Post-marketing Clinical Trials Research Articles

Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of postmarketing spontaneous safety reports

ObjectivesThe ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. MethodsA retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. ResultsWe identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97−2.25)], stroke [n = 973, adj.ROR=1.25 (1.16−1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13−1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17−1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00–1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years. ConclusionIn this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.

The impacts of undetected nonadherence in phase II, III and post-marketing clinical trials: An overview.

This research aims to provide an overview of the consequences of undiagnosed nonadherence (noninitiation, suboptimal implementation, nonpersistence) in randomized clinical trials (RCTs). This research was conducted by combining a literature review and qualitative semistructured interviews with key opinion leaders. Based on this groundwork, the consequences of undiagnosed nonadherence in RCTs were summarized and reported in a figure. This study focused on phases II, III and post-marketing in ambulatory settings across a variety of therapeutic areas and indications. Various consequences of nonadherence in RCTs were investigated. In phase II, drug efficacy may be underestimated, variability in the outcomes may be high and a distorted picture of side effects could be reported, resulting in an uncertain impression of the investigational product's profile and complicating decision-making. The sponsor may need to increase the sample size of the upcoming phase III study to improve its power, representing additional costs, or even terminate the study. In phase III, similar phenomena may be observed, making demonstration of efficacy to the regulatory bodies more difficult. Lastly, after commercialization, a distortion in pharmacometrics may occur: the drug may underperform, prescriptions may be refilled less often than expected or extra expenses may be incurred by the payers. This can result in post-marketing dose reduction, new competitors coming into the market and, eventually, product withdrawal. This research highlighted the many potential adverse consequences of undiagnosed nonadherence in RCTs, including additional costs. Collecting accurate data appeared to be crucial for decision-making throughout the drug development process.

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer's Disease.

Alzheimer's disease is the most common form of dementia and includes cognitive, personality, and behavioral changes. The 2024 report from the Alzheimer's Association estimated that 6.9 million adults >65 years in the US are currently living with Alzheimer's disease. Modeling studies predict that this number will double by 2050, and associated healthcare costs will reach $1 trillion. In June 2021, regulatory approval of aducanumab, a humanized recombinant monoclonal antibody to amyloid ß, initially raised expectations for improved disease-modifying therapy. However, in February 2024, production of aducanumab and a post-marketing clinical trial ceased in the US due to the costs and limitations of aducanumab therapy. In March 2024, biobank data identified significant modifiable risk factors for Alzheimer's disease, including diabetes mellitus, exposure to nitrogen dioxide (a proxy for air pollution), and the frequency of alcohol intake. Therefore, modification of identifiable risk factors, combined with testing for disease-susceptibility genes, could be the most effective approach to reduce the incidence. This article aims to review the current status of disease-modifying therapies and prevention of Alzheimer's disease.

Safety of Secukinumab from 1Million Patient-Years of Exposure: Experience from Post-Marketing Setting and Clinical Trials.

Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25June2022. Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications. Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY). Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.

Therapy adherence, safety and efficacy of rivaroxaban in prevention of venous thromboembolism in patients with hip or knee endoprosthesis.

Rivaroxaban is a potent, selective direct inhibitor of factor Xa. The aim of this study was to evaluate the therapy adherence, safety and efficacy of rivaroxaban therapy in reducing the risk of venous thromboembolism in patients undergoing elective hip or knee replacement. The prospective, post-marketing clinical trial was conducted on adult patients after knee or hip endoprosthesis. Data were collected at the baseline and three control visits (five days, a month and three months after the baseline). Morisky Medication Adherence Scale (MMAS-8) was used for evaluation of therapy adherence. The study included 60 patients who received rivaroxaban therapy in a dose of 10mg once a day. A low adherence to the drug was observed in 15% patients. All patients had an average MMAS-8 score in the range of high adherence 0.65 ± 0.90. Symptomatic venous thromboembolism was observed in two patients with numerous risk factors. No major bleeding was recorded during entire follow-up period. During the five-day postoperative in-hospital follow-up, signs of wound complications were recorded in 8 (13.3%) patients, and 4 (6.7%) of them underwent surgical revision of the wound. Generally, there was high adherence to rivaroxaban therapy, but low adherence was present in 15% of patients. Rivaroxaban showed good safety and efficacy. However, high proportion of wound complications and patients needing surgical revision of the wound should be further evaluated through larger studies.

Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non-orphan drugs approved by the FDA.

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food-drug interaction, drug-drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug-drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.

Advanced delivery of leuprorelin acetate for the treatment of prostatic cancer

ABSTRACT Introduction Androgen-deprivation therapy (ADT) is the main therapy for patients with advanced and metastatic prostate cancer (PCa) and, in combination with radiotherapy, for patients with localized high-risk PCa. Due to its favorable tolerability among different treatments available for ADT, leuprorelin acetate is well established as the leading luteinizing hormone-releasing hormone (LHRH) analog. The development of second-generation leuprorelin acetate (LA) depot formulation (Eligard®, Recordati S.p.A) allowed a consistent and controlled release of leuprorelin between injections and a more efficient reduction of testosterone levels with respect to conventional LHRH agonists. Areas covered This work provides a summary of the biological and clinical rationale for using LA to manage PCa and presents the current evidence about the therapeutic activity of the LA gel depot formulation, used as an advanced leuprorelin acetate delivery method. Expert opinion Results of the registration studies and post-marketing clinical trials demonstrate that the LA gel depot provides long-term efficacy in the clinical practice and a good degree of tolerability. Overall, collected data suggest that the LA gel depot can represent the ADT reference therapy in advanced PCa.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Regulatory aspects of clinical trials in case of emergency

The article deals with aprocedure of clinical trial of medical product for human use and describes regulatory aspects of а clinical trial in case of emergency, including the COVID-19 pandemic, analyses the grounds and conditions of studding properties of medical product, passed the state registration, for off-label use, without post-marketing clinical trial (low-interventional study). An assessment is made of the streamlined procedure of the registration of medical products, referring for the prophylactic and treatment of the diseases incase of emergency, andit is concluded about necessity ofextension this proceduretomedical products, which can be used for the treatment of other types of diseases.

Vaccinal chronicity: immunotherapy, primary care, and the temporal remaking of lung cancer’s patienthood in Cuba

The Cuban biotechnology industry is producing cancer immunotherapy, in particular, therapeutic vaccines that actively stimulate the immune system to stabilise the tumour. These products aim to transform metastatic malignancies into a chronic disease. Since 2010, this therapeutic concept has been integrated within a public health experiment, consisting of the large distribution of immunotherapies, including in primary healthcare centres, to enhance access and assess its effectiveness on a wider population of patients. Such experimental intervention, consisting of post-marketing clinical trials, has focused only on lung cancer, one of the most widespread and lethal cancers on the island. Combining interviews with ethnographic observations focusing on care performed by professionals, patients, and their relatives, this paper analyses the experience of lung cancer chronicity under this type of immunotherapy in Cuba. It shows how a certain form of continuity is made between prophylactic and therapeutic vaccination to shape a new temporality of cancer care, through the integration within primary care, constant access to biotechnology, and multiple care practices directed to strengthen the immunotherapy’s efficacy. If vaccinal chronicity remains fragile due to its experimental dimension and the fact that long-term survivorship is still an exceptional phenomenon, lung cancer patienthood is deeply transformed through a shared effort of the people and the state to provide more stable, meaningful, and inclusive care.

Overview of Phase IV Clinical Trials Targeting COVID-19: Status Report of Studies Registered on the ClinicalTrials.gov Platform

Introduction: Phase IV trials evaluate drugs' efficacy, safety, and tolerability in a real-world setting, which may provide evidence related to the safety of approved drugs. This study aimed to characterize the phase IV clinical trials registered at ClinicalTrials.gov targeting COVID-19 and reflect on future needs for post-marketing clinical trials. Methods: A descriptive cross-sectional study was performed in the ClinitalTrials.gov database with phase IV clinical trials addressed to COVID-19. The search was carried out on March 23rd, 2021, considering search filters for this disease. Results: A total of 146 protocols were retrieved through a structured search. The results showed the need to promote new, blinded, and larger sample-size phase IV clinical trials. 93.9% of the clinical trials were funded by individuals, universities, and organizations (category "other" funders), and 56.8% were open-label. America and Europe played a more critical role in phase IV clinical trials, with the former leading with 58 trials spread across five countries and the latter with 38 trials in 17 countries. More than two-thirds of the trials (69.8%) included 500 participants. Conclusions: For the observed period, phase IV clinical trials registered in the ClinicalTrials.gov were dominated by short-term follow-up, open-label designs, small sample sizes, funded mainly by individuals, universities, and organizations, and centered mainly in America and Europe. The methodological features of future studies should be emphasized, namely adequate sample sizes, for which appropriate funding for the implementation of these studies is paramount.

THE SYSTEMIC STUDY OF VARIOUS VACCINES IN TERM OF CURRENT STATUS OF CLINICAL TRIAL, SAFETY AND EFFECTIVENESS OF COVID VACCINE

Industries leading the experiment and clinical trial of various vaccines to approve effectiveness and safety on humans. Several of them were documentation for a patent, authorization of clinical trial and marketing. In the review study, we provide an overview of Covid-19, types of vaccine and mechanism of action. Consider the reference of the mechanism of actions such as an inactivated vaccine, vector vaccines, DNA and RNA based vaccine and antiviral drugs already entered in (Phase II and III) clinical trials. The systemic study quantified a summary of various vaccines in the form of the present status of clinical trial, safety and effectiveness according to ICH E6 (R2) guidelines. Due to leading adverse interaction with their toxicity study, the inventor may face challenges during the post-marketing clinical trial. The genuine information allows upcoming scientists to improve the quality, and minimize the adverse effects and avoid resistance power for developing newer drugs.

Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China.

Pharmacometrics is an emerging science that interprets drug, disease, and trial information in a mathematical fashion to inform and facilitate efficient drug development and/or regulatory decisions. Pharmacometrics study is increasingly adopted in the regulatory review of new antimicrobial agents. We summarized the 31 antimicrobial agents approved by the US Food and Drug Administration (FDA) and the 26 antimicrobial agents approved by European Medicines Agency (EMA) from January 2001 to May 2019. We also reviewed recent examples of utilizing pharmacometrics to support antimicrobial agent’s registration in China, including modeling and simulation methods, effects of internal/external factors on pharmacokinetic (PK) parameters, safety and efficacy evaluation in terms of exposure‐response analysis, refinement of the wording of product labeling and package leaflet, and possible postmarketing clinical trial. Ongoing communication among regulator, academia, and industry regarding pharmacometrics is encouraged to streamline and facilitate the development of new antimicrobial agents. The industry can maximize its benefit in drug development through continued pharmacometrics education/training.

Medical Affairs in Pharmaceutical Companies and Related Pharmaceutical Regulations in Japan.

Medical affairs has received a lot of attention in recent years in Japan, but it is also often misunderstood or poorly understood in the healthcare industry in Japan. In the United States, the function of medical affairs has been established for a long time, whereas its history in Japan is relatively short. Many scandals in clinical trials occurred with inappropriate relationship between medical doctors and the sales departments of pharmaceutical companies from 2012. These incidents undermined confidence in clinical trials in Japan and triggered the enforced separation of sales departments from the conduct of post-marketing clinical trials and evidence generation. There have been growing compliance issues identified in marketing and sales practices, and off-label promotion is also becoming an issue in Japan. These issues resulted in the establishment of independent medical affairs departments from sales departments in pharmaceutical companies operating in Japan. Due to the short history of medical affairs in Japan, the roles and responsibilities vary between companies in Japan. Medical affairs departments aim to fulfill unmet medical needs through the generation of scientific evidence and to deliver scientific value to key stakeholders and patients. People working in medical affairs need to engage in scientific exchange activities with key opinion leaders independent of sales departments. Through these activities, medical affairs ensures that patients receive optimal medical care. Medical affairs in Japan is still developing, and its roles, responsibilities, and functions are improving. This article covers the history of medical affairs in Japan and the current status and future perspectives of medical affairs in Japan.

COVID-19 Vaccines: Systematic review

World facing pandemic challenges of SARS-Co-2 (Severe Acute Respiratory Syndrome Corona Virus 2). Tyrrell and Bynoe identified first strain of human corona virus in 1965. Infection was originated from Wuhan city of China on November 2019. Virus officially named as COVID-19 which causes respiratory tract infections in humans. Preliminary symptoms like chest pain with difficulty in breathing, reduced in systemic oxygen level, cough and fever. At present, the majority of the pharmaceutical companies were in race to developing antiviral drug and vaccines against COVID-19. Industries conducting the experiment and clinical trial of various vaccines to ensure effectiveness and safety on human. Several of them were documentation for patent, authorization of clinical trial and marketing. We provide an overview of Covid-19 history, types of vaccine and mechanism of actions, current future therapeutic drugs and patents. Relative with the mechanism of actions such as inactivated vaccine, vector vaccines, DNA and RNA based vaccine and antiviral drugs already entered in (Phase II and III) clinical trials. The systemic study specified brief summary of various vaccines. Current status of clinical trial, safety and effectiveness according to ICH guidelines. A major adverse interaction with their toxicity study. The information of approved which give opportunity for upcoming scientist to improve the quality, and minimize the adverse effects. Scientist may face challenges during the post marketing clinical trial. This pandemic has provided various scopes for researchers to develop vaccine and antiviral drugs.

Safety, immunogenicity of lyophilized purified vero cell cultured rabies vaccine administered in Zagreb and Essen regimen in post-exposure subjects: A post-marketing, parallel control clinical trial

ABSTRACT To compare the safety and immunogenicity of lyophilized PVRV under Zagreb and Essen regimen. A post-marketing parallel control clinical trial was conducted. Totally 240 subjects were assigned to two groups randomly, immunized with lyophilized PVRV under Zagreb and Essen schedule. Solicited adverse events were observed after each dose and unsolicited adverse events were collected. Serum samples were collected on days 0, 7, 14, 42, 180 and 365 to be used to determine immunogenicity level. No severe adverse events (SAE) were observed. The incidence of adverse events under Zagreb and Essen were similar and there was no significant difference between the two groups and within all age groups. Fever and pain were the most frequently reported systemic and local adverse events (AEs) respectively. There were no differences in the GMT and the positive seroconversion rate between these two groups. All participants in the Zagreb group obtained protective effect on day 14, while 99.16% of the subjects obtained in the Essen group. Both groups showed similar enduring immunity. Immunizations under Zagreb and Essen regimens showed similar safety and immunogenicity. For lyophilized PVRV, Zagreb was non-inferior to Essen to patients of all age groups.

Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients.

In 2016, biosimilar enoxaparin (Inhixa®, Techdow) was introduced in European markets with the same indications as branded enoxaparin (Clexane®, Sanofi). Its use is constantly increasing in clinical practice, however, little information from post-marketing clinical trials is available on its safety and effectiveness. We conducted an observational, retrospective study to assess the safety and effectiveness of Inhixa in preventing venous thromboembolism (VTE) in medically ill patients and in patients undergoing major abdominal surgery. We then compared our results with the incidence of symptomatic VTE and bleeding events during treatment with Clexane by pooling the results of clinical studies carried out in the same settings. We enrolled 381 patients, 189 admitted to a Medical Department and 192 to a Surgical Department from two single institutions. The incidence of major bleeding events was 1.8% globally (95% IC 0.7-3.8), 1.6% in medical patients (95% IC 0.3-4.6) and 2.1% in surgical patients (95% IC 0.6-5.3). VTE rate was 0.5% in the whole population (95% IC 0.1-1.9) and 0.5% (95% IC 0.01-2.9) in each group, respectively. The pooled estimate of the incidence of major bleeding with Clexane was 0.5% (IC 95%: 0.2-1.1) in medical patients and 2.6% (IC 95% 1.3-5.1) in surgical patients. The incidence of thrombotic events was 0.6% (IC 95%: 0.2-1.8) and 0.7% (CI95% 0.3-1.6), respectively. The incidence of bleeding and thrombosis in medical and surgical patients receiving Inhixa was low suggesting biosimilar enoxaparin is a valid alternative to branded enoxaparin.

Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial

BackgroundThere have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment. MethodsThis was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions. ResultsThe mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity. ConclusionsJC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.

Parkinson's Drug Doesn't Increase Prostate Cancer Risk.

The Food and Drug Administration (FDA) has determined that entacapone, used in the management of Parkinson's disease, does not increase the risk of prostate cancer or death from prostate cancer.The decision was based on an analysis of data from a postmarketing clinical trial conducted by the drug manufacturer and an FDA review of data from the Department of Veterans Affairs.

Ocular adverse events with immune checkpoint inhibitors

PurposeTo quantify the risk of ocular adverse events with immune checkpoint inhibitors (ICIs) as reported to the Food and Drug Administration (FDA). MethodsDisproportionality analysis using data from U.S. FDA's Adverse Events Reporting System (FAERS) database 2003 to 2018. Data from pharmaceutical manufacturers, healthcare providers, consumers in the U.S., and post-marketing clinical trial reports from U.S. and non-U.S. studies. All cases of uveitis, dry eye syndrome, ocular myasthenia and eye inflammation with use of the following ICIs: atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab and pembrolizumab. Reported odds ratios (RORs) and corresponding 95% confidence intervals (CIs) were computed for all drugs as a group or as individual agents. ResultsWe identified 113 ocular adverse events for all ICIs of interest including uveitis, dry eye, ocular myasthenia and eye inflammation. Nivolumab had the highest number of adverse events (N = 68) associated with use of the ICI. Nivolumab had the highest association with ocular myasthenia [ROR = 22.82, 95% CI (7.18–72.50)] followed by pembrolizumab [ROR = 20.17, 95% CI (2.80–145.20)]. Among all ICIs approved in North America, atezolizumab had the highest association with eye inflammation [ROR = 18.89, 95% CI (6.07–58.81)] and ipilmumab had the highest association with uveitis [ROR = 10.54, 95% CI (7.30–15.22)]. ConclusionThe results of this disproportionality analysis suggest use of ICIs is associated with an increase risk for ocular adverse reactions. Future epidemiologic studies are needed to better quantify these adverse events.