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Purpose: To examine the adherence to risk minimization measures (RMMs) in newly treated patients with anti‐tumor necrosis factor‐alpha (anti‐TNF‐α) medications at one of the largest tertiary care hospitals in Saudi Arabia. Methods: We included patients who had at least one prescription of infliximab or adalimumab. The index date was the first recorded date of infliximab or adalimumab prescription. New users of anti‐TNF‐α were divided into pre‐ and post‐RMM implementation groups. The outcome of interest was the proportion of patients that received tuberculosis (TB) screening, including a chest X‐ray (CXR) or a QuantiFERON test within 1 month prior to the index date. Results: A pre‐post RMM implementation comparison of TB screening among infliximab users showed a significant increase in the rates of CXR tests (from 7.5% before RMM implementation to 13.8% after RMM implementation, p < 0.001) and the rates of QuantiFERON tests (4.5% before RMM implementation to 24.1% after RMM implementation, p < 0.001). RMMs were introduced to the study site at the same time as adalimumab was approved and the proportion of patients receiving TB screening was 25.2%. Conclusion: TB screening prior to initiation of infliximab or adalimumab was not optimal. However, we noted an improvement in TB screening after the implementation of RMMs for infliximab. Future research may address reasons for low adherence to testing requirements for TB prior to initiation of anti‐TNF‐α medications. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC. [ABSTRACT FROM AUTHOR]

Biopharmaceuticals have emerged as a cornerstone of modern medicine, offering targeted and effective treatments for a diverse array of medical conditions. This review provides an overview of the key applications, challenges, and opportunities in biopharmaceutical development. Key applications include cancer immunotherapy, rare genetic disorders, autoimmune diseases, infectious diseases, and neurological disorders. Challenges such as complex manufacturing processes, regulatory requirements, and high costs are discussed, alongside opportunities arising from advances in biotechnology, personalized medicine, and collaborative partnerships. The importance of prioritizing patient safety, accessibility, and affordability is emphasized. By embracing innovation and collaboration, the biopharmaceutical industry can continue to revolutionize healthcare and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Summary: Tirzepatide is a new glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) that has shown promising results for weight loss. A Bayesian network meta‐analysis was conducted to compare the efficacy and safety of GLP‐1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP‐1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%–20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder‐related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%–20% weight loss compared with liraglutide. GLP‐1RAs triggered more gastrointestinal adverse events than placebo, with no in‐between difference. Although all GLP‐1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile. [ABSTRACT FROM AUTHOR]

To assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer. A 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients' access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD). Rixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima. Rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access. [ABSTRACT FROM AUTHOR]

Aim: To determine the incidence of chemotherapy-induced febrile neutropenia (FN) and related outcomes after same-day pegfilgrastim in lung cancer. Materials & methods: This single-center, retrospective study evaluated electronic health records of patients with lung cancer treated between 2013-2018. The main end points were incidence of FN and grade 3/4 neutropenia after the first and across all chemotherapy cycles. Results: A total of 114 patients received same-day pegfilgrastim in 384 cycles. The incidence of FN and grade 3/4 neutropenia was 2.3 and 25% after the first chemotherapy cycle and 1.6 and 10.4% across all cycles, respectively. Conclusion: Same-day prophylactic pegfilgrastim in patients with lung cancer may be a suitable option, owing to its low incidence of FN and related outcomes. [ABSTRACT FROM AUTHOR]

To perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs. A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021–2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis. The CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA. Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs. [ABSTRACT FROM AUTHOR]

The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69–3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI. [ABSTRACT FROM AUTHOR]

Background: Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1 diabetes. This systematic review and meta-analysis aimed to estimate the risk of DKA, including severe DKA, during the COVID-19 pandemic versus the prior-to-COVID-19 period among pediatric patients with type 1 diabetes. Methods: PubMed and EMBASE were searched for observational studies investigating the risk of DKA among pediatric patients with type 1 diabetes during the COVID-19 pandemic and the prior-to-COVID-19 period. A random meta-analysis model was performed to estimate the relative risk of DKA during the COVID-19 pandemic compared to before the pandemic. Subgroup analyses were conducted based on the type 1 diabetes status, established or newly diagnosed. In addition, sensitivity analysis was conducted for studies that reported results from adjusted analysis for potential confounders using fixed effect model. Results: A total of 20 observational studies reported the risk of DKA, of which 18 reported the risk of severe DKA. The risks of DKA and severe DKA were 35% (RR 1.35, 95%CI 1.2-1.53, I 2 = 71%) and 76% (RR 1.76, 95%CI 1.33-2.33, I 2 = 44%) higher in the during-COVID-19 group compared to the prior-to-COVID-19 group, respectively. Among patients with newly diagnosed type 1 diabetes, the risk of DKA was 44% higher for the during-COVID-19 group compared to the prior-to-COVID-19 group (RR 1.44, 95%CI 1.26-1.65; I 2 = 64%). Only two studies reported the risk of DKA among patients with established type 1 diabetes and the cumulative risk was not statistically significant. In the sensitivity analysis, four studies reported an adjusted odds ratio (aOR) of the risk of DKA during COVID-19 compared to the prior-to-COVID-19 period. The fixed estimate from the meta-analysis found an increase in the risk of DKA in the during-COVID-19 group compared to the prior-to-COVID-19 group (aOR 2.04, 95%CI 1.66-2.50). Conclusions: This study showed that DKA risk, especially the risk of severe DKA, has increased significantly during the pandemic. Healthcare systems must be aware and prepared for such an increase in DKA cases and take all necessary measures to prevent future spikes during the pandemic. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=272775 , identifier PROSPERO [CRD42021272775]. [ABSTRACT FROM AUTHOR]

Purpose: The main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a "real-world" setting. Patients and Methods: A retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥ 18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up. Results: Among the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6± 19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53– 1.68), including DVT (AOR=1.06; 95% CI 0.52– 2.17) and PE (AOR=0.78; 95% CI 0.31– 1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04– 0.83). Conclusion: The use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events. [ABSTRACT FROM AUTHOR]

Background: The use of ipilimumab, nivolumab, and pembrolizumab as monotherapies or in combination has transformed the management of advanced melanoma even though these drugs are associated with a new profile of immune-related adverse events (irAEs). The incidence of irAEs from clinical trials of these agents is an important factor for clinicians when treating patients with advanced melanoma. In the current study, we aimed to profile the incidence of potential irAEs of these agents when used as monotherapy and as combination therapy. Methods: We searched the Medline, Embase, and Cochrane databases; clinicaltrials.gov; and websites of regulatory agencies in the USA, Europe, Australia, and Japan for phase 1–3 trials of ipilimumab, nivolumab, and pembrolizumab for advanced melanoma. Random effect meta-analysis was utilized to profile the incidence of potential irAEs. Results: A total of 58 reports of 35 trials including 6,331 patients with advanced melanoma and reporting irAE data were included in the meta-analyses. We found higher incidences of potential irAEs in combination therapies vs. monotherapies for most of the types of irAEs. Among the monotherapies, ipilimumab users had the most frequent incidence of potential irAEs related to the gastrointestinal system (diarrhea, 29%; and colitis, 8%) and skin (rash, 31%; pruritus, 27%; and dermatitis, 10%), with hypophysitis in 4% of the patients. The most frequent potential irAEs among nivolumab users were maculopapular rash (13%), erythema (4%), hepatitis (3%), and infusion-related reactions (3%), while they were arthralgia (12%), hypothyroidism (8%), and hyperglycemia (6%), among pembrolizumab users. Conclusion: Especially the combination therapies tend to elevate the incidence of potential irAEs. Clinicians should be vigilant about irAEs following combination therapy as well as gastrointestinal and skin irAEs following ipilimumab therapy, in addition to being aware of potential irAEs leading to hyperglycemia, thyroid, hepatic, and musculoskeletal disorders following nivolumab and pembrolizumab therapy. [ABSTRACT FROM AUTHOR]

Objectives The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to- head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients. Design A systematic review and Bayesian network meta-analysis. Data source A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials. gov). Eligibility criteria RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome. Data extraction and synthesis We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. Results Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events. Conclusions This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab. [ABSTRACT FROM AUTHOR]

Background: Multimodal and multidomain strategies are currently recommended for the management of chronic pain. However, there is little information available on how individuals (opioid users versus nonusers) with chronic pain use multimodal strategies in pain management.Methods: This cross-sectional study used questionnaire data from a sample of pharmacists with chronic pain. The questionnaire collected data on demographics, pain characteristics, pain management strategies, and pain management outcomes. The association between the number of strategies used and opioid use were evaluated by linear regression. Differences between the groups in nonsteroidal anti-inflammatory drugs (NSAIDs) use and types of strategies used in managing the pain were analyzed using logistic regressions. A hierarchical logistic regression was performed to identify potential predictors differentiating opioid users from nonusers.Results: Fifty-seven opioid users and 100 nonusers with chronic pain completed the questionnaire. Opioid users reported higher levels of pain at baseline (7.6 ± 1.7 vs. 6.7 ± 2.2; P = 0.011); however, pain levels after treatment were comparable (2.9 ± 1.9 vs. 3.2 ± 2.4; P = 0.33). Although there was no significant difference in the total number of strategies, the number of pharmacologic strategies was significantly higher in opioid users (P = 0.007). The type of pain management strategies and the use of NSAIDs were similar in both groups after adjusting for potential confounders. The significant predictors of opioid use from hierarchical logistic regression analysis were: lower use of over-the-counter NSAIDs (odds ratio [OR] 0.4; 95% CI 0.2-0.9), using more interventions (OR 1.2; 95% CI 1.1-1.3), reliance on pharmacologic strategies (OR 10.8; 95% CI 2.1-55.7), using combination of pharmacologic and nonpharmacologic strategies (OR 3.7; 95% CI 0.9-15.8), and less interference with daily activities after treatment (OR 0.2; 95% CI 0.1-0.9).Conclusion: Opioid use was primarily related to the use of prescription pharmacologic strategies, but not to age or gender. Posttreatment pain levels were similar between opioid users and nonusers; however, opioid users used more nonopioid medications than nonusers did. [ABSTRACT FROM AUTHOR]

Objective: To indirectly compare glucagon like peptide-1 receptor agonists (GLP-1RA) cardiovascular outcome trials (CVOTs) using network meta-analysis (NMA). Methods: We searched Medline to retrieve CVOTs that involved GLP-1RA. We conducted NMAs using binomial likelihood logit link model for the following outcomes: CV death, myocardial infarction (IM), stroke, and death from any cause. After running both fixed effects and random effects models for each outcome, we identified the best fit model that has the smallest deviance information and the average posterior residual deviance. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA) in reporting this NMA. Results: After screening, a total of seven GLP-1RA CVOTs were included. The NMA results showed that oral semaglutide was statistically better than exenatide (HR 0.47, CI: 0.21-0.99), dulaglutide (HR 0.46, CI: 0.20-0.97), albiglutide (HR 0.45, CI: 0.19-0.97), and lixisenatide (HR 0.43, CI: 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (>90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events. Conclusion: The indirect comparison of GLP-1RAs using CVOTs data showed that oral semaglutide is preferred over most of the GLP-1RAs in reducing CV death and death from any cause events. The ranking probability showed that once weekly semaglutide and oral semaglutide are the most likely to be ranked first in reducing the outcomes of interest. Disclosure: O. Alfayez: None. O. Alkhezi: None. A.R. Almutairi: None. [ABSTRACT FROM AUTHOR]

Introduction: The government of the Kingdom of Saudi Arabia (KSA) has developed a well-defined strategy to restructure the health sector and operate on value-based principles. Biosimilars are a viable option for increasing accessibility while lowering health-care costs., Areas Covered: We describe the current and future biosimilar landscape in KSA. We discuss the growth of the biosimilar market, the regulatory approval process, biosimilar adoption, and the potential impact on health-care systems and patient outcomes., Expert Opinion: The biosimilar market in KSA is expanding and expected to continue this trajectory in the coming decade. The growth of the market is influenced by the KSA health transformation initiative, the well-defined regulatory framework for biosimilars set by the Saudi Food and Drug Authority (SFDA), and the adoption of biosimilars by health-care providers. Overall, the biosimilar regulation is evolving and the future of biosimilars looks promising in KSA. Biosimilars offer a more cost-effective alternative, which can help to expand access to more treatment options for patients and contribute to cost saving for the health-care system.

Purpose: The main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a "real-world" setting., Patients and Methods: A retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up., Results: Among the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6±19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53-1.68), including DVT (AOR=1.06; 95% CI 0.52-2.17) and PE (AOR=0.78; 95% CI 0.31-1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04-0.83)., Conclusion: The use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events., Competing Interests: Haya A Alkuait is an employee of SPIMACO Addwaeih. Wejdan Alobaidi is an employee of Novo Nordisk. Anas Aldawsari is an employee of Sanofi. Nouf M. Almutairi is an employee of BAYER pharmaceuticals. All authors report no other conflicts of interest in this work., (© 2021 Al Yami et al.)

Background: The risk of immune-related(ir)-hypothyroidism in older patients with advanced melanoma treated with anti-CTLA4 or anti-PD1 therapies is poorly understood, especially in the real-world setting. Research design and methods: We identified older patients (≥65 years) diagnosed with advanced melanoma between 2011-2015 and treated with anti-CTLA4 or anti-PD1 agents in the SEER-Medicare database. Applying probability-of-treatment-weighting for confounder adjustment and proportional hazards models, we estimated the risk of ir-hypothyroidism between treatment initiation and up to 90 days from last dose between anti-PD1 and anti-CTLA4 users. Results: Of 210 older patients with advanced melanoma identified, 164 received anti-CTLA4 (ipilimumab) and 46 anti-PD1 agents (11 nivolumab, 35 pembrolizumab). There was no statistically significant difference in ir-hypothyroidism risk between anti-PD1 and anti-CTLA4 users (HR=2.15, 95%CI=0.83-5.53). Pairwise medication comparisons showed a lower risk among ipilimumab versus nivolumab (HR=0.15, 95%CI=0.06-0.40) and pembrolizumab versus nivolumab users (HR=0.13, 95%CI=0.03-0.55). Sensitivity analyses using an all-stages melanoma cohort did not show a difference in ir-hypothyroidism risk between medication classes and individual medications. Conclusions: This retrospective claims data analysis revealed no statistically significant difference in ir-hypothyroidism risk between anti-CTLA4 or anti-PD1 users. However, patients with advanced melanoma treated with ipilimumab or pembrolizumab may have a lower ir-hypothyroidism risk compared to nivolumab users.

Objective: Creating an appropriate antithrombotic therapy for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) remains a dilemma. Several clinical trials compared the use of a dual antithrombotic therapy (DAT) regimen with a direct oral anticoagulants including (apixaban, dabigatran, edoxaban or rivaroxaban) and a P2Y 12 inhibitor versus a triple antithrombotic therapy (TAT) that includes a vitamin K antagonist plus aspirin and a P2Y 12 inhibitor in patients with AF who have undergone PCI. However, there are no head-to-head trials comparing the DAT regimens to each other. We aimed to compare the efficacy and safety of DAT regimens using a network meta-analysis (NMA) approach., Design: A systematic review and NMA of randomised clinical trials., Methods: We conducted a systematic literature review to identify relevant randomised clinical trials and performed a Bayesian NMA for International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, all-cause mortality, stroke, myocardial infarction (MI) and stent thrombosis outcomes. We used NetMetaXL V.1.6.1 and WinBUGS V.1.4.3 for the NMA and estimated the probability of ranking the treatments based on the surface under the cumulative ranking curve., Results: The comparison between DAT regimens showed no significant difference in the safety or efficacy outcomes. Apixaban regimen was ranked first as the preferred therapy in terms of ISTH major or CRNM bleeding and stroke, with a probability of 52% and 54%, respectively. Rivaroxaban regimen was the preferred therapy in terms of MI and stent thrombosis, with a probability of 34% and 27%, respectively. Dabigatran regimen was ranked first in terms of all-cause mortality, with a probability of 28%., Conclusion: The DAT regimens are as safe and effective as TAT regimens. However, ranking probabilities for the best option in the selected outcomes can be used to guide the selection among these agents based on different patients' conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives : To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors. Methods : The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses. Results : One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I 2  = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I 2  = 87.9%). Conclusion : The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.