Diogo Mendes

Background: Statins are a cornerstone of therapy to reduce LDL cholesterol and cardiovascular diseases. However, their use may cause adverse events. This umbrella review aims to comprehensively review the safety profile of statin therapy. Methods: PubMed and Embase were searched to identify systematic reviews, scoping reviews, meta-analyses and network meta-analyses on statin safety. Extracted data included study type, data source, number of included studies, search date range, participant numbers, interventions, safety outcomes, results and funding. Risk of bias was assessed using the AMSTAR 2 instrument. Data underwent descriptive statistical analysis. Results: Seventy-two reviews were included, mostly based on clinical trials (70.8%) and observational studies (59.7%). Only 21 (29.2%) reported results for individual statins, with atorvastatin being the most frequently evaluated individual statin (95.2%). Nearly 86% of the reviews were rated as Critically Low in overall confidence. Statins were associated with an increased risk of new-onset diabetes, particularly rosuvastatin and atorvastatin, whereas pitavastatin may be protective. Liver injury/dysfunction and elevated transaminases were observed, along with a small risk of muscle-related symptoms, specifically at higher statin intensity. Rare serious events, such as necrotising myopathy, were reported. Pregnancy studies indicated an increased risk of spontaneous abortion. Conclusion: Although overall statin safety is favourable, the risks of diabetes, liver dysfunction, enzyme elevations and muscle symptoms require consideration, especially with high-intensity therapy or specific statins. Pitavastatin may be a safer option for patients at metabolic risk. Therapy should be tailored to individual patient factors. Further research is needed to clarify rare or inconsistent outcomes.

Aims: Once‐weekly basal insulins, icodec and efsitora alfa, were developed to improve treatment adherence and glycemic control and appear to be as effective as once‐daily degludec in reducing HbA1c in type 1 diabetes (T1DM). However, higher rates of clinically significant hypoglycemias were associated with both once‐weekly insulins. This network meta‐analysis compares the efficacy and safety of once‐weekly and once‐daily basal insulins in T1DM. Methods: PubMed and Embase were searched (up to April, 2025) to identify phase 3 clinical trials evaluating basal insulins in T1DM (icodec, efsitora alfa, degludec 100, glargine [100 and 300], detemir, and NPH). Change in HbA1c and weight, risk of hypoglycemias (overall and severe), and serious adverse events (AEs) were assessed at week 26 and 52. Results: Nineteen studies were included. At week 52, icodec reduced HbA1c more than degludec 100 (−0.17% [95% CrI: −0.28; −0.06]), glargine 100 (−0.17% [95% CrI: −0.32; −0.02]), detemir (−0.17% [95% CrI: −0.32; −0.02]), and NPH (−0.59% [95% CrI: −0.85; −0.34]), while efsitora alfa reduced HbA1c more than NPH (−0.45% [95% CrI: −0.70; −0.19]). Icodec showed a higher overall hypoglycemia risk at week 52 compared with degludec 100 (OR 1.64; 95% CrI 1.07–2.54) and detemir (OR 2.08; 95% CrI 1.01–4.39), but no increased risk of severe hypoglycemias or serious AEs. Conclusions: In T1DM, once‐weekly basal insulins appear broadly comparable in reducing HbA1c at week 52. Although icodec showed a higher overall hypoglycemia risk, evidence suggests a comparable risk of severe hypoglycemias between treatments.

Introduction: Reimbursement appraisals of medicines should emphasize outcomes clinically relevant to patients and clinicians. This study aims to characterize the outcomes selected in oncology reimbursement appraisal reports in Portugal. Methods: A cross-sectional analysis of public INFARMED pharmacotherapeutic appraisal reports for oncology medicines published in 2023–2024 was conducted. For each included report, we extracted efficacy and safety outcomes, their clinical relevance rating (critical/important), whether data were presented for analysis, and which outcomes were prioritized in the final decision rationale. Descriptive statistics were employed. Results: Fifty-four oncology reimbursement appraisals met the inclusion criteria. Overall survival was rated critical in 52/54 reports (96.3%) and prioritized in 29 (53.7%). Progression-free survival was rarely rated critical (n = 2, 3.7%) and was more often deemed important (n = 49, 90.7%), being prioritized in 15 (27.8%) reports. Quality of life was rated as critical in 52 (96.3%) reports but prioritized in only one (1.8%) decision. For safety, grade 3 to 4 AEs and mortality were graded as critical in 51 (94.4%) reports each, followed by discontinuation due to AEs (n = 50, 92.6%), although none of the appraisals prioritized safety outcomes in the final reimbursement decision. Conclusions: Overall survival predominates as the most influential outcome in Portuguese oncology drug reimbursement decisions. Progression-free survival is frequently used as a practical surrogate. Although quality of life and safety outcomes are commonly prioritized during scope-setting, they are not consistently reflected in decision rationales, underscoring the need to strengthen outcome reporting and evidence generation to better inform patient-centered reimbursement decisions.

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.

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.