Infliximab for the Treatment of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury

Inclusion Criteria

• Age ≥ 18 years
• Acute kidney injury (AKI), defined as ≥ 1.5-fold increase in serum creatinine (SCr) compared to baseline. Baseline is defined as the closest SCr prior to ICI initiation
• Receipt of ICI in the 180 days preceding AKI onset
• AKI due to ICI-acute interstitial nephritis (AIN), based on either a kidney biopsy or clinical adjudication by the treating team
• Ability of the patient to understand the study and willingness to sign the written informed consent form

Exclusion Criteria

• Any condition other than ICI-AKI requiring high dose GCs (> 10 mg/day prednisone equivalents) or other immunosuppressants, such as infliximab, tocilizumab, mycophenolate mofetil, B cell depletion, or calcineurin inhibitors, within 14 days preceding screening
• Evidence of any uncontrolled infection, including tuberculosis (must have no evidence of active or latent tuberculosis [TB] determined by clinical history and negative interferon gamma release assay within the last 12 months or at screening); hepatitis B (based on hepatitis B surface antibody [antiSAg] and hepatitis B virus [HBV] deoxyribonucleic acid [DNA] negative within the last 12 months or at screening. Patients with isolated hepatitis B core antibody (anti-HBcore) positivity must agree to antiviral prophylaxis with entecavir for 6 months after receiving infliximab); hepatitis C (must have no uncontrolled active infection evidenced by negative hepatitis C virus (HCV) antibody or HCV ribonucleic acid (RNA) within the last 12 months or at screening, and reflex testing must be performed for any patient with HCV antibody positivity); patients with known human immunodeficiency virus (HIV) must be on stable disease antiretroviral therapy ≥ 12 weeks with a negative viral load [< 50 copies/mL] at screening and CD4 count ≥ 350 cells/uL) measured within the last 12 months
• History of hypersensitivity to infliximab or murine proteins
• Moderate–severe (New York Heart Association class III/IV) heart failure or recent decompensation
• Any active or uncontrolled hepatitis (immune-mediated, viral, or drug-induced) defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) or total bilirubin > 1.5 × ULN in the 14 days preceding screening. (Participants with Gilbert syndrome can be enrolled with elevated total bilirubin if their direct bilirubin is not > ULN)
• History of demyelinating disease (e.g., multiple sclerosis) or optic neuritis
• Uncontrolled or recurrent serious infections (e.g., untreated abscess, active sepsis), requirement for oral or intravenous antibiotics, at screening
• Receipt of any live vaccine in the 28 days preceding screening
• Kidney biopsy showing primary lesion other than acute interstitial nephritis
• Life expectancy < 12 weeks in the opinion of the investigator
• Unable to tolerate study procedures, including IV insertion
• Contraindication to GCs, including but not limited to, uncontrolled diabetes mellitus with inability to safely manage expected steroid-induced hyperglycemia, severe and active psychiatric disease requiring ongoing titration of psychiatric medications, active peptic ulcer disease, severe osteoporosis or high fracture risk, or other investigator-determined conditions where systemic GC or infliximab would pose unacceptable risk in the judgment of the investigator
• Vulnerable populations including children, prisoners, neonates and pregnant or breastfeeding patients