Arch Dermatol Res. 2024 Apr 25;316(5):133. doi: 10.1007/s00403-024-02868-7.

ABSTRACT

INTRODUCTION: Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited.

MATERIALS AND METHODS: An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab.

RESULTS: At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis.

CONCLUSION: Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.

PMID:38662223 | DOI:10.1007/s00403-024-02868-7

Glomerular Dis. 2024 Apr 2;4(1):84-90. doi: 10.1159/000538492. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: Alemtuzumab, a humanized monoclonal antibody indicated for the treatment of adult patients with active relapsing-remitting multiple sclerosis (MS), has been associated with increased risk of autoimmune adverse events, including thyroid disorders, immune thrombocytopenia, and renal diseases. Renal immune-mediated adverse events, which have been reported in 0.3% of patients treated with alemtuzumab in MS clinical trials, typically occur within 39 months after the last drug administration. However, no consensus has been reached regarding the management of patients who develop glomerulonephritis after treatment with alemtuzumab.

CASE PRESENTATION: We report the cases of two young adults with MS who developed biopsy-proven severe glomerulonephritis after alemtuzumab treatment. Both patients, including a 32-year-old female patient who developed membranous nephropathy and a 31-year-old male who developed drug-induced podocytopathy, were treated successfully with the calcineurin inhibitor tacrolimus followed by the anti-CD20 antibody rituximab.

CONCLUSION: Regular renal function monitoring is required in patients who may rarely develop glomerulonephritis following treatment with alemtuzumab. There is no clear consensus on case management. In both cases, immunosuppressive therapy, which was necessary due to disease severity, resulted in successful remission, highlighting the potential utility of this approach.

PMID:38660579 | PMC:PMC11042795 | DOI:10.1159/000538492

Front Neurosci. 2024 Apr 10;18:1373375. doi: 10.3389/fnins.2024.1373375. eCollection 2024.

ABSTRACT

OBJECTIVE: To observe the efficacy and safety of pelvic floor magnetic stimulation (PFMS) combined with mirabegron in female patients with refractory overactive bladder (OAB) symptoms.

PATIENTS AND METHODS: A total of 160 female patients with refractory OAB symptoms were prospectively randomized into two groups. Eighty cases in the combination group accepted PFMS and mirabegron therapy and 80 cases as control only accepted mirabegron therapy (The clinical trial registry number: ChiCTR2200070171). The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQol), symptom bother score and OABSS between two groups were compared at the 1st, 2nd and 4th week ends.

RESULTS: All of 160 patients were randomly assigned to two groups, of which 80 patients were included in the combination group and 80 in the mirabegron group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week and the 4th week after combination treatment were significantly lower than those in the mirabegron group (p < 0.05). The incidence of drug-related adverse events between two groups was similar, and there was no statistically significant difference (p > 0.05). With respect to secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the mirabegron group between the 2nd week and the 4th week (p < 0.05). This was consistent with the primary outcome. Meanwhile, from the second to fourth week, the OAB-q symptom bother score and OABSS in the combination group were both lower than in the mirabegron group (p < 0.05).

CONCLUSION: Combination therapy of PFMS and mirabegron demonstrated significant improvements over mirabegron monotherapy in reducing refractory OAB symptoms for female patients, and providing a higher quality of life without increasing bothersome adverse effects.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, ChiCTR-INR-22013524.

PMID:38660220 | PMC:PMC11040079 | DOI:10.3389/fnins.2024.1373375

Cephalalgia. 2024 Apr;44(4):3331024241232944. doi: 10.1177/03331024241232944.

ABSTRACT

BACKGROUND: The present study evaluated the long-term safety and tolerability of rimegepant, an orally administered small molecule calcitonin gene-related peptide receptor antagonist, in people with migraine.

METHODS: This multicenter, long-term, open-label safety study included adults (≥18 years) with ≥1 year history of migraine who were sequentially enrolled into three groups: participants in the first two groups had either 2-8 or 9-14 moderate to severe migraine attacks per month by history and treated as needed (pro re nata [PRN]) with one rimegepant 75 mg oral tablet up to once per calendar day for 52 weeks (PRN 2-8 and PRN 9-14); a third group, included to collect safety data during higher-frequency dosing, had 4-14 moderate to severe migraine attacks per month by history and who took one rimegepant tablet every other day as scheduled dosing plus PRN dosing of one rimegepant tablet for migraine attacks of any severity on nonscheduled dosing days for 12 weeks (every other day (EOD) + PRN).

RESULTS: Overall, 1800 participants self-administered rimegepant (PRN 2-8: n = 1033; PRN 9-14: n = 481; EOD + PRN: n = 286). The most common on-treatment adverse events (AEs) were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%) and sinusitis (5.1%). Most AEs were mild or moderate and considered unrelated to rimegepant. Serious AEs considered possibly (n = 1) or unlikely (n = 9) related to rimegepant were reported in ten (0.6%) participants. No signal of drug-induced liver injury because of rimegepant was identified.

CONCLUSIONS: Rimegepant 75 mg up to once per day as EOD + PRN for 12 weeks or PRN for up to 52 weeks was safe and well tolerated. No signal of hepatotoxicity, potential drug abuse, or medication-overuse headache was identified.Trial registration: Clinicaltrials.gov: NCT03266588.

PMID:38659334 | DOI:10.1177/03331024241232944

Clin Drug Investig. 2024 Apr 24. doi: 10.1007/s40261-024-01357-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: BI 1358894, a novel small-molecule inhibitor of transient receptor potential canonical ion channels, is under development for treatment of major depressive disorder. Phase I trials assessing the safety and pharmacokinetics of BI 1358894 in Caucasian male healthy volunteers (HVs) have been performed. This Phase I, double-blind, placebo-controlled, parallel-group trial assessed the safety, tolerability and pharmacokinetics of BI 1358894 in Japanese male HVs.

METHODS: Male HVs were randomized to receive oral BI 1358894 (n = 18) or placebo (n = 6) after a high-fat, high-calorie meal within three dose groups (50 mg, 100 mg, 200 mg), administered sequentially in dose-ascending order. The primary endpoint was number of HVs with drug-related adverse events (DRAEs). Secondary endpoints were the pharmacokinetic parameters of BI 1358894.

RESULTS: Overall, 24 male HVs entered the trial [mean (standard deviation) age: 30.0 (7.6) years]. DRAEs occurred in 3/18 HVs (BI 1358894 100 mg group: one HV experienced dizziness and headache; BI 1358894 200 mg group: one HV experienced headache, another reported sleep disorder). BI 1358894 exposure increased dose dependently and proportionally, peaking 4-6 h after administration before declining in a multiphasic manner with a terminal elimination half-life of ~70 h in the 50 mg and 100 mg dose groups, and 203 h in the 200 mg dose group.

CONCLUSION: BI 1358894 was well tolerated with a favorable pharmacokinetic profile in Japanese male HVs, similar to findings from a previous study in Caucasian male HVs.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT03875001; 08-Mar-2019).

PMID:38656736 | DOI:10.1007/s40261-024-01357-z

J Viral Hepat. 2024 Apr 23. doi: 10.1111/jvh.13946. Online ahead of print.

ABSTRACT

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (n = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1-2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3-4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, n = 16; AE [deemed unelated to GLE/PIB], n = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.

PMID:38654438 | DOI:10.1111/jvh.13946

Eur J Cancer. 2024 May;203:114028. doi: 10.1016/j.ejca.2024.114028. Epub 2024 Mar 27.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICI) induce adverse events (irAEs) that do not respond to steroids, i.e. steroid-refractory (sr) irAEs, and irAEs in which steroids cannot be tapered, i.e. steroid-dependent (sd) irAEs, in about 10% of cases. An evidence-based analysis of the effectiveness of second-line immunosuppressive agents with regard to irAE and tumor control is lacking.

METHODS: The international web-based Side Effect Registry Immuno-Oncology (SERIO; http://serio-registry.org) is a collaborative initiative with the Paul-Ehrlich-Institute to document rare, severe, complex or therapy-refractory immunotherapy-induced side effects. The registry was queried on August 1, 2023 for cases of irAEs which were treated with second-line therapies.

RESULTS: From a total of 1330 cases, 217 patients (16.3%) received 249 second-line therapies. A total of 19 different second-line therapies were employed, including TNF-alpha antagonists (46.5%), intravenous immunoglobulins (IVIG; 19.1%), mycophenolate mofetil (15.9%), and methotrexate (3.6%). Therapy choices were determined by the type of irAE. The time to onset of sr-/sd-irAEs after ICI initiation did not consistently differ from steroid-responsive irAEs. While 74.3% of sr-/sd-irAEs resolved and 13.1% had improved, 4.3% persisted, 3.9% resulted in permanent sequelae, and 4.3% in death with ongoing symptoms. Infliximab exhibited potential for earlier symptom improvement compared to mycophenolate mofetil or IVIG. Tumor response in patients with second-line treated sd-/sr-irAE was similar to patients with irAEs treated with steroids only.

CONCLUSION: Several second-line therapies are effective against sr-/sd-irAEs, the second-line therapies show no clear negative impact on tumor response, and infliximab shows potential for faster improvement of symptoms. However, prospective comparative data are needed.

PMID:38652976 | DOI:10.1016/j.ejca.2024.114028

Clin Transl Sci. 2024 Apr;17(4):e13803. doi: 10.1111/cts.13803.

ABSTRACT

Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA. We retrospectively analyzed 37 DSCs of 41 adverse drug reactions (ADRs) for 33 drugs in Japan from 1997 to 2022. Most DSCs were related to non-oncology drugs (30/37, 81.1%), and the median (interquartile range) time from approval to DSC issuance was 19 (10-51) months. Notably, the regulatory review reports and the latest labels before DSC issuance did not describe 16/28 (57.1%) and 12/37 (32.4%) of the ADRs related to DSCs, respectively. Most DSCs resulted in label revisions (36/37, 97.3%) and seven drugs were eventually withdrawn. Some DSC characteristics are similar among the PMDA/MHLW, the FDA, and the EMA; however, the number, contents, and range of new safety issues addressed by DSCs differ among the three jurisdictions. Our study emphasized the importance of continuous efforts to gather postmarket drug safety information because substantial ADRs that led to DSCs were recognized after approval and were associated with critical label revisions and withdrawals. Future studies are required to address global challenges for regulatory harmonization of safety-related regulatory actions.

PMID:38651283 | PMC:PMC11036129 | DOI:10.1111/cts.13803

Acta Oncol. 2024 Apr 21;63:213-219. doi: 10.2340/1651-226X.2024.24179.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited.

AIMS: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients.

METHODS AND RESULTS: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed.

INTERPRETATION: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

PMID:38647024 | DOI:10.2340/1651-226X.2024.24179

Expert Opin Pharmacother. 2024 Apr 22. doi: 10.1080/14656566.2024.2346268. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute kidney injury (AKI) frequently develops in patients receiving cancer therapy and requires a wide differential diagnosis due to possible role of unique cancer and drug-related factors, in addition to common pre- and post-renal causes. Rapid development of new molecular targeted anti-cancer drugs and immunotherapies has opened unprecedented possibilities of treatment at the price of an increased spectrum of renal side effects.

AREAS COVERED: The present review aims at providing a state-of-the-art picture of AKI in cancer patient (PubMed and Embase libraries were searched from inception to January 2024), with a focus on differential diagnosis and management of diverse clinical settings. Reports of parenchymal AKI due to glomerular, microvascular, tubular and interstitial damage have been constantly increasing. Complex electrolyte and acid-base disorders can coexist. The role of renal biopsy and possible therapeutic approaches are also discussed.

EXPERT OPINION: Onconephrology has become an important subspecialty of clinical nephrology, requiring constantly updated skills and a high degree of interdisciplinary integration to tackle diagnostic challenges and even therapeutic and ethical dilemmas. Integrated onconephrological guidelines and availability of biomarkers may provide new tools for management of this unique type of patients in the near future.

PMID:38646905 | DOI:10.1080/14656566.2024.2346268

Front Immunol. 2024 Apr 5;15:1387465. doi: 10.3389/fimmu.2024.1387465. eCollection 2024.

ABSTRACT

BACKGROUND: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented.

METHODS: This case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas.

RESULTS: All six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab.

CONCLUSION: Hepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.

PMID:38646529 | PMC:PMC11026605 | DOI:10.3389/fimmu.2024.1387465

Explor Res Clin Soc Pharm. 2024 Apr 8;14:100435. doi: 10.1016/j.rcsop.2024.100435. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: High-alert medication (HAM) is more predictable to cause significant harm to the patient, even when used as intended. The damage related to the HAM lead not only suffering to the patient, but also raise the additional costs associated with care.

OBJECTIVE: Evaluate the incidence of drug-related adverse events related to the use of high-alert medications.

METHODS: It was conducted an active search for information through COCHRANE databases, LILACS, SciELO, SCOPUS, PubMed/MEDLINE and WEB OF SCIENCE. The search strategy included the following terms: "Patient safety", "Medication errors" and "Hospital" and "High Alert Medications" or "Dangerous Drugs" in different combinations. Then two reviewers independently conducted a preliminary evaluation of relevant titles, abstracts and finally full-text. Studies quality was evaluated according to PRISMA declaration.

RESULTS: The systematic review evaluated seven articles, which showed that only 11 HAM identified in the literature could have serious events. The most frequently cited were warfarin (22.2%) which progressed from deep vein thrombosis to gangrene, suggesting lower initial doses, followed by cyclophosphamide (22.2%) and cyclosporine (22.2%) which presented invasive fungal infection and death. In addition to these, morphine was compared with its active metabolite (M6G), with M6G causing fewer serious clinical events related to nausea and vomiting, reducing the need for concomitant use of antiemetics.

CONCLUSIONS: The most reported drug classes in the articles included that were related to incidence of drug-related adverse events in use of high-alert medications: morphine, M6G-glucuronide, haloperidol, promethazine, ivabradine, digoxin, warfarin, ximelagatran, cyclophosphamide, cyclosporine, and ATG. The formulate protocols for the use of these medications, with importance placed on evaluating, among the classes, the medication that causes the least harm.

PMID:38646469 | PMC:PMC11031819 | DOI:10.1016/j.rcsop.2024.100435

Cureus. 2024 Mar 20;16(3):e56559. doi: 10.7759/cureus.56559. eCollection 2024 Mar.

ABSTRACT

Bevacizumab, an anti-vascular epidermal growth factor inhibitor, is approved for the treatment of various cancers. Hypertension, gastrointestinal perforation, bleeding manifestations, impaired wound healing, and cerebrovascular accidents are common side effects associated with the monoclonal antibody. Uncommon cutaneous reactions like exfoliative dermatitis associated with bevacizumab have been documented in the medical literature. We present an unusual case of bevacizumab-induced cutaneous lupus in a patient with metastatic colon cancer that started resolving after discontinuing chemotherapy. Timely intervention was key in preventing the progression of this chemotherapy-induced cutaneous lupus.

PMID:38646279 | PMC:PMC11028020 | DOI:10.7759/cureus.56559

Drug Des Devel Ther. 2024 Apr 17;18:1231-1245. doi: 10.2147/DDDT.S442808. eCollection 2024.

ABSTRACT

BACKGROUND AND AIM: Ultrasound popliteal sciatic nerve block (UPSNB) is commonly performed in foot and ankle surgery. This study aims to assess the use of dexmedetomidine and dexamethasone as adjuvants in UPSNB for hallux valgus (HV) surgery, comparing their efficacy in producing motor and sensory block and controlling postoperative pain. The adverse event rate was also evaluated.

METHODS: This mono-centric retrospective study included 62 adult patients undergoing HV surgery: 30 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg and dexamethasone 4 mg (Group 1), whereas 32 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg, and dexmedetomidine 1 mcg/Kg (Group 2). At first, the visual analogue scale (VAS) was evaluated after 48 hours. The other outcomes were time to motor block regression, evaluation of the first analgesic drug intake, analgesic effect, adverse effects (hemodynamic disorders, postoperative nausea and vomiting (PONV)) and patient satisfaction. The continuous data were analyzed with student's t-test and the continuous one with χ2. Statistical significance was set at a p-value lower than 0.05.

RESULTS: No significant difference was found in VAS after 48 hours (4.5 ± 1.6 vs 4.7 ± 1.7, p = 0.621) to motor block regression (18.9 ± 6.0 vs 18.7 ± 6, p = 0.922). The number of patients that took their first analgesic drug in the first 48 h (p = 0.947 at 6 hours; p = 0.421 at 12 hours; p = 0.122 at 24 hours and p = 0.333 at 48 hours) were not significant. A low and similar incidence of intraoperative hemodynamic disorders was recorded in both groups (hypotension p = 0.593; bradycardia p = 0.881). Neither PONV nor other complication was found. Patients in Group 1 reported a lower degree of interference with sleep (p = 0.001), less interference with daily activities (P = 0.002) and with the affective sphere (P = 0.015) along with a more satisfactory postoperative pain management (p < 0.001) as compared to Group 2.

CONCLUSION: No significant differences were observed in the duration of motor and sensory blockade between patients in both groups. Additionally, both groups showed good pain control with a low rate of adverse effects, even if there was no clinical difference between the groups. However, patients who received dexamethasone reported experiencing less interference with their sleep, daily activities and overall emotional well-being, and overall pain control.

PMID:38645991 | PMC:PMC11032716 | DOI:10.2147/DDDT.S442808

Sci Rep. 2024 Apr 20;14(1):9074. doi: 10.1038/s41598-024-59710-3.

ABSTRACT

Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.

PMID:38643204 | PMC:PMC11032331 | DOI:10.1038/s41598-024-59710-3

Diabetes Ther. 2024 Apr 20. doi: 10.1007/s13300-024-01577-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Second-generation basal insulins like glargine 300 U/mL (Gla-300) have a longer duration of action and less daily fluctuation and interday variability than first-generation ones, such as glargine 100 U/mL (Gla-100). The EF-BI study, a nationwide observational, retrospective study, was designed to compare persistence, acute care complications, and healthcare costs associated with the initiation of such basal insulins (BI) in a real-life setting in France.

METHODS: This study was conducted using the French healthcare claims database (SNDS). Adult patients living with type 1 or type 2 diabetes mellitus (T1DM or T2DM) initiating Gla-300 or Gla-100 ± other hypoglycemic medications between January 1, 2016 and December 31, 2020, and without any insulin therapy over the previous 6 months were included. Persistence was defined as remaining on the same insulin therapy until discontinuation defined by a 6 month period without insulin reimbursement. Hospitalized acute complications were identified using ICD-10 codes. Total collective costs were established for patients treated continuously with each basal insulin over 1-3 years. All comparisons were adjusted using a propensity score based on initial patient/treatment characteristics.

RESULTS: A total of 235,894 patients with T2DM and 6672 patients with T1DM were included. Patients treated with Gla-300 were 83% (T1DM) and 44% (T2DM) less likely to discontinue their treatment than those treated with Gla-100 after 24 months (p < 0.0001). The annual incidence of acute hospitalized events in patients with T2DM treated with Gla-300 was 12% lower than with Gla-100 (p < 0.0001) but similar in patients with T1DM. Comparison of overall costs showed moderate but statistically significant differences in favor of Gla-300 versus Gla-100 for all patients over the first year, and in T2DM only over a 3-year follow-up.

CONCLUSION: Use of Gla-300 resulted in a better persistence, less acute hospitalized events at least in T2DM, and reduced healthcare expenditure. These real-life results confirmed the potential interest of using Gla-300 rather than Gla-100.

PMID:38642261 | DOI:10.1007/s13300-024-01577-8

Medicine (Baltimore). 2024 Apr 19;103(16):e37785. doi: 10.1097/MD.0000000000037785.

ABSTRACT

The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNA < 50 copies/mL; missing-equals-excluded [M = E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints. In total, 201 participants were enrolled in the BICSTaR Canada cohort. The analysis population included 170 participants (TN, n = 10; TE, n = 160), with data collected between November 2018 and September 2020. Of the participants, 88% were male, 72% were White, and 90% had ≥ 1 comorbid condition(s). Median (quartile [Q]1-Q3) age was 50 (39-58) years and baseline CD4 count was 391.5 (109.0-581.0) cells/µL in TN participants and 586.0 (400.0-747.0) cells/µL in TE participants. After 12 months of B/F/TAF treatment, HIV-1 RNA was < 50 copies/mL in 100% (9/9) of TN-active participants and 97% (140/145) of TE-active participants (M = E analysis). Median (Q1-Q3) CD4 cell count increased by +195 (125-307) cells/µL in TN participants and by + 30 (-50 to 123) cells/µL in TE participants. Persistence on B/F/TAF was high through month 12 with 10% (1/10) of TN and 7 % (11/160) of TE participants discontinuing B/F/TAF within 12 months of initiation of treatment. No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 7% (12/169) of participants, leading to B/F/TAF discontinuation in 4 of 169 participants. Improvements in treatment satisfaction were observed in TE participants. B/F/TAF demonstrated high levels of effectiveness, persistence, and treatment satisfaction, and was well tolerated through month 12 in people with HIV treated in routine clinical practice in Canada.

PMID:38640301 | PMC:PMC11029942 | DOI:10.1097/MD.0000000000037785

Medicine (Baltimore). 2024 Apr 19;103(16):e37903. doi: 10.1097/MD.0000000000037903.

ABSTRACT

Complementary and alternative medicine-related liver injuries are increasing globally. Alternative medicine, as an inclusive healthcare practice, is widely accepted in developing and underdeveloped countries. In this context, the traditional systems of medicine in India have been at the forefront, catering to the preventive and therapeutic spectrum in the absence of conclusive evidence for benefits and lack of data on safety. Contrary to popular belief, it is evident that apart from adverse events caused by contamination and adulteration of alternative medicines, certain commonly used herbal components have inherent hepatotoxicity. This narrative review updates our current understanding and increasing publications on the liver toxicity potential of commonly used herbs in traditional Indian systems of medicine (Ayush), such as Tinospora cordifolia (Willd.) Hook.f. & Thomson (Giloy/Guduchi), Withania somnifera (L.) Dunal (Ashwagandha), Curcuma longa L. (Turmeric), and Psoralea corylifolia L. (Bakuchi/Babchi). This review also highlights the importance of the upcoming liver toxicity profiles associated with other traditional herbs used as dietary supplements, such as Centella asiatica (L.) Urb., Garcinia cambogia Desr., Cassia angustifolia Vahl (Indian senna), and Morinda citrofolia L. (Noni fruit). Fortunately, most reported liver injuries due to these herbs are self-limiting, but can lead to progressive liver dysfunction, leading to acute liver failure or acute chronic liver failure with a high mortality rate. This review also aims to provide adequate knowledge regarding herbalism in traditional practices, pertinent for medical doctors to diagnose, treat, and prevent avoidable liver disease burdens within communities, and improve public health and education.

PMID:38640296 | PMC:PMC11029936 | DOI:10.1097/MD.0000000000037903

Cureus. 2024 Mar 18;16(3):e56424. doi: 10.7759/cureus.56424. eCollection 2024 Mar.

ABSTRACT

Background In 2018, the World Health Organisation (WHO) released interim guidelines, advising a change of regimens to dolutegravir-based first- and second-line antiretroviral therapy (ART), based on which, in 2021, the National Aids Control Organisation (NACO) updated its guidelines to include the tenofovir + lamivudine + dolutegravir (TLD) regimen as a first line of therapy for all people living with HIV (PLHIV) and second- and third-line regimens to dolutegravir-based regimens. Considering this change of regimen, the adverse drug reaction (ADR) profiling and longitudinal prescription pattern of antiretroviral and concomitant medications in adult patients at the ART centre of a tertiary care hospital were assessed in this study. Methods Ninety-seven PLHIV out of all the patients who attended the ART centre from September 2021 to July 2022 were enrolled and followed up for six months. The ADRs that occurred during this period were collected along with details of prescription patterns and analyzed by descriptive statistics. Causality assessment for ADR was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Results Seventy-eight percent (n=76 out of 97) of patients experienced at least one ADR, and 128 ADRs were seen in 97 patients. The most common ADRs were increased alkaline phosphatase (39.0%, n=128), dyslipidaemia (12.5%, n=128), and nephrotoxicity (10.1%, n=128). The drug most suspected of causing ADRs was dolutegravir (27.5%, n=342). The most common therapeutic regimen was TLD (71.2%, n=97). The most prescribed drug was lamivudine (30.6%, n=1183). The most prescribed concomitant medication was cotrimoxazole (15%, n=312). Conclusions Dolutegravir-based regimens have been implemented for PLHIV in a phased-out manner from previous non-dolutegravir-based ART regimens, which is in line with the recent NACO guidelines. However, it has also led to an increase in dolutegravir-associated ADRs like increased alkaline phosphatase, dyslipidaemia, and nephrotoxicity. Continuous monitoring of prescriptions and ADRs can add to our knowledge regarding their use and ADRs.

PMID:38638708 | PMC:PMC11024481 | DOI:10.7759/cureus.56424

BMC Pharmacol Toxicol. 2024 Apr 18;25(1):28. doi: 10.1186/s40360-024-00754-6.

ABSTRACT

BACKGROUND: Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems.

METHODS: This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence.

RESULTS: In total, 104 patients (mean ± SD age, 54.1 ± 15.8 years; 53.8% male) were included in the study. An expert panel evaluated the items in the criterion based on their intelligibility, service of purpose, differentiation, and cultural suitability during the translation stage. Content validity index (CVI) score was found to be 0.95. The reliability analysis was performed by applying the test-retest method and calculating correlation coefficient on 30 randomly selected patients one month later. Correlation coefficient (p) was found to be 0.8. To evaluate conceptual validity, 104 patients' pharmacotherapy plans were assessed using both the PAIR and PCNE criteria. The prevalence of DRPs according to PAIR criteria (100.0%) and PCNE (73.1%) were statistically significantly different (p < 0.001).

CONCLUSIONS: As a result, PAIR criteria can identify clinically relevant DRPs in patients with CKD and is a new, validated tool to be used in Turkey, but may not be adequate for patients receiving dialysis. Therefore, it needs to be reviewed and updated for dialysis patients.

PMID:38637817 | PMC:PMC11025200 | DOI:10.1186/s40360-024-00754-6