In patients with lupus nephritis (LN), intensified B-cell depletion induction therapy (IBCDT) without further immunosuppressive maintenance therapy is as effective as conventional mycophenolate mofetil (MMF) or cyclophosphamide (CYC) regimens with immunosuppressive maintenance therapy, according to investigators.
Dario Roccatello, MD, of the University of Turin and S. Giovanni Bosco Hospital in Turin, Italy, and collaborators compared outcomes from 3 LN regimens: add-on IBCDT in 30 patients, MMF plus methylprednisolone in 20 patients, and CYC plus methylprednisolone in 10 patients. Patients in the latter 2 groups served as controls and were matched to the IBCDT patients by age, sex, LN class, and indication for treatment. The IBCDT protocol involved 4 weekly rituximab 375 mg/m2 doses and 2 additional doses after 1 and 2 months; 2 infusions of 10 mg/kg CYC; and 3 methylprednisolone pulses, followed by oral prednisone (tapered to 5 mg/d by the third month). No immunosuppressive maintenance therapy was given.
The 20 patients in the methylprednisolone plus MMF arm received 3 methylprednisolone pulses over 3 days followed by oral prednisone and MMF 2-3 g/d. The 10 patients in the CYC group received the methylprednisolone pulses, followed by prednisone and 1 infusion of CYC every 2 weeks for 6 total doses. In these respective control groups, immunosuppressive maintenance therapy consisted of continued MMF or azathioprine with prednisone for more than 3 years.
Complete peripheral blood B-cell depletion was achieved in all patients who received IBCDT, Dr Roccatello’s team reported in Kidney International Reports. At 12 months, complete renal response (CRR), defined as proteinuria less than 0.5 g/24 h and near-normal eGFR, had been achieved in 28 (93%) patients treated with IBCDT, 13 (65%) on MMF, and 7 (70%) on CYC. IBCDT was significantly associated with a higher CRR compared with the other regimens.
The time to CRR, however, did not differ among the 3 groups. Partial renal response (a 50% or greater reduction in proteinuria to subnephrotic levels and near normal eGFR) occurred in 2 (7%) patients treated with IBCDT, in 4 patients on MMF (20%), and in 3 patients (30%) on CYC. No response was observed in 3 patients on MMF (15%).
Steroid-sparing occurred with IBCDT, the investigators also reported. The oral prednisone dose was significantly lower in the IBCDT group than in the MMF or CYC group: mean 2.9 vs 10.5 vs 7.5 mg/d.
Over a mean follow-up duration of 44 to 48 months, the team observed no significant differences in proteinuria, serum creatinine, or new flares among groups.
Systemic lupus erythematosus activity index, anti-double‐stranded DNA antibody, C3/C4 complement levels, and erythrocyte sedimentation rate were not significantly different among groups at 12 months.
With respect to safety, none of the patients in the IBCDT group had severe adverse events, severe infection, hypoalbuminemia, or moderate to severe hypogammaglobulinemia. Significantly more patients in the 2 control groups than in the IBCDT group developed glaucoma related to glucocorticoid use: 23% vs 3%.
“While a large scale RCT is warranted to confirm our findings, in this prospective study we showed that the IBCDT regimen is at least as effective as MMF or CYC pulses in inducing remission in patients with active LN… This approach prevented prolonged immunosuppression and remarkably reduced the risk of steroid-related adverse effects,” Dr Roccatello’s team concluded.
Roccatello D, Sciascia S, Naretto C, et al. A prospective study on long-term clinical outcomes of patients with lupus nephritis treated with an intensified B-cell depletion protocol without maintenance therapy. Published February 2, 2021. Kidney Int Rep. doi:10.1016/j.ekir.2021.01.027