Effectiveness and Safety of Allopurinol, Febuxostat, and Rasburicase in the Prevention of Tumor Lysis Syndrome: A Systematic Review and Network Meta-analysis

Abstract

Although prevention is vital in managing tumor lysis syndrome (TLS), no study directly compares various regimens. This study compared the effectiveness and safety of urate-lowering agents in preventing TLS. Databases were searched for randomized controlled trials involving adults with hematologic or solid malignancies on chemotherapy or cytoreductive agents given allopurinol, febuxostat, or rasburicase alone or in combination at any dose, form, or frequency published in English by December 2021. Outcomes included laboratory and clinical TLS expressed as relative risks, adverse events as described by authors, and mean serum uric acid (sUA) as mean differences of area under the curve. A network of meta-analysis and post-hoc meta-analysis based on TLS risk using a random-effects model was done using Stata 14.0 and Review Manager 5.3, respectively. Certainty of evidence was assessed using the GRADE approach. Three studies with a total of 633 participants given allopurinol, febuxostat, rasburicase, or rasburicase combined with allopurinol were included. Rasburicase is more effective than allopurinol in preventing laboratory TLS (relative risk: 0.51; 95% confidence interval [CI]: 0.32–0.81) based on moderate quality evidence. No significant differences were observed in clinical TLS. Adverse events were attributable to toxicities of chemotherapy. Rasburicase alone or in combination with allopurinol was better than allopurinol or febuxostat alone in reducing sUA level. Febuxostat is more effective than allopurinol in lowering sUA levels among patients at high-risk of TLS (mean difference −125.75; 95% CI: −223.47 to −28.02). Rasburicase may be the most effective agent in preventing laboratory TLS and maintaining low sUA levels.

Rasburicase in treating tumor lysis syndrome: An umbrella review

“…Concerning economic outcomes, single-dose rasburicase was the most cost-efficient. 3 Masamayor et al., 2022 35 PubMed, the Cochrane Library, and Clinicaltrials.gov Inception till December 2021 Participants: 633 K = 3 RCT (3) RoB: Cochrane Risk of Bias Assessment tool Allopurinol, febuxostat, or rasburicase alone or in combination Comparison: intravenous hydration with crystalloid solutions and sodium bicarbonate Incidence of laboratory and clinical TLS; Adverse events Serum uric acid levels Rasburicase was more effective in preventing laboratory TLS than was allopurinol (RR = 0.74 (95% CI = 0.17–3.22). Rasburicase was the most effective agent in preventing laboratory TLS and maintaining low serum uric acid levels compared to the effects of allopurinol (MD = −569, 95% CI = −796.38 to −341.62) and febuxostat (MD = −426.08, 95% CI = −702.64 to −149.51).…”

“…Three reviews discussed study heterogeneity, 31 , 33 , 38 , and the source of conflict was declared in five of the included reviews. 32 , 33 , 35 , 37 , 39 Table 2 illustrates the quality appraisal using AMSTAR 2.…”

“…Three reviews compared the efficacy of rasburicase with allopurinol 31 , 34 , 38 in reducing TLS outcomes, and one review explored the efficacy of urate oxidase, including rasburicase, with intravenous hydration using crystalloid solutions and sodium bicarbonate on TLS outcomes. 35 …”

“…The results of RCTs on the development of TLS are contradictory. Two reviews reported that rasburicase, as compared to allopurinol, has a significant effect on the development of TLS among patients (risk ratio [RR] = 0.74, 95% CI = 0.17–3.22; 35 OR = 4.06, 95% CI = 3.11–5.28), 39 while two reviews reported no difference in the incidence of TLS (RR = 0.74, 95% CI = 0.17–3.20; 31 RR = 0.77, 95% CI = 0.44–1.33). 38 The meta-analysis exploring the difference in the efficacy between rasburicase and allopurinol excluded a study by Feng et al.…”

“…RCTs and clinical controlled trials indicated that rasburicase had a significant main effect on reducing and maintaining serum uric acid levels compared to the effects of allopurinol (mean difference [MD] = −569 mg/dL, 95% CI = [−796.38,−341.62] mg/dL 35 ; MD = −201.00 mg/dL, 95% CI = [−258.05, −143.95] mg/dL 38 ; MD = −19.96 mg/dL, 95% CI = [–22.43,–17.49] mg/dL 39 ). Observational studies reported that 93.4% of patients achieved normal serum uric acid levels, 31 and 6 mg and 0.15 mg/kg doses of rasburicase were most effective in serum uric acid reduction, with a mean reduction of 8.45 mg/dL (95% CI = 7.51–9.38 mg/dL) and 10 mg/dL (95% CI = 8.58–11.42 mg/dL), respectively.…”