Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy

Abstract

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m²: 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m²: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m² during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m² did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.

Keywords: IgA nephropathy; glomerular disease; glomerulonephritis; immunosuppression.

Figure 1.

A total of 162 patients who had completed the 6-mo run-in phase of STOP-IgAN participated in the subsequent 3-yr trial phase. One hundred and nine of them had a GFR of at least 60 ml/min/1.73 m² and 53 of them had a GFR between 30 and 59 ml/min/1.73 m². These patients were randomly assigned to either continue supportive care or receive additional immunosuppression.

Figure 2.

Primary end points in the two GFR subgroups of STOP-IgAN. Panel A shows the first primary end point: full clinical remission at the end of the 3-year trial phase (i.e. urinary protein-to-creatinine ratio <0.2 g/g and a GFR-loss <5 ml/min/1.73 m²). Panel B shows the second primary end point: a GFR decrease of at least 15 ml/min/1.73 m² during the trial phase. Analyses were performed for both end points with the use of a full analysis set and an available-case analysis set. 97.5% CI, 97.5% confidence interval.