TY - JOUR
T1 - Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy
T2 - The TESTING Randomized Clinical Trial
AU - Lv, Jicheng
AU - Zhang, Hong
AU - Wong, Muh Geot
AU - Jardine, Meg J.
AU - Hladunewich, Michelle
AU - Jha, Vivek
AU - Monaghan, Helen
AU - Zhao, Minghui
AU - Barbour, Sean
AU - Reich, Heather
AU - Cattran, Daniel
AU - Glassock, Richard
AU - Levin, Adeera
AU - Wheeler, David
AU - Woodward, Mark
AU - Billot, Laurent
AU - Chan, Tak Mao
AU - Liu, Zhi Hong
AU - Johnson, David W.
AU - Cass, Alan
AU - Feehally, John
AU - Floege, Jürgen
AU - Remuzzi, Giuseppe
AU - Wu, Yangfeng
AU - Agarwal, Rajiv
AU - Wang, Hai Yan
AU - Perkovic, Vlado
AU - TESTING Study Group
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Importance: Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.Objective: To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.Design, Setting, and Participants: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.Interventions: Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.Main Outcomes and Measures: The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.Results: After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).Conclusions and Relevance: Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.
AB - Importance: Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.Objective: To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.Design, Setting, and Participants: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.Interventions: Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.Main Outcomes and Measures: The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.Results: After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).Conclusions and Relevance: Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.
UR - http://www.scopus.com/inward/record.url?scp=85027500963&partnerID=8YFLogxK
U2 - 10.1001/jama.2017.9362
DO - 10.1001/jama.2017.9362
M3 - Article
C2 - 28763548
AN - SCOPUS:85027500963
SN - 0098-7484
VL - 318
SP - 432
EP - 442
JO - JAMA: Journal of the American Medical Association
JF - JAMA: Journal of the American Medical Association
IS - 5
ER -
