15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/11/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/11/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Mitochondrial dysfunctions in HIV infection and antiviral drug treatment.

Expert Opin Drug Metab Toxicol. 2019 Nov 12;:

Authors: Ganta KK, Chaubey B

Abstract
Introduction: With the introduction of highly active anti-retroviral therapy (HAART), the treatment of HIV infection has improved radically, shifting the concept of HIV disease from that of a highly mortal epidemic to that of a chronic illness which needs systematic management. However, HAART does not eliminate the virus completely or target the proviral DNA. Hence prolonged use of antiviral drugs is needed for sustaining life. As a consequence, severe side effects emerged. Several parameters involve in causing these adverse effects. Mitochondrial dysfunctions were pointed as one of the common factor among them. It is, therefore, necessary to critically examine the mitochondrial dysfunction in order to understand the side effects.Areas covered: There are many events involved in causing drug-induced side-effects; in this review, we only highlight mitochondrial dysfunctions as one of the events. We present up-to-date findings on mitochondrial dysfunction caused by HIV infection as well as antiviral drug treatment. Both in vivo and in vitro studies on mitochondrial dysfunction like change in morphology, membrane depolarization, mitophagy, mitochondrial DNA depletion and intrinsic apoptosis have been discussed.Expert opinion: Mitochondrial dysfunction is associated with severe complications that often lead to discontinuation or change in the treatment regimen. Prior knowledge of the side effects of antiviral drugs would help in better management and future research should focus to avoid mitochondrial targeting of antiviral drugs while maintaining their antiviral properties.

PMID: 31715109 [PubMed - as supplied by publisher]

Intra-articular facet joint steroid injection-related adverse events encountered during 11,980 procedures.

Eur Radiol. 2019 Nov 11;:

Authors: Kim BR, Lee JW, Lee E, Kang Y, Ahn JM, Kang HS

Abstract
OBJECTIVES: To analyze the incidence and characteristics of intra-articular facet joint injection (FJI)-related adverse events requiring hospitalization and emergency room visits.
METHODS: From January 2007 to December 2017, a total of 11,980 FJI procedures in 6066 patients (mean age 66.8 years, range 15-97 years, M:F = 2004:4062) were performed in our department. Of these, we retrospectively reviewed 489 cases in 432 patients who were hospitalized or visited the emergency room within a month of FJI. FJI-related adverse events were classified as procedure-related complications, drug-related systemic events, or uncertain etiology events, on the basis of consensus of two spine radiologists. This is a descriptive study without statistical analysis.
RESULTS: There were 101 FJI-related adverse event cases in 99 patients (mean age 71.8 years, range 39-97 years, M:F = 39:60). The overall incidence of FJI-related adverse events was 0.84% (101/11,980) per case and 1.63% (99/6066) per patient. The incidence of procedure-related complications and drug-related systemic adverse events was 0.07% (8/11,980) and 0.15% (18/11,980), respectively; the rate of uncertain etiology events was 0.63% (75/11,980). All eight procedure-related complication cases involved major complications. There are seven cases of infectious spondylitis and one was progression of systemic aspergillosis to the spine. One patient died of an uncontrolled infection with infective endocarditis, and two patients experienced partial recovery with neurological sequelae.
CONCLUSIONS: The overall incidence of FJI-related adverse events is low, and procedure-related major complications are rare without dural puncture or epidural hematoma. Nevertheless, infection can occur, resulting in serious outcomes.
KEY POINTS: • The incidence of FJI-related adverse events requiring hospitalization or ER visit was 0.84%. • The incidence of major procedure-related complications was 0.07%. • All major complications were associated with infection and there were no cases of epidural hematoma.

PMID: 31712959 [PubMed - as supplied by publisher]

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies.

Transl Psychiatry. 2019 Nov 11;9(1):282

Authors: Han Y, Yan W, Zheng Y, Khan MZ, Yuan K, Lu L

Abstract
Fentanyl is a powerful opioid anesthetic and analgesic, the use of which has caused an increasing public health threat in the United States and elsewhere. Fentanyl was initially approved and used for the treatment of moderate to severe pain, especially cancer pain. However, recent years have seen a growing concern that fentanyl and its analogs are widely synthesized in laboratories and adulterated with illicit supplies of heroin, cocaine, methamphetamine, and counterfeit pills, contributing to the exponential growth in the number of drug-related overdose deaths. This review summarizes the recent epidemic and evolution of illicit fentanyl use, its pharmacological mechanisms and side effects, and the potential clinical management and prevention of fentanyl-related overdoses. Because social, economic, and health problems that are related to the use of fentanyl and its analogs are growing, there is an urgent need to implement large-scale safe and effective harm reduction strategies to prevent fentanyl-related overdoses.

PMID: 31712552 [PubMed - in process]

Phase 1 trial of olaparib and oral cyclophosphamide in BRCA breast cancer, recurrent BRCA ovarian cancer, non-BRCA triple-negative breast cancer, and non-BRCA ovarian cancer.

Br J Cancer. 2019 02;120(3):279-285

Authors: Lee CK, Scott C, Lindeman GJ, Hamilton A, Lieschke E, Gibbs E, Asher R, Badger H, Paterson R, Macnab L, Kwan EM, Francis PA, Boyle F, Friedlander M

Abstract
BACKGROUND: We conducted a Phase 1 study to evaluate safety and activity of olaparib tablets and oral cyclophosphamide.
METHODS: Patients had metastatic breast cancer (BC) or recurrent high-grade serous ovarian cancer (HGSOC), performance status 0-2, and ≤3 lines of prior therapy. Patients were treated using a dose escalation strategy with cohort expansion once maximal tolerated dose (MTD) was determined. Dose level 1 (DL1): olaparib 300 mg bid, cyclophosphamide 50 mg on days 1, 3, and 5, weekly. DL2: olaparib 300 mg bid, cyclophosphamide 50 mg, days 1-5 weekly.
RESULTS: Of 32 patients, 23 had HGSOC (germline BRCA mutation [gBRCAm] 70%) and 9 had BC (gBRCAm 67%). Four were treated at DL1 and 28 at DL2, the MTD. Haematological adverse events (AEs) were most common: grade 3/4 AEs: lymphopenia 75%, anaemia 31%, neutropenia 37%, thrombocytopenia 47%. Two permanently discontinued treatment due to haematological AEs. In BC, no objective response was reported. Unconfirmed objective response was 48% and 64% for all HGSOC and gBRCAm subset, respectively. CA125 responses were 70% (all HGSOC) and 92% (gBRCAm).
CONCLUSIONS: In HGSOC and BC, olaparib 300 mg bid and cyclophosphamide 50 mg on days 1-5 weekly were tolerable and active, particularly in gBRCAm, and is worthy of further investigation.

PMID: 30655615 [PubMed - indexed for MEDLINE]

Real-world use of sunitinib in Japanese patients with pancreatic neuroendocrine tumors: results from a post-marketing surveillance study.

Cancer Chemother Pharmacol. 2019 01;83(1):201-207

Authors: Sato K, Toyoshima Y, Moriyama S, Endo Y, Ito T, Ohki E

Abstract
BACKGROUND: Sunitinib is approved for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable, locally advanced or metastatic disease. Safety and efficacy data in Japanese patients are limited. We report outcomes from a post-marketing surveillance study of sunitinib treatment in Japanese patients.
METHODS: Sunitinib 37.5 mg once daily was orally administered in Japanese patients aged ≥ 15 years with pNETs. The primary endpoints included adverse events (AEs) occurring during the observation period of 168 days and objective response rate (ORR).
RESULTS: Sunitinib was administered in 62 patients with pNETs. The median duration of treatment was 165 days. At 168 days from the start of treatment, 31 patients were still receiving sunitinib treatment and treatment continuation rate was 50.0%. Of the 31 patients who discontinued treatment, 18 (58.1%) discontinued because of AEs and 16 (51.6%) patients discontinued due to insufficient clinical effect. Of the 18 patients who discontinued due to AEs, 10 did so within 42 days of treatment initiation. The most common all-grade AEs were platelet count decreased (33.9%), diarrhea (29.0%), neutrophil count decreased (27.4%), hypertension (24.2%), and palmar-plantar erythrodysesthesia syndrome (24.2%). In the 51 patients eligible for the efficacy analysis, ORR was 13.7% (95% confidence interval, 5.7-26.3) and clinical benefit rate was 70.6%.
CONCLUSIONS: There were no new safety concerns in real-world use of sunitinib in Japanese patients with pNETs. The short treatment duration likely led to low tumor response. Appropriate AEs management through dose interruption/reduction is essential for sunitinib treatment success in this patient population.

PMID: 30413868 [PubMed - indexed for MEDLINE]

A data-driven method to detect adverse drug events from prescription data.

J Biomed Inform. 2018 09;85:10-20

Authors: Zhan C, Roughead E, Liu L, Pratt N, Li J

Abstract
Drug safety issues such as Adverse Drug Events (ADEs) can cause serious consequences for the public. The clinical trials that are undertaken to assess medicine efficacy and safety prior to marketing, generally, may provide sufficient samples for discovering common ADEs. However, more samples are needed to detect infrequent and rare events. Additionally, clinical trials may not include all subgroups of patients. For these reasons, post-marketing surveillance of medicines is necessary for identifying drug safety issues. Most regulatory agencies use the Spontaneous Reporting Systems to identify associations between medicines and suspected ADEs. Data mining with effective analytical frameworks and large-scale medical data is potentially an alternative method to discover and monitor ADEs. In the present paper, we aim to detect potential ADEs from prescription data by discovering ADE associated prescription sequences. In an ADE associated prescription sequence 〈Dp→Ds〉, the prior medicine Dp leads to an ADE for which the succeeding medicine Ds is dispensed to treat. We propose a data-driven method which integrates (1) a constrained sequential pattern mining to uncover prescription sequences as potential signals of ADEs, (2) domain constraints to eliminate interference signals and (3) an adapted Self-Controlled Case Series model to evaluate the potential signals of ADEs. Despite ample prior works using Electronic Health Records (EHRs), our method utilises pure prescription data which does not contain additional information, e.g. symptoms or diagnoses as included in EHRs. To assess the performance of the proposed method, we apply it to a real-world dataset from the Pharmaceutical Benefits Scheme of Australia. The dataset contains over 50 million records covering approximately 2 million patients. The results demonstrate the effectiveness of our method in identifying both known ADEs and unknown yet suspicious ADEs with limited detection of false positive signals. Comparing to a recognised gold standard, our method successfully detects 67.4% of the positive adverse events while only 8.78% false positives exist.

PMID: 30016721 [PubMed - indexed for MEDLINE]

Strategies for Early Prediction and Timely Recognition of Drug-Induced Liver Injury: The Case of Cyclin-Dependent Kinase 4/6 Inhibitors.

Front Pharmacol. 2019;10:1235

Authors: Raschi E, De Ponti F

Abstract
The idiosyncratic nature of drug-induced liver injury (DILI) represents a current challenge for drug developers, regulators and clinicians. The myriad of agents (including medications, herbals, and dietary supplements) with recognized DILI potential not only strengthens the importance of the post-marketing phase, when urgent withdrawal sometimes occurs for rare unanticipated liver toxicity, but also shows the imperfect predictivity of pre-clinical models and the lack of validated biomarkers beyond traditional, non-specific liver function tests. After briefly reviewing proposed key mechanisms of DILI, we will focus on drug-related risk factors (physiochemical and pharmacokinetic properties) recently proposed as predictors of DILI and use cyclin-dependent kinase 4/6 inhibitors, relatively novel oral anticancer medications approved for breast cancer, as a case study to discuss the feasibility of early detection of DILI signals during drug development: published data from pivotal clinical trials, unpublished post-marketing reports of liver adverse events, and pharmacokinetic properties will be used to provide a comparative evaluation of their liver safety and gain insight into drug-related risk factors likely to explain the observed differences.

PMID: 31708776 [PubMed]

Phase I Trial of Pyragrel, a Novel Thromboxane Synthetase Inhibitor, to Evaluate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers.

Front Pharmacol. 2019;10:1231

Authors: Zou C, Zuo X, Huang J, Hua Y, Yang S, Yang X, Guo C, Tan H, Chen J, Chu Z, Pei Q, Yang G

Abstract
Background and Objective: Inhibition of thrombosis and platelet aggregation through a thromboxane synthetase inhibitor proved to be an effective and promising treatment for cardiovascular and/or cerebrovascular disease (CCVD) patients. This phase I study evaluated the safety, tolerability, and pharmacokinetics of sodium pyragrel, a novel thromboxane A2 synthetase inhibitor, in healthy volunteers. Methods: A total of 84 healthy Chinese volunteers were enrolled in the study and randomized into one of five dosing regimens of intravenous pyragrel, which were single ascending dose (30 to 300 mg), multiple doses (pyragrel 180 mg once daily on Day 1 and Day 6, twice daily from Day 2 to Day 5), 3×3 Latin square crossover (60, 120, 240 mg), and a continuous dose (360 mg in 24 h), respectively. Plasma concentrations were determined using HPLC-MS/MS. Pharmacokinetics parameters were calculated with non-compartment analysis. Results: The maximum plasma concentrations of pyragrel were essentially reached at the end of the 3 h infusion. The pharmacokinetic process of pyragrel and two main metabolites (BBS and BJS) is linear over the 30-300 mg dose range, with no significant accumulation on multiple doses. The urinary excretion of pyragrel accounted for more than 70% of the total drug amount. Preliminary pharmacodynamic results demonstrated that the production of urinary 11-D-HTXB2 was time- and dose-dependently inhibited by single i.v. dose of pyragrel. Conclusions: Pyragrel was well tolerated after single ascending doses up to 300 mg, multiple doses of 180 mg, and continuous administration of 360 mg within 24 h. No drug-related, serious adverse drug reactions occurred during the five-part study. The most common pyragrel-related adverse events (AEs) were total bilirubin (TB)/direct bilirubin (DB) elevations with a relatively low incidence rate and seemed to be dose independent. Given the acceptable safety and appropriate pharmacokinetic properties of sodium pyragrel proven in this study, continued clinical development is warranted. The study was registered at http://www.chictr.org.cn (ChiCTR-IID-16010159).

PMID: 31708774 [PubMed]

Challenges to promote the rational use of psychotropic drugs.

Cad Saude Publica. 2019 03 25;35(3):e00242518

Authors: Nascimento DZD, Marques GM

PMID: 30916182 [PubMed - indexed for MEDLINE]

The authors reply.

Cad Saude Publica. 2019 03 25;35(3):e00033319

Authors: Martins ACM, Giordani F, Guaraldo L, Tognoni G, Rozenfeld S

PMID: 30916175 [PubMed - indexed for MEDLINE]

The Influence of Social Modeling, Gender, and Empathy on Treatment Side Effects.

Ann Behav Med. 2018 05 31;52(7):560-570

Authors: Faasse K, Parkes B, Kearney J, Petrie KJ

Abstract
Background: Social modeling has the capacity to shape treatment outcomes, including side effects.
Purpose: This study investigated the influence of social modeling of treatment side effects, gender, and participant empathy, on side effects of a placebo treatment.
Methods: Ninety-six participants (48 females) completed a study purportedly investigating the influence of modafinil (actually placebo) on alertness and fatigue. The participants were randomly seated with a male or female confederate and saw this confederate report experiencing side effects or no side effects. Participant empathy was assessed at baseline. Changes in modeled and general symptoms, and misattribution of symptoms, were assessed during the session and at 24-hr follow-up.
Results: During the experimental session, seeing side effect modeling significantly increased modeled symptoms (p = .023, d = 0.56) but not general or misattributed symptoms. Regardless of modeling condition, female participants seated with a female model reported significantly more general symptoms during the session. However, response to social modeling did not differ significantly by model or participant gender. At follow-up, the effect of social modeling of side effects had generalized to other symptoms, resulting in significantly higher rates of modeled symptoms (p = .023, d = 0.48), general symptoms (p = .013, d = 0.49), and misattributed symptoms (p = .022, d = 0.50). The experience of modeled symptoms in response to social modeling was predicted by participants' levels of baseline empathy.
Conclusions: Social modeling of symptoms can increase the side effects following treatment, and this effect appears to generalize to a broader range of symptoms and symptom misattribution over time. Higher baseline empathy seems to increase response to social modeling.

PMID: 29860362 [PubMed - indexed for MEDLINE]

Eosinophilic Pneumonias.

J Allergy Clin Immunol Pract. 2018 Sep - Oct;6(5):1455-1461

Authors: Allen J, Wert M

Abstract
The eosinophilic pneumonias are a heterogeneous group of diseases characterized by an increase in eosinophils in lung tissue or bronchoalveolar lavage fluid. Many, but not all, of the eosinophilic pneumonias are also associated with a peripheral blood eosinophilia. The etiologies of eosinophilic lung disease are wide ranging and include parasitic infections, medications or other toxins, autoimmune and inflammatory disease, and malignancies. Some eosinophilic pneumonias have no proven cause or inciting event and are classified as idiopathic. An accurate diagnosis can prove difficult and often relies on a combination of a thorough history and physical examination, including travel and medication history, laboratory and radiographic evaluation, and, in some instances, bronchoscopic and histologic evaluation. Early and accurate diagnosis is imperative in certain diseases, such as acute eosinophilic pneumonia, as delayed diagnosis and treatment can lead to fatal lung disease. Corticosteroids are the mainstay of treatment for many of the eosinophilic pneumonias, particularly for both acute and chronic eosinophilic pneumonias, and prognosis is typically excellent provided treatment is initiated in a timely manner.

PMID: 29735405 [PubMed - indexed for MEDLINE]

Summary and simulation of reported adverse events from epinephrine autoinjectors and a review of the literature.

J Allergy Clin Immunol Pract. 2018 Nov - Dec;6(6):2143-2145.e4

Authors: Shaker M, Toy D, Lindholm C, Low J, Reigh E, Greenhawt M

PMID: 29660429 [PubMed - indexed for MEDLINE]

Twenty Years' Experience with Anaphylaxis-Like Reactions to Local Anesthetics: Genuine Allergy is Rare.

J Allergy Clin Immunol Pract. 2018 Nov - Dec;6(6):2051-2058.e1

Authors: Trautmann A, Goebeler M, Stoevesandt J

Abstract
BACKGROUND: Anaphylaxis-like reactions occur within minutes after the application of local anesthetics (LA), most commonly during dental interventions. Impressive symptoms including respiratory distress or loss of consciousness frequently give rise to a suspicion of allergy and may prompt patients and treating physicians to refuse future LA injections.
OBJECTIVE: Nonallergic mechanisms are responsible for the majority of LA-induced immediate-type reactions. In view of the preponderance of nonallergic reactions, the question arises whether genuine LA allergy may be missed during routine testing procedures.
METHODS: We retrospectively evaluated clinical data and test results from patients referred to our allergy clinic within the past 20 years for diagnostic workup of LA-induced immediate-type reactions.
RESULTS: Of 402 evaluated patients, 29 had an episode of acute urticaria within 30 minutes after LA injections, and the remaining 373 had a history of mainly subjective cutaneous, respiratory, cardiovascular, and neurological complaints. Of the patients reporting urticaria with or without angioedema, 14 were diagnosed with a spontaneous episode of urticaria, 13 had allergic or nonallergic reactions to other agents, and 2 had IgE-mediated LA allergy. LA allergy was definitely excluded by 771 subcutaneous provocation tests with skin test negative LA, thereby demonstrating the high predictive value of negative intradermal testing.
CONCLUSIONS: Skin testing and provocative LA challenge are useful to exclude LA allergy, and this testing procedure seems to be appropriate to identify the extremely rare cases with IgE-mediated LA allergy.

PMID: 29655774 [PubMed - indexed for MEDLINE]

Metabolic screening for patients with second-generation antipsychotic medication: A population-based study from 2004 to 2016.

Schizophr Res. 2018 07;197:618-619

Authors: Lee EHM, Hui CLM, Law EYL, Chan PY, Chang WC, Chan SKW, Chen EYH

PMID: 29477247 [PubMed - indexed for MEDLINE]

Impact of Adverse Event Solicitation on the Safety Profile of SQ House Dust Mite Sublingual Immunotherapy Tablet.

J Allergy Clin Immunol Pract. 2018 Nov - Dec;6(6):2081-2086.e1

Authors: Nolte H, Bernstein DI, Sussman GL, Svanholm Fogh B, Lu S, Husøy B, Nelson HS

Abstract
BACKGROUND: It has been recommended that sublingual immunotherapy (SLIT) safety be assessed using solicited adverse event (AE) collection methods.
OBJECTIVES: The objectives of this study were to describe the impact on the safety profile of SQ house dust mite (HDM) SLIT-tablet (12 SQ-HDM dose) when prespecified local application site reactions were solicited versus unsolicited, and discuss ramifications of AE solicitation.
METHODS: Subjects were randomized to daily 12 SQ-HDM or placebo for up to 52 weeks in 4 double-blinded, multicenter trials. In one trial (NCT01700192; N = 1272), subjects documented daily the presence or absence of 15 World Allergy Organization-defined local application site reactions using a structured questionnaire of closed-ended questions (solicited AEs). Subjects in the other trials were not asked about specific AEs (unsolicited AEs), and AE data were pooled (N = 1287). Analysis was limited to adults aged 18 to 65 years.
RESULTS: Whether AEs were solicited or unsolicited, the most common AEs leading to study discontinuation with 12 SQ-HDM were throat irritation and oral pruritus. Approximately 95% of treatment-related AEs were mild to moderate. Placebo-subtracted frequencies of local application site reactions associated with 12 SQ-HDM were higher when solicited versus unsolicited (ie, throat irritation, 46% vs 13%, respectively; oral pruritus, 47% vs 17%; ear pruritus, 40% vs 4%; mouth swelling, 8% vs 2%; tongue ulceration, 10% vs 0%; mouth ulceration, 7% vs <1%).
CONCLUSIONS: Qualitatively, the safety profile of 12 SQ-HDM was similar when AEs were solicited versus unsolicited; hence, solicitation did not alter the safety profile. Higher observed frequencies of local application site reactions with AE solicitation may be partly due to suggestive reporting bias, as observed in placebo-treated subjects.

PMID: 29432959 [PubMed - indexed for MEDLINE]

Integrating adverse outcome pathways (AOPs) and high throughput in vitro assays for better risk evaluations, a study with drug-induced liver injury (DILI).

ALTEX. 2019 Nov 02;:

Authors: Khadka KK, Chen M, Liu Z, Tong W, Wang D

Abstract
The emergence of high throughput in vitro assays has the potential to significantly improve toxicological evaluations and lead to more efficient, accurate, and less animal-intensive testing. However, directly using all available in vitro assays in a model is usually impractical and inefficient. On the other hand, mechanistic knowledge has always been critical for toxicological evaluations and should not be ignored even with the increasing availability of data. In this paper, we illustrate a promising approach to integrating mechanistic knowledge with multiple data sources for in vitro assays, using drug-induced liver injury (DILI) as an example. The adverse outcome pathway (AOP) framework was used as a source for mechanistic knowledge and as a selection tool for high throughput predictors. Our results confirmed the value of AOPs as a knowledge source for understanding adverse events, and showed that the majority of drugs classified as most-DILI-concern were mapped to AOPs related to liver toxicity found in AOPwiki.  AOPs were also used effectively to select a subset of assays from the Tox21 and L1000 projects as the predictors in predictive modeling of DILI risk. Together with previously published drug properties for daily dose, lipophilicity, and reactive metabolite formation, these assay endpoints were used to build a penalized logistic regression model for assessing DILI risk. This model obtained an accuracy of 0.91, thus confirming the potential power of integrating mechanistic knowledge with high throughput assays for toxicological evaluations. The results also provide a roadmap for data integration that could be used for other adverse effects.

PMID: 31707421 [PubMed - as supplied by publisher]

A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies.

Eur J Cancer. 2019 Nov 07;124:15-24

Authors: Guo CW, Alexander M, Dib Y, Lau PKH, Weppler AM, Au-Yeung G, Lee B, Khoo C, Mooney D, Joshi SB, Creati L, Sandhu S

Abstract
Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.

PMID: 31707280 [PubMed - as supplied by publisher]