J Med Virol. 2023 Jul;95(7):e28947. doi: 10.1002/jmv.28947.

ABSTRACT

Azvudine is recommended by Chinese health authorities for COVID-19 treatment but has not been tested in real-world clinical studies. This study aimed to evaluate the real-world effectiveness of Azvudine among COVID-19 nonhospitalized patients. This was a retrospective cohort study, looking at nonhospitalized patients who tested positive for SARS-CoV-2. Patients admitted between December 19, 2022 and January 5, 2023 were included. Those who received Azvudine treatment were in the Azvudine group, while those who received supportive treatment were the control group. The primary outcome was the disease progression rate by Day 28. Secondary outcomes were individual disease progression outcomes (death or COVID-19-related hospitalization) and duration of fever. The safety outcomes were assessed based on adverse events (AEs) overall, as well as AEs that were considered to be related to the drug. A total of 804 patients with high risk for progression were enrolled in our study. Among them, 317 (39.43%) received treatment with Azvudine. Our study found that Azvudine could reduce the rate of disease progression, as well as rate of COVID-19-related hospitalization in patients comparing the control group. Furthermore, if taken within 3 days of the onset of symptoms, it could also shorten the duration of fever. Despite a higher incidence of drug-related AEs compared to supportive treatment, the majority of these were mild. Azvudine has been found to be effective in reducing the rate of disease progression of COVID-19, albeit with a slight increase in AEs.

PMID:37470209 | DOI:10.1002/jmv.28947

DEN Open. 2023 Jul 17;4(1):e271. doi: 10.1002/deo2.271. eCollection 2024 Apr.

ABSTRACT

Dabigatran is a useful and widely used drug for stroke prevention in patients with atrial fibrillation. However, it has been reported to cause esophagitis. Herein, we report the case of a 77-year-old man with dabigatran-induced esophagitis with blue pigmentation, which is known to be a rare adverse effect. The patient presented to our hospital with a tightness of the chest and anorexia. Computed tomography revealed a thickening of the entire esophageal wall, with an upper esophageal predominance. Esophagogastroduodenoscopy was performed, which showed that the cervical and upper thoracic esophagus had blue pigmentation with edematous changes, partial narrowing, and longitudinal sloping. We replaced dabigatran with edoxaban, a similar anticoagulation medication. The patient was closely monitored for 1 month after switching to edoxaban. The follow-up esophagogastroduodenoscopy showed marked improvements, revealing resolution of the bluish discoloration and edematous changes, and the patient's complaints regarding the tightness of the chest and anorexia were also resolved. It is important to recognize that such side effects can occur with dabigatran, a drug that is frequently used in daily practice. Considering the fact that strong edematous changes can cause indigo carmine pigmentation associated with dabigatran stagnation, we recommend switching to another anticoagulant if esophagitis occurs during dabigatran administration.

PMID:37469668 | PMC:PMC10352591 | DOI:10.1002/deo2.271

Belitung Nurs J. 2021 Jun 28;7(3):195-202. doi: 10.33546/bnj.1337. eCollection 2021.

ABSTRACT

BACKGROUND: Patients with newly diagnosed pulmonary tuberculosis often suffer from adverse drug reaction symptoms, which leads to the automatic discontinuation of anti-tuberculosis drugs. Thus, understanding symptom experience of adverse drug reactions is necessary.

OBJECTIVE: This study aimed to examine differences in symptoms experienced in four dimensions: presence, frequency, severity, and distress of adverse drug reactions, between male and female patients.

METHODS: This was a quantitative survey with a cross-sectional design, with data collected between January and April 2020. A total of 394 patients with newly diagnosed pulmonary tuberculosis was selected through a purposive sampling technique. The symptom experiences of adverse drug reactions were measured using a validated instrument. Data were analyzed using mean, standard deviation, and independent t-test.

RESULTS: The most commonly reported symptom was itchiness (24.1% in males and 34.9% in females). Vomiting occurred as the most frequent symptom among males (x̄ ± SD = 2.73 ± .88), and fatigue was found to be the most severe and distressing symptom across male patients (x̄ ± SD = 2.50 ± 1.61 and 2.06 ± 1.30, respectively). In contrast, yellowing of the eyes and skin was most frequent and severe among females (x̄ ± SD = 3.17 ± .75 and 3.83 ± 1.47, respectively). In addition, flu-like symptoms were evaluated as the most distressing symptom for female patients (x̄ ± SD = 2.80 ± 1.09). The symptom burdens of the females ranged significantly and reached higher than those of the male patients at a p-value of .05 (t = 3.33).

CONCLUSION: Females taking anti-tuberculosis drugs should be carefully monitored to deal with adverse drug reaction symptoms. This finding would help to decrease the severity of disease and improve their quality of life.

PMID:37469342 | PMC:PMC10353636 | DOI:10.33546/bnj.1337

Nat Commun. 2023 Jul 19;14(1):4323. doi: 10.1038/s41467-023-40064-9.

ABSTRACT

In vitro secondary pharmacology assays are an important tool for predicting clinical adverse drug reactions (ADRs) of investigational drugs. We created the Secondary Pharmacology Database (SPD) by testing 1958 drugs using 200 assays to validate target-ADR associations. Compared to public and subscription resources, 95% of all and 36% of active (AC50 < 1 µM) results are unique to SPD, with bias towards higher activity in public resources. Annotating drugs with free maximal plasma concentrations, we find 684 physiologically relevant unpublished off-target activities. Furthermore, 64% of putative ADRs linked to target activity in key literature reviews are not statistically significant in SPD. Systematic analysis of all target-ADR pairs identifies several putative associations supported by publications. Finally, candidate mechanisms for known ADRs are proposed based on SPD off-target activities. Here we present a freely-available resource for benchmarking ADR predictions, explaining phenotypic activity and investigating clinical properties of marketed drugs.

PMID:37468498 | PMC:PMC10356841 | DOI:10.1038/s41467-023-40064-9

Drug Ther Bull. 2023 Jul 19:dtb-2023-000040. doi: 10.1136/dtb.2023.000040. Online ahead of print.

NO ABSTRACT

PMID:37468231 | DOI:10.1136/dtb.2023.000040

Commun Med (Lond). 2023 Jul 19;3(1):99. doi: 10.1038/s43856-023-00315-8.

ABSTRACT

BACKGROUND: Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.

METHODS: This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan-Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.

RESULTS: Here we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994-4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.

CONCLUSIONS: DOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients.

PMID:37468544 | DOI:10.1038/s43856-023-00315-8

Asian Pac J Allergy Immunol. 2023 Jul 16. doi: 10.12932/AP-180222-1335. Online ahead of print.

ABSTRACT

BACKGROUND: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce.

OBJECTIVE: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma.

METHODS: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients.

RESULTS: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years.

CONCLUSIONS: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

PMID:37466961 | DOI:10.12932/AP-180222-1335

Am J Hematol. 2023 Jul 19. doi: 10.1002/ajh.27031. Online ahead of print.

ABSTRACT

Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.

PMID:37466271 | DOI:10.1002/ajh.27031

Lancet Reg Health Eur. 2023 Apr 21;30:100639. doi: 10.1016/j.lanepe.2023.100639. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied.

METHODS: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 μg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12.

FINDINGS: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events.

INTERPRETATION: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments.

FUNDING: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

PMID:37465323 | PMC:PMC10350848 | DOI:10.1016/j.lanepe.2023.100639

Front Psychiatry. 2023 Jul 3;14:1203497. doi: 10.3389/fpsyt.2023.1203497. eCollection 2023.

ABSTRACT

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.

PMID:37465252 | PMC:PMC10351415 | DOI:10.3389/fpsyt.2023.1203497

Med Oncol. 2023 Jul 17;40(8):246. doi: 10.1007/s12032-023-02106-6.

ABSTRACT

Cancer treatment is one of the most challenging topics in medical sciences. Different methods such as chemotherapy, tumor surgery, and immune checkpoint inhibitors therapy (ICIs) are potential approaches to treating cancer and killing tumor cells, but clinical studies have shown that they have been successful for a limited group of patients. Using viruses as a treatment can be considered as an effective treatment in the field of medicine. This is considered as a potential treatment, especially in comparison to chemotherapy, which has severe side effects related to the immune system. Most oncolytic viruses (OVs) have the potential to multiply in cancer cells, which are more than normal cells in malignant tissue and can induce immune responses. Therefore, tons of efforts and research have been started on the utilization of OVs as a treatment for cancer and have shown promising in treating cancers with less side effects. In this article, we have gathered studies about oncolytic viruses and their effectiveness in cancer treatment.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Omid Salahi] Last name [Ardekani], Author 2 Given name: [Mohammad Mehdi] Last name [Fazeli], Author 3 Given name: [Nillofar Asadi] Last name [Jemezghani]. Also, kindly confirm the details in the metadata are correct.Confirmed.

PMID:37458862 | DOI:10.1007/s12032-023-02106-6

Eur Rev Med Pharmacol Sci. 2023 Jul;27(13):6384-6392. doi: 10.26355/eurrev_202307_32998.

ABSTRACT

OBJECTIVE: Obesity is one of the main concerns for public health and is becoming an increasingly widespread problem worldwide. Women are more likely to require a cesarean section and have a longer hospital stay after delivery. Excess body weight can interfere with ovulation and make it more difficult for embryos to implant in the uterus. A high body mass index (BMI) has controversial effects on the outcomes of medically assisted reproduction treatments (IVF) and, if careful counseling is not performed, medical-legal risks may be incurred. While some researchers argue that obesity does not particularly affect ART outcomes, other studies claim that a high BMI does not interfere with embryonic development. Both the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) has stated that there is no clear evidence supporting a BMI limit for IVF treatment and that each patient should be evaluated on an individual basis. The purpose of our study was to evaluate whether performing in vitro fertilization on these patients increases the risk of medical, surgical, and anesthetic complications of oocyte retrieval.

PATIENTS AND METHODS: From January 2011 to December 2022, all patients with BMI higher than 25 were enrolled in the study (n=766). Complications and risks related to oocyte retrieval were evaluated, and patients were divided according to BMI groups.

RESULTS: With the one-way ANOVA test, all groups were compared with the control group, and none showed statistically significant differences, only the number of produced embryos in the BMI group between 30-34.9 was lower and statistically significant.

CONCLUSIONS: Only one study has analyzed these aspects, mainly focusing on the need for anesthesia drugs and any related complications, and the same author reported greater difficulty in performing oocyte retrieval. The same study recorded an increase in incomplete oocyte retrievals. Our work does not confirm any of these impressions.

PMID:37458655 | DOI:10.26355/eurrev_202307_32998

J Pharm Pharm Sci. 2023 Jun 30;26:11453. doi: 10.3389/jpps.2023.11453. eCollection 2023.

ABSTRACT

Purpose: Coronavirus disease 2019 (COVID-19) mRNA vaccines are used worldwide to prevent severe symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IgA nephropathy (IgAN) is the most common form of glomerular injury after COVID-19 vaccination; however, because of the low frequency of such events, only a few reports have been published. A large pharmacovigilance database of real-world spontaneous adverse event (AE) reports is essential for evaluating the drug-associated safety signals regarding rare AEs. Herein, we aimed to investigate the frequency of IgAN after the COVID-19 vaccination, using the Japanese Adverse Drug Event Report (JADER) database. Methods: Data on drug-associated AEs reported between April 2004 and May 2022 were obtained from the JADER database on the Pharmaceuticals and Medical Devices Agency website. To evaluate the safety signals for the targeted AEs, reporting odds ratios (RORs), information components (ICs), and their 95% confidence intervals (CIs) were calculated using two-by-two contingency tables. Results: A total of 697,885 cases were included in the analysis. Safety signals were detected for IgAN (ROR: 6.49, 95% CI: 4.38-9.61; IC: 2.27, 95% CI: 1.70-2.83). Of 30 cases for IgAN associated with COVID-19 mRNA vaccines, 16 had information available on time to onset. Of the 16 cases, 11 occurred ≤2 days after vaccination, and two occurred >28 days after vaccination. Conclusion: These results suggest that, compared with other drugs, COVID-19 vaccination is associated with a higher frequency of IgAN. Monitoring of gross hematuria following COVID-19 vaccination should be needed.

PMID:37456806 | PMC:PMC10348063 | DOI:10.3389/jpps.2023.11453

Iran J Med Sci. 2023 Jul;48(4):430-432. doi: 10.30476/ijms.2022.96239.2776.

NO ABSTRACT

PMID:37456210 | PMC:PMC10349163 | DOI:10.30476/ijms.2022.96239.2776

J Am Nutr Assoc. 2023 Jul 17:1-10. doi: 10.1080/27697061.2023.2233008. Online ahead of print.

ABSTRACT

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success.

OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks.

RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function.

CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

PMID:37459747 | DOI:10.1080/27697061.2023.2233008

Epilepsy Behav. 2023 Jul 15;145:109348. doi: 10.1016/j.yebeh.2023.109348. Online ahead of print.

ABSTRACT

INTRODUCTION: Infantile epileptic spasms syndrome (IESS) is characterized by epileptic spasms, regardless of hypsarrhythmia on electroencephalogram or neurodevelopmental delay. In Japan, pyridoxal 5'-phosphate (PLP) is often used as the first-line treatment for IESS because it is effective in a certain number of patients. Although several studies have reported serious adverse events following PLP treatment, no study has investigated the risk factors for such occurrences.

OBJECTIVE: To investigate adverse events associated with PLP therapy for the treatment of IESS and to identify the associated risk factors.

MATERIALS AND METHODS: We retrospectively evaluated adverse events in 59 patients with IESS at Tottori University Hospital between January 1995 and September 2022. We subsequently collected and analyzed their clinical data and analyzed the risk factors associated with each adverse event. The cutoff values and relative risk (RR) were analyzed for items with significant associations with adverse events.

RESULTS: Twenty-seven (51.9%) participants experienced adverse events, including vomiting in 16 participants (59.3%), elevated liver enzyme levels in 15 participants (55.6%), and rhabdomyolysis in two participants (3.4%). No significant differences were observed between the non-adverse events group and the overall adverse events group, as well as between the non-adverse events group and the vomiting group, in terms of the factors examined. However, when comparing the non-adverse events group with the group with elevated liver enzyme levels, age at PLP treatment showed a negative correlation, whereas PLP dose showed a positive correlation with elevated liver enzyme levels. The cutoff dose was 40 mg/kg/day (73.3% sensitivity and 60.7% specificity), and the cutoff age was 9 months (100% sensitivity and 40.0% specificity). RRs of doses ≥40 mg/kg/day and age <9 months were 2.6 and 3.6, respectively.

CONCLUSIONS: Adverse events of PLP therapy, including vomiting, elevated liver enzymes, and rhabdomyolysis, were observed in approximately half of the participants. Age under 9 months and a dose ≥40 mg/kg/day were identified as risk factors for elevation of liver enzymes on PLP treatment in infants with IESS, with rhabdomyolysis can occur in the younger or higher dose cases.

PMID:37459718 | DOI:10.1016/j.yebeh.2023.109348

Rev Prat. 2023 Jun;73(6):641-650.

ABSTRACT

TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.

PMID:37458554

Cureus. 2023 Jul 14;15(7):e41889. doi: 10.7759/cureus.41889. eCollection 2023 Jul.

ABSTRACT

Pembrolizumab is a monoclonal antibody frequently used as immunotherapy for lung cell carcinoma that has been reported to cause hypothyroidism and myasthenia gravis among other, unwanted side effects. Here, we present an interesting case of a 77-year-old male previously diagnosed with lung adenocarcinoma managed with pembrolizumab. Initially, he was admitted after a mechanical fall sustaining a facial laceration and subacute fracture in the nasal bone. However, during the workup, thyroid-stimulating hormone (TSH) was found to be elevated, which was attributed to the history of pembrolizumab usage.

PMID:37457610 | PMC:PMC10348603 | DOI:10.7759/cureus.41889

Res Pract Thromb Haemost. 2023 Jun 14;7(5):100279. doi: 10.1016/j.rpth.2023.100279. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: With the development of thrombopoietin receptor agonists, the prognosis of immune thrombocytopenia (ITP) in patients in whom there was a poor response to first-line treatment has greatly improved. However, there are still some patients who are refractory to eltrombopag.

OBJECTIVES: To explore the efficacy and safety of eltrombopag combined with low-dose cyclosporine in the management of patients with refractory ITP.

METHODS: A total of 21 participants with ITP who failed to respond to multiple lines of therapy (including a daily dose of 75 mg of eltrombopag for at least 30 days) treated at The First Affiliated Hospital of Zhejiang Chinese Medical University between January 2018 and August 2022 were included. All enrolled patients subsequently received 50 mg of eltrombopag daily and low-dose cyclosporine (3 mg/kg/d, with an initial target concentration of 75-120 ng/mL). The efficacy and safety of the combined therapies were evaluated.

RESULTS: A total of 76.2% (16/21) of the patients responded to the combination of cyclosporine and eltrombopag, with a median time to response of 14.5 (range, 5-37) days. A complete response (platelet count ≥ 100 × 109/L) was observed in 81.3% (13/16) of the patients, among whom 1 patient experienced relapse due to self-reduction in eltrombopag. During a median follow-up of 180 days, there were no relapses, and 70% (7/10) of the patients successfully stopped or decreased concomitant ITP medications. One patient had both a catheter-related deep vein thrombosis and a venous cerebral thrombotic event later; no other severe drug-related adverse events were observed.

CONCLUSION: Combining low-dose cyclosporine with eltrombopag may be an effective alternative for multirefractory ITP that is nonresponsive to eltrombopag alone.

PMID:37456916 | PMC:PMC10339056 | DOI:10.1016/j.rpth.2023.100279

JHEP Rep. 2023 Apr 29;5(8):100782. doi: 10.1016/j.jhepr.2023.100782. eCollection 2023 Aug.

ABSTRACT

BACKGROUND & AIMS: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis.

METHODS: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22-24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0-4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs).

RESULTS: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22-24 of PEDFIC 2 in sBAs was -201 μmol/L (p <0.0001). For cohort 1B and cohort 2, mean changes from odevixibat initiation to weeks 22-24 in sBAs were -144 and -104 μmol/L, respectively. The proportion of positive pruritus assessments in the first 24-week period of PEDFIC 2 was 33%, 56%, and 62% in cohorts 1A, 1B, and 2, respectively. Most TEAEs were mild or moderate. No drug-related serious TEAEs occurred.

CONCLUSIONS: Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus.

CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03659916).

IMPACT AND IMPLICATIONS: Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.

PMID:37456676 | PMC:PMC10338319 | DOI:10.1016/j.jhepr.2023.100782