Immune Checkpoint Inhibitor–Associated Myositis

Anquetil, Céline; Salem, Joe‐Elie; Lebrun‐Vignes, Bénédicte; Johnson, Douglas B.; Mammen, Andrew L.; Stenzel, Werner; Léonard-Louis, Sarah; Benveniste, Olivier; Moslehi, Javid; Allenbach, Yves

doi:10.1161/circulationaha.118.035898

Cited by 159 publications

(87 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many cases of myasthenia gravis also reported cardiac arrhythmias or myocardial infarction even in cases where myocarditis was not reported, suggesting that myocarditis may be more common than recognized, and highlighting the need for diagnostic assessment for myocarditis and myositis (assessing creatinine kinase and troponin I) in patients with myasthenia gravis. Notably, the myasthenia gravis associated with ICI may be distinct from the de novo syndrome, as acetylcholinesterase receptor antibodies are frequently negative, and there is a high incidence of concurrent myositis [13].…”

Section: Discussionmentioning

confidence: 99%

“…While pharmacovigilance data may lack detailed clinical information, using this approach may help rigorously identify drug-toxicity associations. Herein, we leverage a large pharmacovigilance database (Vigibase), which has been used to characterize other ICI-induced toxicities [5,[12][13][14][15][16], to further define the neurologic toxicities associated with ICI.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Johnson¹,

Manouchehri²,

Haugh³

et al. 2019

j. immunotherapy cancer

Self Cite

280

257

View full text Add to dashboard Cite

Background: Immune checkpoint inhibitors (ICI) produce durable antitumor responses but provoke autoimmune toxicities, including uncommon but potentially devastating neurologic toxicities. The clinical features, including the spectrum, timing, and outcomes, of ICI-induced neurologic toxicities are not well characterized. Methods: We performed disproportionality analysis using Vigibase, the World Health Organization pharmacovigilance database, comparing neurologic adverse event (AE) reporting in patients receiving ICIs vs. the full database. Neurologic AEs were classified by group queries using Medical Dictionary for Regulatory Activities, between database inception to September 28, 2018. Associations between ICIs and neurologic AEs were assessed using reporting odds ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and AEs using disproportionate Bayesian reporting; IC 025 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. Results: Among the full database, 18,518,994 AEs were reported, including 48,653 with ICIs. ICIs were associated with higher incidence of myasthenia gravis (0.47% of ICI reports vs. 0.04% of the full database, ROR 16.5 [95% CI 14. 5-18.9]; IC 025 3.31), encephalitis (0.51% vs. 0.05%, ROR 10.4 [95% CI 9.2-11.8]; IC 025 3.15), peripheral neuropathy (1. 16% vs. 0.67%, IC 025 0.68), and meningitis (0.15% vs. 0.06%, ROR 3.1 [95% CI 2.5-3.9]; IC 025 1.01). Myasthenia gravis and encephalitis were associated with anti-PD-1 whereas other neurologic AEs were associated with anti-CTLA-4. Myasthenia gravis was characterized by high fatality rates (~20%), early onset (median 29 days), and frequent concurrent myocarditis and myositis; whereas other neurologic AEs had lower fatality rates (6-12%), later onset (median 61-80 days), and were non-overlapping. Conclusions: ICIs produce a spectrum of distinct classes of neurologic AEs that can cause significant morbidity and mortality and tend to occur early and with class-specific associations.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Johnson¹,

Manouchehri²,

Haugh³

et al. 2019

j. immunotherapy cancer

Self Cite

280

257

View full text Add to dashboard Cite

show abstract

“…8,9 Rarely, irAEs can target the muscle, heart, or central nervous system, and these systems are generally associated with a higher rate of steroid-refractoriness and mortality. 10,11 A more comprehensive consideration of irAE prevalence, diagnosis, and treatment is provided in the recent update to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Management of Immunotherapy-Related Toxicities 12 and the review by Michot et al 13 Common Themes in PD-1, PD-L1, and CTLA-4 Between Autoimmunity and irAEs There are currently no clinically useful biomarkers that preemptively identify patients who will experience severe irAEs. This lack of predictability adds to the uncertainty of considering ICI therapy for patients with known or presumed autoimmune disease.…”

Section: Pathophysiology Of Iraes and Autoimmune Disordersmentioning

confidence: 99%

Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors

Kennedy

Bhatia

Thompson

et al. 2019

Journal of the National Comprehensive Cancer Network

100

View full text Add to dashboard Cite

The use of immune checkpoint inhibitors (ICIs) is rapidly expanding to the treatment of many cancer types, both in the metastatic setting and as an adjuvant to other therapies. Clinical trials using ICIs have largely excluded patients with preexisting autoimmune diseases due to concerns for increased toxicity. However, emerging evidence shows that ICIs may be considered in some patients with autoimmunity. This review discusses the commonalities between clinical autoimmune diseases and ICI-induced immunotherapy-related adverse events, and summarizes the existing case series that describes patients with solid tumors who have a preexisting autoimmune disease. This review also discusses which patients with autoimmunity could be considered reasonable candidates for ICI therapy.

show abstract

“…In this context, elevated concentrations of cTnT were demonstrated despite normal heart structure and function possibly because commercial assays detect Tn isoforms expressed by the diseased muscle. 10 Because myositis is an emerging immune-related AE of ICPis, 11 this possibility should not be overlooked. Likewise, mild elevations in cTn may be the result of inflammation of the subepicardial myocardium during pericarditis.…”

Section: What Ctn Measures and What Elevated Levels Meanmentioning

confidence: 99%

Identification and Management of Immune Checkpoint Inhibitor–Related Myocarditis: Use Troponin Wisely

Spallarossa

Tini

Sarocchi

et al. 2019

JCO

View full text Add to dashboard Cite

show abstract

Immune Checkpoint Inhibitor–Associated Myositis

Cited by 159 publications

References 5 publications

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors

Identification and Management of Immune Checkpoint Inhibitor–Related Myocarditis: Use Troponin Wisely

Contact Info

Product

Resources

About