|
|
|
| Analysis on immune checkpoint inhibitor therapy-associated autoimmune encephalitis based on the US Food and Drug Adverse Event Reporting System |
| WU Tingxi1 XU Chang2 ZHANG Yang3 SHI Yanfeng4 GUO Heng3 XU Bei1 ZHAO Zhigang1 |
1.Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;
2.Clinical Trials Institutions for Drugs and Medical Devices, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
3.Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
4.Center of Excellence for Omics Research, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
|
|
|
|
Abstract Objective To evaluate the risk of immune-associated encephalitis (AIE) caused by immune checkpoint inhibitors (ICI) based on the US Food and Drug Adverse Reaction Reporting System. Methods Adverse event reports of ICI (including Navulizumab, Parbolizumab, Attilizumab, Abvizumab, Duvarizumab, Cemiplimab, Ipimimumab, and Tremelimumab) were collected from FAERS database from 1Q2011 to 4Q2021. The risk, occurrence time, patient outcome, and ICI reintroduction of AIE adverse events were evaluated by ROR. Signal was considered to exist when the number of reported adverse events related to the target drug was ≥ 3 and the lower limit of 95% ROR signal was ≥ 1. Results A total of 865 adverse events of AIE were reported, involving 234 patients receiving ICI therapy. The signal emerged in Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab with Ipilimumab, and durvalumab with Tremelimumab, with Durvalumab having the strongest signal (ROR 95% CI: 40.97 [25.70-65.31]). Nivolumab plus ipilimumab had a higher risk of AIE compared to Nivolumab monotherapy (ROR 95% CI: 33.16 [25.49-43.15]), with a shorter period of onset of time(median 60 days). More than 70% of patients with ICI-associated AIE required hospitalization or prolonged hospital stay, with a fatality rate of 18.80% (44 cases). No reports of ICI resumption were collected. Conclusion The risk of AIE induced by ICI is different, and ICI-associated AIE tended to occur within three months after ICI treatment, which should attract clinical attention.
|
|
|
|
|
|
[1] Duong SL，Barbiero FJ，Nowak RJ，et al. Neurotoxicities associated with immune checkpoint inhibitor therapy [J]. J Neurooncol，2021，152（2）：265-277.
[2] Cuzzubbo S，Javeri F，Tissier M，et al. Neurological adverse events associated with immune checkpoint inhibitors： Review of the literature [J]. Eur J Cancer，2017，73：1-8.
[3] Nersesjan V，McWilliam O，Krarup LH，et al. Autoimmune Encephalitis Related to Cancer Treatment With Immune Checkpoint Inhibitors：A Systematic Review [J]. Neurology，2021，97（2）：e191-e202.
[4] Fan Q，Hu Y，Yang C，et al. Myocarditis following the use of different immune checkpoint inhibitor regimens： A real-world analysis of post-marketing surveillance data [J]. Int Immunopharmacol，2019，76：105866.
[5] Williams TJ，Benavides DR，Patrice KA，et al. Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer [J]. JAMA Neurol，2016，73（8）：928-933.
[6] Simonaggio A，Michot JM，Voisin AL，et al. Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer [J]. JAMA Oncol，2019，5（9）：1310-1317.
[7] Moore N，Thiessard F，Begaud B. The history of disproportionality measures （reporting odds ratio，proportional reporting rates） in spontaneous reporting of adverse drug reactions [J]. Pharmacoepidemiol Drug Saf，2005，14（4）：285-286.
[8] Wu T，Zhang Y，Shi Y，et al. Safety of Glucagon-Like Peptide-1 Receptor Agonists： A Real-World Study Based on the US FDA Adverse Event Reporting System Database [J]. Clin Drug Investig，2022，42（11）：965-975.
[9] 周健，陈力.索拉非尼的不良反应信号挖掘[J].中国医药导报，2018，15（14）：111-115.
[10] Chen G，Zhang C，Lan J，et al. Atezolizumab-associated encephalitis in metastatic breast cancer：A case report[J].Oncol Lett，2022，24（3）：324.
[11] Puzanov I，Diab A，Abdallah K，et al. Managing toxicities associated with immune checkpoint inhibitors： consensus recommendations from the Society for Immunotherapy of Cancer （SITC） Toxicity Management Working Group [J]. J Immunother Cancer，2017，5（1）：95.
[12] Harrison RA，Tummala S，de Groot J. Neurologic Toxicities of Cancer Immunotherapies：a Review [J]. Curr Neurol Neurosci Rep，2020，20（7）：27.
[13] Martínez-Vila C，Laguna JC，Segui E，et al. Encephalitis Associated With Immune Checkpoint Inhibitor Treatment in Patients With Melanoma [J]. J Immunother，2021，44（5）：204-207.
[14] Shechtman Y，Shalata W，Khoury R，et al. Encephalitis Induced by Durvalumab During Treatment of Metastatic Small-Cell Lung Cancer：Illustrative Case and Review of the Literature [J]. J Immunother，2021，44（7）：243-247.
[15] Graus F，Titulaer MJ，Balu R，et al. A clinical approach to diagnosis of autoimmune encephalitis [J]. Lancet Neurol，2016，15（4）：391-404.
[16] Nalbanto■lu M，Altunrende B，Tun?觭er ■G，et al. Autoimmune Encephalitis After Treatment of Hodgkin’s Lymphoma with the Immune Checkpoint Inhibitor Nivolumab [J]. Noro Psikiyatr Ars，2021，58（2）：163-165.
[17] Gkoufa A，Gogas H，Diamantopoulos PT，et al. Encephalitis in a Patient With Melanoma Treated With Immune Checkpoint Inhibitors：Case Presentation and Review of the Literature [J]. J Immunother，2020，43（7）：224-229.
[18] Couey MA，Bell RB，Patel AA，et al. Delayed immune-related events （DIRE） after discontinuation of immunotherapy： diagnostic hazard of autoimmunity at a distance [J]. J Immunother Cancer，2019，7（1）：165.
[19] Kazandjian D，Suzman DL，Blumenthal G，et al. FDA Approval Summary： Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy [J]. Oncologist，2016，21（5）：634-642.
[20] Pan PC，Haggiagi A. Neurologic Immune-Related Adverse Events Associated with Immune Checkpoint Inhibition [J]. Curr Oncol Rep，2019，21（12）：108.
[21] Larkin J，Chmielowski B，Lao CD，et al. Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma，Including a Case Series of Encephalitis [J]. Oncologist，2017，22（6）：709-718.
[22] Reynolds KL，Guidon AC. Diagnosis and Management of Immune Checkpoint Inhibitor-Associated Neurologic Toxicity：Illustrative Case and Review of the Literature [J]. Oncologist，2019，24（4）：435-443.
[23] Albandar HJ，Fuqua J，Albandar JM，et al. Immune-Related Adverse Events （irAE） in Cancer Immune Checkpoint Inhibitors （ICI） and Survival Outcomes Correlation： To Rechallenge or Not? [J]. Cancers （Basel），2021，7，13（5）：989.
[24] Fellner A，Makranz C，Lotem M，et al. Neurologic complications of immune checkpoint inhibitors [J]. J Neurooncol，2018，137（3）：601-609.
[25] Haanen J，Carbonnel F，Robert C，et al. Management of toxicities from immunotherapy： ESMO Clinical Practice Guidelines for diagnosis，treatment and follow-up [J]. Ann Oncol，2017，28（suppl_4）：iv119-iv142. |
|
|
|
