Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm

Klair, Jagpal S.; Girotra, Mohit; Hutchins, Laura F.; Caradine, Kari D.; Aduli, Farshad; Garcia‐Saenz‐de‐Sicilia, Mauricio

doi:10.1007/s10620-016-4042-4

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…An example is the common use of TNF antagonists to treat the colitis associated with ICI therapy. 31 The optimum dosage of corticosteroids is also uncertain as some patients in our series required doses as high of 120 mg of prednisone daily for relief of their symptoms, while others could be maintained on a much lower dose after an initial high dose. Collaboration between rheumatologists and oncologists will be instrumental to understand the spectrum of rheumatological IRAEs and their treatment.…”

Section: Discussionmentioning

confidence: 94%

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

et al. 2016

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Objectives Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. Methods We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. Results We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. Conclusions As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.

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Section: Discussionmentioning

confidence: 94%

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

et al. 2016

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“…For other IRAE, like colitis, pneumonitis, dermatologic manifestations, and hepatitis, treatment recommendations have been developed based on clinical experience 15,45 . These treatment algorithms give recommendations based on the grade of adverse event about treating with corticosteroids, TNF-inhibitors, and holding or stopping the ICI.…”

Section: Treatment Considerationsmentioning

confidence: 99%

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Cappelli

Shah²,

Bingham³

2017

Rheumatic Disease Clinics of North America

107

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Summary Immune checkpoint inhibitors (ICIs) are being increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAE). Some IRAE including inflammatory arthritis, sicca syndrome, myositis and vasculitis are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.

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“…Of the 1892 unique studies identified using our search criteria, 61 studies fulfilled our inclusion criteria and were included in the qualitative analysis (38 full text articles, 23 in abstract form) . Results of our search strategy are depicted in Figure .…”

Section: Resultsmentioning

confidence: 99%

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

Wright

Piper

Bishu

et al. 2019

Aliment Pharmacol Ther

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Summary Background Immune checkpoint inhibitors are used in the treatment of multiple advanced stage cancers but can induce immune‐mediated colitis necessitating treatment with immunosuppressive medications. Diagnostic colonoscopy is often performed but requires bowel preparation and may delay diagnosis and treatment. Sigmoidoscopy can be performed rapidly without oral bowel preparation or sedation. Aims Characterize the colonic distribution of immune‐mediated colitis to determine the most efficient endoscopic approach. Methods A systematic review of checkpoint inhibitor‐induced colitis case reports and series was conducted in both PubMed and Embase through 3 January 2017. A single centre retrospective chart review of patients who underwent endoscopic evaluation for diarrhoea after treatment with a checkpoint inhibitor (ipilimumab, nivolumab or pembrolizumab) between 1 January 2011 and 3 January 2017 was performed. Clinical, endoscopic and histologic data were collected. Results A detailed systematic review resulted in 61 studies, in which 226 cases of colitis were diagnosed by lower endoscopy (125 colonoscopy, 101 sigmoidoscopy). Only four patients had isolated findings proximal to the left colon. In our centre, 31 patients had histologic features of checkpoint inhibitor‐induced colitis, for which 29 patients had complete data. The left colon was involved in all cases. Sigmoidoscopy would be sufficient to diagnose >98% of reported cases of checkpoint inhibitor‐mediated colitis diagnosed by lower endoscopy. Conclusions Moderate to severe checkpoint inhibitor‐induced colitis involves the left colon in the majority of cases (>98%). Sigmoidoscopy should be the initial endoscopic procedure in the evaluation of this condition.

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Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm

Cited by 16 publications

References 43 publications

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

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