Clinical trial NCT04898751: Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors
Official title: Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cutaneous Toxicity From ICI Therapy
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2021-05-24
Enrollment: 2214
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with an immune checkpoint inhibitor for cancer.

Brief summary: Immune checkpoint inhibitors (ICIs) are associated with a wide variety of cutaneous immune-related adverse events (cirAEs). These cirAEs are reported to be the most common immune-related adverse events (irAEs) and the first to appear. This study examines the appearance of cirAEs within the World Health Organization (WHO) pharmacovigilance database, VigiBase.

Detailed description: ICIs have revolutionized clinical oncologic care. The ICIs that are currently FDA approved fall into three main categories: those that block the cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4; ipilimumab), block the programmed cell death protein-1 (anti-PD-1; nivolumab, pembrolizumab, cemiplimab), and block the programmed cell death ligand-1 (anti-PD-L1; atezolizumab, avelumab, durvalumab) pathway. There is a considerable diversity of cirAEs that have been reported with these ICIs in both monotherapy and combination therapy.

VigiBase is the WHO pharmacovigilance database that monitors individual case safety reports associated with certain drugs. The largest database of its kind in the world, VigiBase is managed by the Uppsala Monitoring Center (UMC) in Sweden, and since its inception in 1967 has received over 19 million individual case safety reports (ICSRs) from over 130 contributing countries. In this study, the investigators examine the appearance of cutaneous immune related adverse events in the setting of immunotherapy within VigiBase.

Eligibility criteria: Inclusion Criteria:

* Treated with either Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).
* Developed an adverse reaction that was submitted to a pharmacovigilance center and was determined to be related to aforementioned immune checkpoint inhibitors.
* Adverse reaction was determined to be within the System Organ Class (SOC) "Skin and subcutaneous disorder".

Exclusion Criteria:

* Adverse event was determined not to be immune-related (for example, infectious etiology) or was a symptom (e.g., edema).
* Adverse event developed before the administration of ICI.

Primary outcomes:
measure: Cutaneous toxicity of ICIs
timeFrame: From 01/01/2008 to 08/31/2020
Secondary outcomes:
measure: Reporting odds ratio for monotherapy vs combination therapy
timeFrame: From 01/01/2008 to 08/31/2020
measure: Reporting odds ratio for differing monotherapy
timeFrame: From 01/01/2008 to 08/31/2020
measure: Co-occuring irAEs
timeFrame: From 01/01/2008 to 08/31/2020
measure: Disproportionality assessment of cirAEs with ICIs
timeFrame: From 01/01/2008 to 08/31/2020
measure: Indication
timeFrame: From 01/01/2008 to 08/31/2020
measure: Time to onset
timeFrame: From 01/01/2008 to 08/31/2020
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Care Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Shawn Kwatra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Le TK, Brown I, Goldberg R, Taylor MT, Deng J, Parthasarathy V, Bordeaux ZA, Alphonse MP, Kwatra MM, Naranbhai V, Gusev A, Alhariri J, LeBoeuf NR, Reynolds KL, Cappelli LC, Naidoo J, Brahmer JR, Kang S, Semenov YR, Kwatra SG. Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. J Invest Dermatol. 2022 Nov;142(11):2896-2908.e4. doi: 10.1016/j.jid.2022.04.020. Epub 2022 May 20.