SynthesisBMC medicine2015
Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis.
Synthesis in BMC medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 344 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
344 citing papers in PubMed, 6 syntheses or guidelines pooled it, 696 citations in OpenAlex.
- Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis.Frontiers in immunology · 2023Pooled it
- A Guide to Implementing Immune Checkpoint Inhibitors within a Cancer Program: Experience from a Large Canadian Community Centre.Current oncology (Toronto, Ont.) · 2022Guideline
- Ipilimumab-Induced Enterocolitis: A Systematic Review and Meta-Analysis.Drug safety · 2020Pooled it
- Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis.Oncoimmunology · 2020Pooled it
- Pooled it
- Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial.Nature medicine · 2026Trial
- Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy.Frontiers in immunology · 2025Trial
- Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction.Autonomic neuroscience : basic & clinical · 2026Review
- Immune Checkpoint Inhibitor-Related Myositis and Associated Triad Overlap Syndrome.Arthritis care & research · 2026Article
- Association of Immune Checkpoint Inhibitors With Otologic Symptoms: A Propensity Score-Matched Study.The Laryngoscope · 2026Article
- Review
- Treatment and outcomes of immunotherapy related colitis and hepatitis- a multi-centre cohort study in the United Kingdom by the National Oncology Trainee Collaborative for Healthcare Research (NOTCH).Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- VISTA neutralization by immunization reprograms immunosuppression and augments vaccine efficacy in renal carcinoma.Journal for immunotherapy of cancer · 2026Article
- Clinical features and prognosis of immune checkpoint inhibitor-associated ocular inflammation in Japanese patients: a case series.Japanese journal of ophthalmology · 2026Observational
- Review
- Immune Checkpoint Inhibitor Therapy and Acute Coronary Syndrome: A Review of Mechanisms and Management.Journal of the American Heart Association · 2026Review
- A pharmacovigilance data-driven approach to reveal high fatal adverse events following checkpoint immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Harnessing the abscopal effect: mechanistic insights and therapeutic strategies for systemic cancer immunotherapy.Frontiers in immunology · 2026Review
284 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab).
methodsA systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using R(©), package meta.
resultsOverall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included in the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently hepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-Barré syndrome, immune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 % (95 % CI, 65-79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18-30 %). The risk of developing irAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56-66 %) for ipilimumab 3 mg/kg and 79 % (95 % CI, 69-89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 % of patients. The median time of onset of irAEs was about 10 weeks (IQR, 6-12) after the onset of treatment, corresponding with the first three cycles but varied according to the organ system involved. Such immune activation could also be indicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4 blocking in 60 % of patients.
conclusionThe price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting the mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a multidisciplinary approach will help to reduce morbidity and therapy interruptions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.