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Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab. [ABSTRACT FROM AUTHOR]

BackgroundAdverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.MethodsA multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.FindingsSubstantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.InterpretationOur findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.FundingNone.

The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified. [ABSTRACT FROM AUTHOR]

Isolated cases of subacute thyroiditis exist in the early period of COVID‐19 vaccination, largely after mRNA vaccines. Here we report late onset thyroid disturbances and persistent health issues in patients of thyroid disorders after COVID‐19 vaccination. Seventy‐five patients with post COVID‐19 vaccination thyroid disturbances were identified. Among these, 41 had flare of underlying thyroid illness, majority occurring at a median time lag of 28.4 weeks since 2nd dose. Thirty‐one cases of new onset hypothyroidism and three of new onset hyperthyroidism were reported, with a median time lag respectively of 17.2 and 22.6 weeks since 2nd dose. Most cases occurred after ChAdOx1‐nCoV‐19, which was the commonest vaccine employed in mass roll out in India. Significant improvement was observed in majority, after a median follow up of 22–26 weeks. New onset health issues persisting for ≥4 weeks were reported in 37.3% and were common in individuals with history of COVID‐19 before vaccine. New onset metabolic, musculoskeletal, and reproductive disorders were the common health complaints. Active monitoring is warranted for late onset adverse events after COVID‐19 vaccines of all types. Larger studies with involvement of unvaccinated individuals are required to understand the incidence and causality of late onset thyroid disturbances after COVID‐19 vaccines. [ABSTRACT FROM AUTHOR]

A booster dose of a COVID-19 vaccine has been proven effective in restoring vaccine effectiveness and is currently recommended for use in some populations at risk of severe COVID-19 infection. Since sex differences in adverse events are significant in response to the vaccines, the safety of booster selection must be studied to avoid serious adverse events (SAE), such as life-threatening diseases. First, this study aimed to identify sex differences in SAE incidences using a prospective cohort design. Second, a nested unmatched case-control study was used to identify factors associated with reported SAE within 30 days after the booster shot. Multivariable logistic regression indicated the adjusted odds ratio by accounting for host and vaccine variables, thus, policy effects. The findings confirmed that SAE was rare and that age-sex-dominated disease classifications differed. Specific to SAE following the booster dose, we found that females aged 12–40 had a higher risk of being reported with SAE than males of the same age, while males over 50 had a higher risk than females. Other risk factors identified were the presence of metabolic syndrome and the use of certain vaccine brands. Mechanisms could be explained by individual host responses rather than the vaccines' direct effect. Therefore, SAE could be preventable by age-sex-specific vaccine selection, post-vaccination precautions, and early symptom detection. Future vaccine development should aim to limit host-specific reactogenicity for safety concerns. [ABSTRACT FROM AUTHOR]

Objective To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12–15%, area under the curve 0.67–0.69). Conclusion Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. Trial registration https://clinicaltrials.gov ; NCT02585258. [ABSTRACT FROM AUTHOR]

ImportanceMyocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Whilst the aetiology is still being investigated; there is evidence that genetic predisposition may be a risk factor for the development of myocarditis. Furthermore, hormones are thought to contribute to sex-specific differences in myocarditis, skewed toward a larger risk in adolescent males. Objective: This unique sibling case series may help highlight potential mechanisms and prognostic factors in the development of myocarditis following COVID-19 vaccination in adolescent males. In this context, twin and familial studies provide a unique epidemiological perspective to investigate the interplay between genetic predisposition and other factors. Participants: Observational case series of all siblings reported to SAEFVIC11 SAEFVIC: Surveillance of Adverse Events Following Vaccination in the Community. with chest pain following COVID-19 vaccinations in Victoria, Australia. Exposure: mRNA vaccination (Comirnaty BNT162b2 COVID-19 (Pfizer-BioNTech) and Spikevax mRNA-1273 (Moderna). Findings: Our case series comprises 6 young males; two sets of monozygotic twins and one set of fraternal brothers following reports of chest pain associated with COVID-19 mRNA vaccination. Five patients were diagnosed with myocarditis as per Brighton Collaboration Criteria (Level 2). The remaining sibling, who did not have myocarditis, was subsequently diagnosed with pubertal delay. Conclusions: Understanding the genetic and hormonal risk factors and aetiology for myocarditis associated with COVID-19 vaccines is paramount. Further evaluation of specific genetic targets or biomarkers is required to understand the implications of population vaccine policy, particularly for adolescent and young adult males at highest risk for this AESI.

Summary: Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

• We generated background incidence rates for 41 AESIs across a network of 10 European healthcare databases, which included a population of 63 million individuals. • We highlighted the importance of the nature of the event and the setting in which it is diagnosed, which should be captured by the data banks that are used to calculate rates, otherwise underestimation is likely. • The background incidence rates are used to monitor the safety of COVID-19 vaccines by the EMA, national health authorities and vaccine manufacturers. In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE. [ABSTRACT FROM AUTHOR]

Association between messenger RNA (mRNA) COVID-19 vaccines and myocarditis has aroused public concern over vaccine safety. The goal of this study was to compare the prognosis of this condition with viral infection–related myocarditis over 180 days. A territory-wide electronic public health care database in Hong Kong linked with population-based vaccination records was used to conduct a retrospective cohort study. Since the roll-out of BNT162b2 (Pfizer-BioNTech), patients aged ≥12 years hospitalized with myocarditis within 28 days after BNT162b2 vaccination were compared against viral infection–related myocarditis recorded before the pandemic (2000-2019), over a 180-day follow-up period (starting from diagnosis of myocarditis). All-cause mortality, heart failure, dilated cardiomyopathy, heart transplant, and postdischarge health care utilization were examined with Cox proportional hazards models. A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection–related myocarditis were identified. One case (1.0%) of dilated cardiomyopathy and 2 cases (1.9%) of heart failure were identified in the postvaccination group, compared with 28 (3.7%) and 93 (12.2%) in the viral infection–related myocarditis group, respectively. Adjusted analysis showed that the postvaccination myocarditis group had a 92% lower mortality risk (adjusted HR: 0.08; 95% CI: 0.01-0.57). No significant differences in other prognostic outcomes were seen. This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.

In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials. Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest. Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI −0.4 to 20.6 and −3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI –23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI −3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39). The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets. [ABSTRACT FROM AUTHOR]

Studies of fluoroquinolone (FQ) safety across indications show increased collagen/neurological adverse event (AE) risk, yet patients still receive FQs for uncomplicated urinary tract infections (uUTIs). This retrospective, cohort study investigated the risk of collagen/neurological AEs of special interest (AESIs) with short-term FQ use versus standard-of-care antibiotics (trimethoprim-sulfamethoxazole [SXT], nitrofurantoin [NTF]) among female outpatients with uUTIs. This study was conducted between December 2009 and 2019 using Optum's de-identified Clinformatics Data Mart Database. Adjusted absolute risks were calculated for composite/collagen/neurological AESIs (Kaplan-Meier cumulative hazards, after applying stabilized inverse probability of treatment weighting [sIPTW]). Adjusted hazard ratios were generated (sIPTW Cox proportional hazard modeling). Overall, 954,777 patients were included: FQ ( n = 386,537 [40.5%]); SXT ( n = 237,120 [24.8%]); NTF ( n = 314,585 [32.9%]). Adjusted absolute risk range for collagen/neurological AESIs was <1%-4.5%. The hazard (95% CI) of tendon rupture was 25% higher with FQ versus SXT (1.25 [1.00-1.57]; P = 0.0497). Patients receiving FQ had lower hazard of neurological (0.95 [0.93-0.97]; P < 0.0001), central nervous system (0.85 [0.80-0.89]; P < 0.0001), and peripheral nervous system (0.96 [0.93-0.98]; P = 0.0016) AESIs versus NTF. Following a short treatment duration, FQs were associated with increased risk of tendon rupture versus SXT and reduced risk (adjusted hazard ratios) of neurological AESI versus NTF. Individual patient risk and consequences for known uncommon, yet serious, AEs need to inform appropriate antibiotic choice in treating uUTIs. Patient profile, efficacy, microbiome impact, safety, and surveillance should inform antibiotic selection for uUTI management, in accordance with guidelines.

Although secukinumab has demonstrated high efficacy and favorable safety in moderate‐to‐severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real‐world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab‐induced AESI. More than 1077 patients (aged 18–74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug‐associated vasculitis (n = 8), and drug‐induced lupus erythematosus (n = 4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T‐cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment. [ABSTRACT FROM AUTHOR]

Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia. Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period. There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21). This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term. [ABSTRACT FROM AUTHOR]

Prior durvalumab (anti-PD-L1 agent) studies in platinum-refractory metastatic urothelial carcinoma evaluated a dose of 10 mg/kg administered every two weeks. The nonrandomised phase 3b STRONG study (NCT03084471) evaluated the safety and efficacy of fixed-dose durvalumab at a more convenient dosing schedule in a previously treated patient population, more similar to a real-world clinical setting. 867 patients with urothelial or nonurothelial urinary tract carcinoma (UTC) who progressed on or after platinum or nonplatinum chemotherapy were treated with durvalumab 1500 mg every four weeks; 87% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, and 13% had an ECOG PS of 2. The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary and exploratory end-points included overall survival (OS), objective response rate (ORR) and disease control rate (at six and 12 months) (DCR). AESIs of any grade were reported in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4–8.2) and ORR was 18% (95% CI: 14.8–20.6), with complete responses in 5% of patients and a DCR at six months of 19% (95% CI: 16.1–22.1). Fixed-dose durvalumab monotherapy every four weeks has an acceptable safety profile and yields durable clinical activity in previously chemotherapy-treated patients with UTC. Safety and efficacy are consistent with previous durvalumab studies and other anti-PD-1/PD-L1 agents in this setting. NCT03084471 https://clinicaltrials.gov/ct2/show/NCT03084471. [Display omitted] • STRONG, a phase 3b study, had a large population similar to a real-world setting. • Patients had previously treated metastatic urothelial or nonurothelial carcinoma. • Patients received a fixed dose of durvalumab 1500 mg intravenously every four weeks. • The primary end-point was adverse events of special interest. • Durvalumab had an acceptable safety profile and durable clinical activity. [ABSTRACT FROM AUTHOR]

Background In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV; Typbar-TCV). While no safety concerns were identified in pre- and postlicensure studies, WHO's Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July–August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world's first public sector TCV introduction. Per administrative reports, 113 420 children 9 months–14 years old received TCV. Methods We evaluated adverse events following immunization (AEFIs) using passive and active surveillance via (1) reports from the passive NMMC AEFI surveillance system, (2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days postvaccination, and (3) chart abstraction for adverse events of special interest (AESIs) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. Results We identified 222/113 420 (0.2%) vaccine recipients with AEFIs through the NMMC AEFI surveillance system: 211 (0.19%) experienced minor AEFIs, 2 (0.002%) severe, and 9 serious (0.008%). At 48 hours postvaccination, 1852/5605 (33%) caregivers reported ≥1 AEFI, including injection site pain (n = 1452, 26%), swelling (n = 419, 7.5%), and fever (n = 416, 7.4%). Of the 4728 interviews completed at 7 days postvaccination, the most reported AEFIs included fever (n = 200, 4%), pain (n = 52, 1%), and headache (n = 42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESIs were causally associated with TCV. Conclusions No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months–14 years old. [ABSTRACT FROM AUTHOR]

Introduction: In FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese patients with metastatic colorectal cancer (mCRC). However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known. The present analysis evaluated the safety profile and AESIs for fruquintinib in the FRESCO trial. Methods: In FRESCO, eligible Chinese patients were randomized (2:1) to receive fruquintinib (5 mg once daily for 3 weeks, followed by 1 week off in 28-day cycles) or placebo plus best supportive care. Treatment-related AESIs and time to first occurrence of AESIs were summarized. Treatment-related TEAEs by age, sex, and BMI were also summarized. Results: A total of 266 patients (95.7%) in the fruquintinib group and 97 (70.8%) in the placebo group had at least one treatment-related TEAE; the mean relative dose intensity was 92% and 98%, respectively. In the fruquintinib group, the most common (in > 40% of patients) treatment-related AESIs were hypertension (55.4%), palmar-plantar erythrodysesthesia syndrome [known as hand-foot skin reaction (HFSR)] (49.3%), and proteinuria (42.1%). The most common treatment-related grade ≥ 3 AESIs (≥ 3% of patients) were hypertension (21.2%), HFSR (10.8%), and proteinuria (3.2%); the median time to onset of these events was 10, 21, and 20 days, respectively. Subgroup analysis by age, sex, and BMI revealed that the frequencies of treatment-related TEAEs were similar across all subgroups, and were consistent with the overall safety profile of fruquintinib. Conclusions: The most common treatment-related grade ≥ 3 AEs were hypertension, HFSR, and proteinuria. The treatment-related TEAE profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population. Trial Registration: Clinical Trials identifier NCT02314819. [ABSTRACT FROM AUTHOR]

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs)., Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated., Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis., Discussion/conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab., Competing Interests: Masatoshi Kudo reports the following conflicts of interest: honoraria payment to self from Bayer, Chugai Pharmaceutical Co. Ltd., Eli Lilly, Eisai, and Takeda; research funding to institution from AbbVie, Chugai Pharmaceutical Co. Ltd., EA Pharma, Eisai, F. Hoffmann-La Roche Ltd, GE HealthCare, Gilead Sciences, Otsuka, Sumitomo Dainippon Pharma, Taiho, and Takeda; and Editor in Chief of Liver Cancer. Kaoru Tsuchiya reports the following conflicts of interest: advisory/consultancy fees to self from Chugai Pharmaceutical Co. Ltd. and Eisai; speakers bureau participation for Chugai Pharmaceutical Co. Ltd., Eisai, Eli Lilly, and Takeda; and research funding to institution from F. Hoffmann-La Roche Ltd. Yu-Yun Shao reports the following conflicts of interest: honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd, Ipsen, Merck, and Ono. Richard S. Finn reports the following conflicts of interest: consulting fees to self from AstraZeneca, Bayer, CStone Pharmaceuticals, Eisai, Eli Lilly, Exelixis, F. Hoffmann-La Roche Ltd., Hengrui, Merck, and Pfizer; research funding to institution from Adaptimmune, Bristol Myers Squibb, Eisai, Eli Lilly, Merck, Pfizer, and F. Hoffmann-La Roche Ltd.; and Editorial Board Member of Liver Cancer. Peter R. Galle reports the following conflicts of interest: consulting fees to self from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp & Dohme, and Sirtex Medical; honoraria payment to self from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp & Dohme, and Sirtex Medical; advisory fees to self from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp & Dohme, and Sirtex Medical; and research funding to institution from Bayer and F. Hoffmann-La Roche Ltd. Michel Ducreux reports the following conflicts of interest: honoraria, consulting fees, or advisory fees to self from Amgen, AstraZeneca, Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, Merck Serono, Pierre Fabre, and Servier; travel support from Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, Merck Sharp & Dohme, and Servier; speakers bureau participation for Amgen, Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, and Merck Serono; and research funding to institution from Bayer and F. Hoffmann-La Roche Ltd. Ann-Lii Cheng reports the following conflicts of interest: research funding to institution from F. Hoffmann-La Roche Ltd. Tatsuya Yamashita reports the following conflicts of interest: speakers bureau participation for Bayer and Chugai Pharmaceutical Co. Ltd. and research funding to institution from F. Hoffmann-La Roche Ltd. Hironori Koga reports the following conflicts of interest: research funding to institution from AbbVie, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo, and F. Hoffmann-La Roche Ltd. Ryosuke Take, Kyoko Yamada, Takashi Asakawa, and Yuki Nakagawa reports the following conflicts of interest: employment by Chugai Pharmaceutical Co. Ltd. Masafumi Ikeda reports the following conflicts of interest: honoraria to self from Bayer, Chugai Pharmaceutical Co. Ltd., Eisai, Eli Lilly, and Takeda; advisory/consulting fees to self from Chugai Pharmaceutical Co. Ltd., Eisai, Eli Lilly, Merck Sharp & Dohme, and Takeda; and research funding to institution from Bayer, Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme, and Takeda., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac., Methods: We conducted a self-controlled case series (SCCS) and a case-control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case-control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions., Findings: A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99-6.70] in 1-14 days and 2.50 (95%CI:1.43-4.38) in 15-28 days after first dose; 10.81 (95%CI:7.63-15.32) in 1-14 days and 2.95 (95%CI:1.82-4.78) in 15-28 days after second dose; 4.72 (95%CI:1.40-15.97) in 1-14 days after third dose. Consistent results were observed from the case-control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses., Interpretations: We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed., Funding: : This study was funded by Hong Kong Health Bureau (COVID19F01)., Competing Interests: FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. XL has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region; research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme, unrelated to this work. EYFW has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, and the Hong Kong Research Grants Council, outside the submitted work. CKHW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund; outside of the submitted work. EWYC reports honorarium from Hospital Authority; and grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, outside the submitted work. CSLC has received grants from the Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. All other authors declare no competing interests., (© 2023 The Author(s).)

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population., Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases., Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism., Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term., Funding: None., Competing Interests: EAV, AS, CB, RM, KH, AGS, GR, MJS, and PBR are employees of Janssen Research and Development LLC and shareholders of Johnson & Johnson (J&J) stock. Many data partners (including JMR, JMRA, MAM, MdW, LHJ, GB, PRR) on this project have received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The funding source had no role in writing the manuscript or the decision to submit it for publication. Odysseus Data Services, where SvS is employed, is a beneficiary of the mentioned IMI 2 JU project. DPA has received support from the EMA and Innovative Medicines Initiative. DPA's research group has received grant support from Amgen, Chesi-Taylor, Novartis, GSK, UCB Biopharma and J&J. DPA's department has received advisory/consultancy fees from AstraZeneca, Amgen, Astellas, J&J, and UCB Biopharma. DPA's department has received fees for speaker services from Amgen and UCB Biopharma. DPA's has other financial or non-financial interests in Janssen, on behalf of the IMI-funded EHDEN and European Medical Information Framework (EMIF) consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department that was open for external participants. TDS received financial support from the Institute de Salud Carlos Ill (ISCIII; Miguel Servet 2021: CP21/00023) which is co-funded by the European Union. The funding source had no role in writing the manuscript or the decision to submit it for publication. PRR, MdW, LHJ work for a research group who received/receives unconditional research grants from Chiesi, Amgen, UCB, J&J, European Medicines Agency (EMA), and IMI. GH provided funding for use of the CUIMC database and the OHDSI infrastructure. GH received support through a grant to Columbia University (NIH R01 LM006910). MAS receives grants from the US Department of Veterans Affairs within the scope of this work, and grants and contracts from the US National Institutes of Health, US Food & Drug Administration, and Janssen Research & Development outside the scope of this work. EPM receives salary support from the Department of Medicine at University of Calgary. EPM receives consulting fees from Janssen Research & Development for work that is outside the scope of the current study. FM's main employment is for Heliant d.o.o, an EHR provider in Serbia. JDP received salary support through the Universidad de Norte. DJD and ZC are full-time employees of CPRD, which provides contract research services for government and related healthcare authorities, and the pharmaceutical industry, including Janssen. FN holds some AstraZeneca shares and was employed there until 2019. RV, AJB, AP2, LD, and CH received partial funding for this work by the University of California Health System and its Center for Data-Driven Insights and Innovation. MGK received support for the manuscript via institutional (internal funding) only. AJB's research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor’s Office of Planning and Research, California Institute for Regenerative Medicine, L’Oréal, and Progenity. AJB receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. AJB is a co-founder and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche. AJB has received honoraria and travel reimbursement for invited talks from J&J, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, many academic institutions, medical or disease specific foundations and associations, and health systems. AJB is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, Vet24seven, and several other non-health related companies and mutual funds. DRM has grants or contracts from Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). FB has a leadership or fiduciary role as the program chair of j-ISBA., (© 2023 The Author(s).)

Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status. Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open. Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort. Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612). [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Lenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting., Patients and Methods: Patients had received ≥ 1 prior antimyeloma therapy; prior lenalidomide was excluded. Treatment was per investigator's routine practice. Adverse events were analyzed by incidence rates per 100 person-years to account for differences in observation length and treatment duration., Results: In total, 2150 patients initiated lenalidomide, and 1479 initiated any other antimyeloma therapy, predominately bortezomib (80.3%), which was primarily administered intravenously (74.3%). The incidence rate of neuropathy was lower with lenalidomide (10.5) than with bortezomib (78.9) or thalidomide (38.7). Lenalidomide also had a lower incidence rate of infections (68.7) versus bortezomib (95.9) and thalidomide (76.0). Conversely, the incidence rate of neutropenia was higher with lenalidomide (38.0) than with bortezomib (18.2) or thalidomide (25.7). The incidence rates of thrombocytopenia were 24.4, 40.4, and 14.4 with lenalidomide, bortezomib, and thalidomide, respectively., Conclusion: No new safety signals for lenalidomide were identified in this study, which is the largest prospective real-world European study of lenalidomide in patients with RRMM to date. These results confirm that the safety profile of lenalidomide plus dexamethasone in RRMM in a real-world setting is comparable to that reported in clinical trials., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)