Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: Systematic review and meta-analysis Journal Article


Authors: Baxi, S.; Yang, A.; Gennarelli, R. L.; Khan, N.; Wang, Z.; Boyce, L.; Korenstein, D.
Article Title: Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: Systematic review and meta-analysis
Abstract: Objective To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Study selection Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Data extraction Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. Results 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Conclusions Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common. © 2018 Published by the BMJ Publishing Group Limited.
Keywords: treatment response; overall survival; fatigue; review; hepatitis; diarrhea; drug targeting; carboplatin; myalgia; cetuximab; risk assessment; arthralgia; backache; pneumonia; rash; arthritis; colitis; hypothyroidism; pemetrexed; everolimus; musculoskeletal disease; biological product; programmed death 1 ligand 1; programmed death 1 receptor; randomized controlled trial (topic); meta analysis (topic); hypophysitis; musculoskeletal pain; systematic review (topic); nivolumab; human; priority journal; pembrolizumab; atezolizumab; malignant neoplasm
Journal Title: BMJ: British Medical Journal (International Edition)
Volume: 360
ISSN: 0959-8146
Publisher: BMJ Publishing Group Ltd.  
Date Published: 2018-03-14
Start Page: k793
Language: English
DOI: 10.1136/bmj.k793
PUBMED: 29540345
PROVIDER: scopus
PMCID: PMC5851471
DOI/URL:
Notes: Review -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Shrujal S Baxi
    69 Baxi
  2. Lindsay Marie Boyce
    4 Boyce
  3. Annie   Yang
    5 Yang
  4. Niloufer Khan
    7 Khan