Nanotoxicology. 2021 Jul 2:1-22. doi: 10.1080/17435390.2021.1943032. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.

PMID:34213984 | DOI:10.1080/17435390.2021.1943032

Aust Prescr. 2021 Jun;44(3):96-106. doi: 10.18773/austprescr.2021.015. Epub 2021 Jun 1.

ABSTRACT

People with alcohol-associated liver disease often take medicines to manage complications of liver disease and comorbidities. However, patients may be at increased risk of drug-related harm Assessing the severity of liver disease is fundamental to management, as disease staging (steatosis, early fibrosis, cirrhosis) affects medication safety and guides treatment While clinically significant pharmacokinetic and pharmacodynamic changes predominantly occur in cirrhosis, people with early alcohol-associated liver disease may still experience adverse events with potentially inappropriate medicines such as proton pump inhibitors, opioids and benzodiazepines Regular medication review is essential to ensure ongoing appropriateness and safety Alcoholic hepatitis and cirrhosis require specialist gastroenterology or hepatology management. However, general practitioners will remain the cornerstone of day-to-day medication management.

PMID:34211248 | PMC:PMC8236868 | DOI:10.18773/austprescr.2021.015

Drug Ther Bull. 2021 Jul 1:dtb-2021-000037. doi: 10.1136/dtb.2021.000037. Online ahead of print.

ABSTRACT

Overview of: Mahady SE, Margolis KL, Chan A, et al Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2021. 717-24.

PMID:34210661 | DOI:10.1136/dtb.2021.000037

Drug Ther Bull. 2021 Jul 1:dtb-2021-000036. doi: 10.1136/dtb.2021.000036. Online ahead of print.

ABSTRACT

Overview of: Tomlinson J, Cheong VL, Fylan B, et al Successful care transitions for older people: a systematic review and meta-analysis of the effects of interventions that support medication continuity. Age and Ageing 2020;49:558-69.

PMID:34210660 | DOI:10.1136/dtb.2021.000036

Vaccines (Basel). 2021 Jun 18;9(6):673. doi: 10.3390/vaccines9060673.

ABSTRACT

Recent reports of thrombosis following AstraZeneca COVID-19 vaccine in young females (<55 years-old) led to temporary suspension and urgent investigation by the European Medicines Agency (EMA) that concluded that vaccine benefits still outweigh its side effects (SEs). Therefore, this study aims to provide early independent evidence on the vaccine SEs' prevalence and their potential risk factors; a cross-sectional survey-based study was carried out between February and March 2021 in Germany and Czech Republic among healthcare workers who recently received the AstraZeneca COVID-19 vaccine. The study used a validated self-administered questionnaire composed of twenty-eight multiple-choice items covering demographic variables, medical anamneses, and local, systemic, oral, and skin related SEs of the vaccine. Out of the ninety-two included participants, 77.2% were females and 79.3% were from Germany. Their mean age was 35.37 ± 12.62 (19-64) years-old, 15.2% had chronic illnesses and 22.8% were receiving medical treatments. Overall, 94.6% of the participants reported at least one SE. The most common local SE was injection site pain (72.8%), and the most common systemic SEs were fatigue (73.9%), muscle pain (55.4%), chills (48.9%), feeling unwell (46.7%), nausea (45.7%), and headache (29.3%). The vast majority (91.9%) resolved within 1-3 days, and the below 35 years-old group was the least affected age group. The SEs' frequency was insignificantly higher in females and previously infected participants; the vaccine safety for the elderly was supported by the early findings of this study. Chronic illnesses and medical treatments were not associated with an increased risk of SE incidence and frequency. No blood disorder SEs were reported in our sample. Further independent studies are highly required to evaluate the safety of the AstraZeneca vaccine and to explore whether gender or previous infection could be associated with the vaccine SEs.

PMID:34207369 | DOI:10.3390/vaccines9060673

Antibiotics (Basel). 2021 Jun 22;10(7):757. doi: 10.3390/antibiotics10070757.

ABSTRACT

Resistance of Cutibacterium acnes to topical antibiotics historically used to treat acne (topical erythromycin and clindamycin and, more recently, topical azithromycin and clarithromycin) has been steadily increasing and new topical antibiotics are needed. Minocycline is a semisynthetic tetracycline-derived antibiotic currently used systemically to treat a wide range of infections caused by Gram-negative and Gram-positive bacteria. In addition to its antibiotic activity, minocycline possesses anti-inflammatory properties, such as the downregulation of proinflammatory cytokine production, suppression of neutrophil chemotaxis, activation of superoxide dismutase, and inhibition of phagocytosis, among others. These characteristics make minocycline a valuable agent for treatment of dermatological diseases such as acne vulgaris and papulopustular rosacea. However, more frequent or serious adverse effects have been observed upon the systemic administration of minocycline than with other tetracyclines. Examples of serious adverse effects include hypersensitivity syndrome reaction, drug-induced lupus, idiopathic intracranial hypertension, and other autoimmune syndromes that may cause death. Here, we review adverse effects and drug-drug interactions observed with oral administration of minocycline and contrast this with topical minocycline formulations recently approved or under development for effectively treating dermatological disorders with fewer adverse effects and less drug interaction.

PMID:34206485 | DOI:10.3390/antibiotics10070757

J Pers Med. 2021 Jun 17;11(6):565. doi: 10.3390/jpm11060565.

ABSTRACT

Induced pluripotent stem cell (iPSC)-derived cell products hold great promise as a potential cell source in personalized medicine. As concerns about the potential risk of graft-related severe adverse events, such as tumor formation from residual pluripotent cells, currently restrict their applicability, we established an optimized tool for therapeutic intervention that allows drug-controlled, specific and selective ablation of either iPSCs or the whole graft through genetic safety switches. To identify the best working system, different tools for genetic iPSC modification, promoters to express safety switches and different safety switches were combined. Suicide effects were slightly stronger when the suicide gene was delivered through lentiviral (LV) vectors compared to integration into the AAVS1 locus through TALEN technology. An optimized HSV-thymidine kinase and the inducible Caspase 9 both mediated drug-induced, efficient in vitro elimination of transgene-positive iPSCs. Choice of promoter allowed selective elimination of distinct populations within the graft: the hOct4 short response element restricted transgene expression to iPSCs, while the CAGs promoter ubiquitously drove expression in iPSCs and their progeny. Remarkably, both safety switches were able to prevent in vivo teratoma development and even effectively eliminated established teratomas formed by LV CAGs-transgenic iPSCs. These optimized tools to increase safety provide an important step towards clinical application of iPSC-derived transplants.

PMID:34204193 | DOI:10.3390/jpm11060565

J Clin Med. 2021 Jun 15;10(12):2629. doi: 10.3390/jcm10122629.

ABSTRACT

BACKGROUND: COVID-19 vaccine hesitancy is a serious threat to mass vaccination strategies that need to be accelerated currently in order to achieve a substantial level of community immunity. Independent (non-sponsored) studies have a great potential to enhance public confidence in vaccines and accelerate their uptake process.

METHODS: A nationwide cross-sectional study for the side effects (SE) of CoronaVac was carried out in February 2021 among Turkish healthcare workers who were recently vaccinated. The questionnaire inquired about local and systemic SEs that occurred in the short-term, within four weeks, following vaccination.

RESULTS: A total of 780 healthcare workers were included in this study; 62.5% of them experienced at least one SE. Injection site pain (41.5%) was the most common local SE, while fatigue (23.6%), headache (18.7%), muscle pain (11.2%) and joint pain (5.9%) were the common systemic SEs. Female healthcare workers (67.9%) were significantly more affected by local and systemic SEs than male colleagues (51.4%). Younger age, previous infection, and compromised health status (chronic illnesses and regular medicines uptake) can be associated with an increased risk of CoronaVac SEs; Conclusions: The independent research shows a higher prevalence of CoronaVac SEs than what is reported by phase I-III clinical trials. In general, the results of this study confirm the overall safety of CoronaVac and suggest potential risk factors for its SEs. Gender-based differences and SEs distribution among age groups are worth further investigation.

PMID:34203769 | DOI:10.3390/jcm10122629

Nutrients. 2021 Jun 7;13(6):1961. doi: 10.3390/nu13061961.

ABSTRACT

Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient's risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body's ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug-drug, drug-disease, drug-nutrient, and drug-food interactions can significantly affect the patient's nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug-nutrient and drug-food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.

PMID:34200493 | DOI:10.3390/nu13061961

Molecules. 2021 Jun 2;26(11):3351. doi: 10.3390/molecules26113351.

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray-Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.

PMID:34199466 | DOI:10.3390/molecules26113351

Hawaii J Health Soc Welf. 2021 Jun;80(6):129-133.

ABSTRACT

Although frequently prescribed, certain antibiotics such as trimethoprim-sulfamethoxazole carry the risk of a rare yet life-threatening adverse effect, termed drug-induced aseptic meningitis. Morbidity can be avoided if the medication is identified and discontinued. Patients in reported cases tend to be female and have an autoimmune disease or prior adverse reaction to the offending agent. As a rare and poorly characterized condition, the subset of patients using antibiotics at risk for aseptic meningitis remains unclear; hence, cataloging these adverse events remains critical for better elucidating the disease. Here, we report a 62-year-old man with psoriasis and no prior history of sulfa allergy, who presented with a sudden onset of fever, chills, vomiting, and muscle aches 5 hours after taking single doses of trimethoprim-sulfamethoxazole and ciprofloxacin. Common infectious causes were ruled out, and his medications were discontinued. Despite initial symptom resolution with discontinuation, the patient neurologically deteriorated over the next two days before eventually recovering with supportive care. This case highlights the variable presentation of drug-induced aseptic meningitis. In contrast to previous reports of drug-induced aseptic meningitis, our patient was male, older than the median age of 40 years, and did not have a prior adverse reaction to the antibiotic. Furthermore, to the best of our knowledge, we report a possible case of antibiotic-induced aseptic meningitis in a patient with psoriasis. Lastly, the case emphasizes not only the value of a thorough medication history but also the importance of recognizing that patients may deteriorate in the first 48 hours before resolution.

PMID:34195619 | PMC:PMC8237324

Drug Ther Bull. 2021 Jun 30:dtb-2021-000038. doi: 10.1136/dtb.2021.000038. Online ahead of print.

ABSTRACT

Overview of: Sharma V, Simpson SH, Samanani S, et al Concurrent use of opioids and benzodiazepine/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: a case cross-over study. BMJ Open 2020;10:e038692.

PMID:34193516 | DOI:10.1136/dtb.2021.000038

Drug Ther Bull. 2021 Jun 30:dtb-2021-000035. doi: 10.1136/dtb.2021.000035. Online ahead of print.

ABSTRACT

Review of: Horne AW, Vincent K, Hewitt CA, et al Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2020; 396:909-17.

PMID:34193515 | DOI:10.1136/dtb.2021.000035

Medicine (Baltimore). 2021 Jul 2;100(26):e26478. doi: 10.1097/MD.0000000000026478.

ABSTRACT

This study aims to evaluate the effect of dose titration for different oral antiepileptic medications among children with epilepsy in Riyadh, Saudi Arabia.A single-center prospective pilot, cohort study was undertaken at a tertiary hospital in Riyadh, Saudi Arabia. All medical records of pediatric patients below the age of 14 years of age who has been newly diagnosed with epilepsy by attending a medical specialist or on a new epileptic treatment plans were enrolled in the study.A total of 76 epileptic patients were screened for 3 months' period and 48 patients were included in this study. Out of the 48 patients, 31 patients followed the regular practice in the titration processes and 17 patients were in the British national formulary (BNF) guideline. Fifteen children who were on monotherapy of levetiracetam were in regular practice guideline experienced poor seizure control with a recorded number of seizure incidence (n = 10). The patient in regular practice guidelines using a combination therapy of phenytoin and levetiracetam were experiencing some behavioral disturbance and sedation effect. Seventeen patients followed in the BNF guideline who were on levetiracetam were experienced less adverse effect (n = 2) with no behavioral changes.The group who followed the regular practice found having a greater incidence of documented adverse effects compared to the patients following the BNF guideline. The titrating antiepileptic medication has a detrimental effect on the pediatric population as observed in this study.

PMID:34190172 | DOI:10.1097/MD.0000000000026478

Trials. 2021 Jun 29;22(1):419. doi: 10.1186/s13063-021-05343-0.

ABSTRACT

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information for developing harm profiles but current analysis practices to detect between-group differences are suboptimal. Drug trials routinely screen continuous clinical and biological data to monitor participant harm. These outcomes are regularly dichotomised into abnormal/normal values for analysis. Despite the simplicity gained for clinical interpretation, it is well established that dichotomising outcomes results in a considerable reduction in information and thus statistical power. We propose an automated procedure for the routine implementation of the distributional method for the dichotomisation of continuous outcomes proposed by Peacock and Sauzet, which retains the precision of the comparison of means.

METHODS: We explored the use of a distributional approach to compare differences in proportions based on the comparison of means which retains the power of the latter. We applied this approach to the screening of clinical and biological data as a means to detect 'signals' for potential adverse drug reactions (ADRs). Signals can then be followed-up in further confirmatory studies. Three distributional methods suitable for different types of distributions are described. We propose the use of an automated approach using the observed data to select the most appropriate distribution as an analysis strategy in a RCT setting for multiple continuous outcomes. We illustrate this approach using data from three RCTs assessing the efficacy of mepolizumab in asthma or COPD. Published reference ranges were used to define the proportions of participants with abnormal values for a subset of 10 blood tests. The between-group distributional and empirical differences in proportions were estimated for each blood test and compared.

RESULTS: Within trials, the distributions varied across the 10 outcomes demonstrating value in a practical approach to selecting the distributional method in the context of multiple adverse event outcomes. Across trials, there were three outcomes where the method chosen by the automated procedure varied for the same outcome. The distributional approach identified three signals (eosinophils, haematocrit, and haemoglobin) compared to only one when using the Fisher's exact test (eosinophils) and two identified by use of the 95% confidence interval for the difference in proportions (eosinophils and potassium).

CONCLUSION: When dichotomisation of continuous adverse event outcomes aids clinical interpretation, we advocate use of a distributional approach to retain statistical power. Methods are now easy to implement. Retaining information is especially valuable in the context of the analysis of adverse events in RCTs. The routine implementation of this automated approach requires further evaluation.

PMID:34187533 | DOI:10.1186/s13063-021-05343-0

Medicine (Baltimore). 2021 Jul 2;100(26):e26234. doi: 10.1097/MD.0000000000026234.

ABSTRACT

INTRODUCTION: Rifampicin is currently used to treat various bacterial infections, with the most significant application in the treatment of tuberculosis. Dose-independent side effects of the drug can lead to the development of various coagulation disorders, among which disseminated intravascular coagulation is the most dangerous. The mechanism of coagulopathy itself is multifactorial, but it is thought to be mediated by an immune response (formation of antigen-antibody complexes) and consequent damage to platelets and the vascular endothelium.

PATIENT CONCERNS: A 66-year-old woman, with numerous comorbidities including chronic renal failure, condition after implantation of a permanent pacemaker, and a positive blood culture for Staphylococcus aureus, presented with spontaneous bleeding in the muscle wall, and in the clinical picture of hemorrhagic shock.

DIAGNOSIS: Knowing the multifactorial mechanism of rifampicin-induced coagulopathy, possible factors were considered, such as infections, comorbidities, drug use and drug-drug interactions, pathological laboratory parameters, and coagulograms. Clinical presentation of abdominal pain and intra-abdominal mass, with laboratory verification of prolonged activated partial thromboplastin time and computed tomography-proven hematoma suspected of acute bleeding, redirects clinical suspicion of drug-induced coagulopathy.

INTERVENTIONS: By discontinuing rifapicin and administering vitamin K and fresh frozen plasma, normalization of laboratory coagulation parameters was achieved. Bleeding from the muscle wall required correction of acute anemia with red cell concentrates, surgical intervention, and additional antibiotic therapy for secondary infection of the operative wound.

OUTCOMES: At the end of 6 weeks of antibiotic (antistaphylococcal) therapy (due to the basic suspicion of possible infectious endocarditis), the normalization of inflammatory parameters occurred with a sterile control blood culture and a normal coagulogram.

CONCLUSION: Clinicians should be aware of the possible side effects of the administered drugs, especially taking into account the overall clinical picture of a patient, including comorbidities and possible drug interactions.

PMID:34190146 | DOI:10.1097/MD.0000000000026234

Clin Case Rep. 2021 Jun 22;9(6):e04227. doi: 10.1002/ccr3.4227. eCollection 2021 Jun.

ABSTRACT

Immunotherapy is an expanding area of cancer treatment with significant promise. Despite their efficacy, checkpoint inhibitors are associated with a number of immune-related adverse events; here, we described thrombocytopenia secondary todurvalumab.

PMID:34188921 | PMC:PMC8218317 | DOI:10.1002/ccr3.4227

Tob Use Insights. 2021 Jun 14;14:1179173X211016867. doi: 10.1177/1179173X211016867. eCollection 2021.

ABSTRACT

INTRODUCTION: Pharmacy staff are a trusted source of advice on the safe and appropriate use of medicines and devices. Retail pharmacies deliver smoking cessation services and sell e-cigarettes in the UK. This review asks 'what knowledge, experience and ability do staff have to support e-cigarette users to quit smoking'.

METHODS: A systematic literature search was undertaken drawn on predefined eligibility criteria and a comprehensive search strategy following the PRISMA guideline. Eligible papers reported survey-research published in English from 2015 to 2020. PubMed, Google Scholar, OVID, EMBASE and MEDLINE Databases were searched. No restrictions on study design or language were applied. Two reviewers independently screened for inclusion/exclusion and then extracted the relevant information from the articles for synthesis.

RESULTS: Of 12 potentially eligible full-text studies, 1 was a duplicate, 7 were excluded as per eligibility criteria. Four papers were finally included in this literature review. Two studies indicated that pharmacy staff are less confident in giving advice on e-cigarette use. Knowledge on the adverse effects of e-cigarettes compared to traditional smoking cessation aids remain unclear. In one study, 42% of community pharmacists did not believe that e-cigarettes could be used for smoking cessation. Three studies identified need for specific regulations and professional support. The overall certainty of the evidence is 'low' or 'very low', with moderate levels of bias.

CONCLUSION: Pharmacists may be well placed to implement e-cigarette smoking cessation interventions, but most practitioners lacked knowledge and ability to support these customers citing unclear risk of harm. Pharmacists felt secure in recommending traditional cessation tools. Further regulation, guidelines and training is needed. Findings may be less generalizable in countries where e-cigarettes are banned. Their extent of knowledge, experience and ability to support users of e-cigarettes within their community to quit smoking is lacking.

PMID:34188579 | PMC:PMC8209790 | DOI:10.1177/1179173X211016867

J Clin Pharmacol. 2021 Jun;61 Suppl 1:S152-S160. doi: 10.1002/jcph.1827.

ABSTRACT

The efficacy and safety of a drug is dose or exposure related, and both are used to assess the benefit-risk balance of a given drug and ultimately to decide on the specific drug license, including its dose and indication(s). Unfortunately, both efficacy and safety are much more difficult to establish in neonates, resulting in very few drugs licensed for use in this vulnerable population. This review will focus on dose-related adverse events in neonates. Besides the regulatory classification on seriousness, adverse event assessment includes aspects related to signal detection, causality, and severity. Disentangling confounders from truly dose-related adverse drug events remains a major challenge, as illustrated for drug-induced renal impairment, drug-induced liver injury, and neurodevelopmental outcome. Causality assessment, using either routine tools (Naranjo algorithm, World Health Organization's Uppsala Monitoring Center causality tool) or a Naranjo algorithm tailored to neonates, still does not sufficiently and reliably document causality in neonates. Finally, very recently, a first neonatal severity-grading tool for neonates has been developed. Following the development of advanced pharmacokinetic approaches and techniques to predict and assess drug exposure, additional efforts are needed to truly and fully assess dose adverse drug events. To further operationalize the recently developed tools on causality and severity, reference databases on a palette of biomarkers and outcome variables and their covariates are an obvious next step. These databases should subsequently be integrated in modeling efforts to truly explore safety outcome, including aspects associated with or caused by drug dose or exposure.

PMID:34185907 | DOI:10.1002/jcph.1827

Ophthalmic Surg Lasers Imaging Retina. 2021 Jun;52(6):327-335. doi: 10.3928/23258160-20210528-05. Epub 2021 Jun 1.

ABSTRACT

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of 1.0 mg risuteganib in subjects with nonexudative age-related macular degeneration (AMD).

PATIENTS AND METHODS: This was a phase 2a, prospective, double-masked, sham-controlled study. Eyes with nonexudative (dry) AMD and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/40 and 20/200 were included. Subjects were randomized to intravitreal 1.0 mg risuteganib or sham injection. At Week 16, subjects in the risuteganib group received a second 1.0-mg dose and the sham group crossed over to receive a dose of 1.0 mg risuteganib and were evaluated at Week 28. The primary endpoint was proportion of subjects with 8 letters ETDRS or more BCVA gain from baseline to Week 28 in the risuteganib group versus baseline to Week 12 for the sham group. BCVA was tested and subjects were observed for adverse events (AEs) every 4 weeks until completion of the study at 32 weeks.

RESULTS: Forty-five subjects (risuteganib, n = 29; sham, n = 16) were enrolled in the study, of whom 39 (risuteganib, n = 25; sham, n = 14) completed the study and were included in the per protocol efficacy analysis. At baseline, mean age was 78.8 and 75.9 years and mean BCVA was 67.1 and 64.4 letters in the sham and risuteganib groups, respectively. The primary endpoint was met by 48% of the risuteganib group at Week 28 and 7% of the sham group at Week 12 (P = .013). Of the risuteganib subjects, 20% gained 15 letters or more at Week 28, whereas no patients in the sham group at Week 12 achieved this visual acuity gain. The only ocular treatment-related treatment-emergent AE was vitreous floaters, which spontaneously recovered without sequelae. No drug-related serious AE was reported.

CONCLUSIONS: Risuteganib demonstrated significant BCVA improvement in patients with non-exudative AMD. No drug-related AEs were seen during a 32-week observation period. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:327-335.].

PMID:34185587 | DOI:10.3928/23258160-20210528-05