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Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review

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Abstract

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunological AEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16 mg daily for 22 days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that the consequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.

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The datasets generated during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Faculty of Medicine, Clinical Hospital Center Rijeka, Department of Rheumatology and Clinical Immunology, University of Rijeka, Rijeka, Croatia

    Tatjana Zekić

  2. Department of Pharmacology, Clinical Hospital Center Rijeka, Rijeka, Croatia

    Mirjana Stanić Benić

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All co-authors (TZ, MSB) contributed to the design of the work and revised it critically for important intellectual content; they approved the final version to be published. All co-authors are fully responsible for the integrity and accuracy of all aspects of the work.

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Correspondence to Tatjana Zekić.

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Zekić, T., Benić, M.S. Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review. Rheumatol Int 43, 559–565 (2023). https://doi.org/10.1007/s00296-022-05247-5

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