Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study

Abstract

BackgroundCurrent guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care.MethodsRetrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge.ResultsThirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15–25) in the rapid-taper group compared with 38 days (IQR 30–58) in the standard-of-care group. There was no significant difference in the time to renal recovery between the groups, though numerically higher numbers of patients recovered by 30 days, 11 (85%) in the rapid-taper arm versus 6 (46%) in the standard of care arm. Exposure to other nephritis-causing medications (proton pump inhibitor or trimethoprim-sulfamethoxazole) during the corticosteroid taper was more common in the standard of care group, 9 (64%) versus rapid-taper group, 2 (15%), and was associated with longer time to renal recovery, 20 days (IQR 14–101) versus 13 days (IQR 7–34) in those that discontinued nephritis-causing medications. Fifteen (56%) of patients were rechallenged with ICIs, and only two (13%) developed recurrent nephritis.ConclusionsPatients with ICI-induced nephritis have excellent kidney outcomes when treated with corticosteroids that are tapered over 3 weeks.

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

“…Lee et al examined outcomes among 13 patients with ICPi-AKI treated with a short duration of CS (tapered to ≤10 mg daily of prednisone equivalents within 3 weeks) versus 14 patients treated with a longer duration of CS, and found no significant difference in the time to renal recovery between groups. 8 Our data are consistent with these findings and expand on them in a larger and more generalizable cohort.…”

Immune checkpoint inhibitors and kidney disease

“…Most studies have shown a relatively low risk of recurrence of ICI-associated AKI 16∼23% with ICI-rechallenge. Although this risk is low, it is important to note that patients are also at risk of developing another severe irAE in a different organ system [26 ▪ ]. Ultimately, the decision to rechallenge a patient with ICI is determined by their oncologist and is driven by the tumour's sensitivity to ICI, the patient's current response to therapy, the duration of ICI treatment prior to the ICI-induced AKI, the presence or absence of good alternative second-line therapies and patient preference.…”

Expert Clinical Management of Severe Immune-Related Adverse Events: Results from a Multicenter Survey on Hot Topics for Management

“…A recent retrospective study suggested that the responses of ICI-induced nephritis were similar with rapid and standard corticosteroid tapering, an approach that can limit the secondary adverse events associated with long-term steroid regimens. Lee et al [ 22 ] showed that patients with ICI-induced nephritis have excellent kidney outcomes when given corticosteroids tapered rapidly over 3 weeks. In our survey, about half of the experts favored tapering over 4–6 weeks, whereas 25% selected a longer period of 12 weeks.…”