinees with a history of SARS-CoV-2 infection reported at least one ADR at a lower frequency, compared to matched controls (1443 [85.0%] vs. 1543 [90.9%]). The median time to onset and the median time to recovery were similar across all doses and cohorts. The frequency of adverse reactions was higher in individuals with prior SARS-CoV-2 infection who received Vaxzevria as the first dose and Spikevax as the second and booster doses. The frequency of serious ADRs was low for all doses and cohorts. Data from this large-scale prospective study of COVID-19 vaccinees could be used to inform people as to the likelihood of adverse effects based on their history of SARS-CoV-2 infection, age, sex, and the type of vaccine administered. In line with pivotal trials, the safety profile of COVID-19 vaccines was also confirmed in people with prior SARS-CoV-2 infection.

Background: Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate. Aim: This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis. Method: Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp–Hartung method and Bayesian random-effects. Results: Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76–0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn’t significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89–1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses. Conclusion: Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.

Background: Topical Janus kinase (JAK) inhibitors are being developed for the treatment of mild to moderate atopic dermatitis. However, comparative evidence on their safety profiles is still limited. Aim: This study aimed to compare the relative safety of topic JAK inhibitors in patients with atopic dermatitis. Method: Phase 2 and 3 clinical trials (RCTs) evaluating the efficacy and safety of topical JAK inhibitors in atopic dermatitis were searched on Medline, EMBASE and clinicaltrials.gov. The following outcomes were considered: any adverse event (AE), serious AEs, AEs leading to treatment discontinuation, any infection, any application site reaction. Results: Ten RCTs were included in this network meta-analysis. Tofacitinib was associated with a reduced risk of any AE when compared with ruxolitinib (OR 0.18, 95% CrI 0.03–0.92). The analyses for the remaining outcomes did not identify other statistically significant risk differences between the topical JAK inhibitors. Conclusion: Although tofacitinib seems to present a reduced risk of any adverse event compared with ruxolitinib, this was the only statistically significant result found between JAK inhibitors. Therefore, such findings should be interpreted with caution considering the scarce data available and the heterogeneity between the studies, and there is no robust evidence allowing pointing out clinically important differences between the safety profiles of the existing topical JAK inhibitors. Further pharmacovigilance activities are needed to confirm the safety profile of these drugs.

According to international research, an increase in the patient share of pharmaceutical expenditure results in a decrease in medicines utilization. In 2010, the Portuguese government reduced the re...

Background/Objective: This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in the treatment of postmenopausal osteoporosis. Methods: This systematic review was conducted in accordance with the Centre for Reviews and Dissemination's guidance and reporting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement 2020. A literature search was performed in PubMed and EMBASE since their inception until February 7, 2022. Randomized controlled trials (RCTs), meta-analysis, experimental, and observational studies evaluating adult patients treated with ibandronate and assessed to osteoporotic fractures prevention were included. The risk of bias was assessed according to study design. Data were analyzed using descriptive statistics. Results: Eight references from 4 RCTs, 7 meta-analyses, and 6 observational studies were included. In RCTs, oral ibandronate was superior to placebo in the prevention of VF. However, the doses were lower than those approved. The meta-analyses confirmed these results and showed that adequate doses of oral ibandronate reduce the risk of NVF compared with insufficient doses. In observational studies, oral ibandronate (in approved doses) reduced the risk of VF compared with no treatment or risedronate or alendronate and the risk of NVF versus risedronate or alendronate; the risk of hip fractures was similar between ibandronate and other oral bisphosphonates. Conclusions: There is strong evidence that ibandronate reduces the risk of VF in postmenopausal osteoporosis. The available evidence further suggests that ibandronate may reduce the risk of NVF versus insufficient doses of ibandronate, as well as risedronate or alendronate.

Background and importance The use of biologics is essential in the management of several types of cancer. When patents of reference biologics expired, biosimilars emerged, widening the patient‘s access to biological therapy and providing cost savings to healthcare systems. The hospital pharmacist stands in a privileged position, structuring post-marketing surveillance and implementing active pharmacovigilance programmes to monitor the safety of these technologies. Aim and objectives The aim of this study was to evaluate the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital using an intensive monitoring programme. Material and methods This hospital based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima) or trastuzumab biosimilar CT-P6 (Herzuma) were recruited over an 11 month and a 6 month period (from 1 November 2018 and 1 April 2019, respectively, until 30 November 2019). A paper based ADR reporting form was developed for each biosimilar medicine and completed by clinicians. Clinical secretariats sent the reports through an electronic platform to the pharmacovigilance department for analysis of seriousness, expectedness and causality of suspected ADRs. Results 94 patients received biosimilar medicines (rituximab, n=35; trastuzumab, n=59). Of these, 4 (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related to the biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 (Truxima) was chest discomfort (n=4; 19.1%), followed by odynophagia (n=2; 9.5%). Trastuzumab CT-P6 (Herzuma) was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n=1; 4.8%). Conclusion and relevance The results of this study suggest that in the real world setting, the biosimilar rituximab and biosimilar trastuzumab to treat cancer patients were associated with acceptable safety profiles. No new safety problems were identified. Also, the results of this study showed that carrying out active pharmacovigilance programmes in oncology pharmacy practice is feasible and that such activities contribute to better characterisation of the safety profiles of medicines. Conflict of interest No conflict of interest

Physicians must acknowledge the potential risk of RSH with enoxaparin. Switching home anticoagulation by enoxaparin upon hospital admission is common, but it may put patients at higher risk for RSH. Management guidelines are needed in this setting.

Purpose: To characterize the effectiveness measures of cost‐effectiveness studies (CES) of ophthalmic drugs.Methods: A systematic review was conducted in PubMed/Embase until October 2019. Cost‐effectiveness studies (CES) evaluating ophthalmic drugs were included. Sources of effectiveness measures were extracted. Data on study design and study outcomes were extracted from sources of effectiveness measures. The adequacy of the sample size of the clinical studies used as sources of effectiveness measures was assessed. If CES have retrieved effectiveness data from multiple sources, the appropriateness of the method to combine the results was analysed.Results: Forty‐five CES were included. Thirty‐one (68.9%) retrieved their effectiveness measures from experimental studies, five (11.1%) from observational studies and nine (20%) from other type of data sources. Eight (17.8%) CES used data from a primary outcome of a study as an effectiveness measure, eight (17.8%) used data from secondary outcomes, seven (15.6%) used data from the both primary and secondary outcomes and for 22 (48.9%) it was not possible to identify the outcomes used. From the 23 (51.1%) CES based on a single clinical study, three (6.7%) included data from clinical studies which had an adequate sample size to detect significant differences in the clinical outcomes used as effectiveness measures. From the 17 (37.8%) CES based on multiple clinical studies, only one (2.2%) used and/or reported an adequate method of quantitative synthesis (meta‐analysis).Conclusion: A considerable number of CES in ophthalmology were not based on clinical studies with adequate sample sizes and report results from effectiveness measures not assessed as primary outcomes.