Assessing Lupus Nephritis Remission Rates After Use of Immunosuppressive Agent Combinations

A meta-analysis published in Frontiers of Immunology found that for adults with lupus nephritis, a combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) demonstrated the greatest improvement in total remission rate compared with other combination immunosuppressive regimens.

The researchers analyzed data from 62 randomized clinical trials, reported in 172 studies. A total of 6936 patients were included. Sample sizes ranged from 15 to 446 patients, and 37 of the trials were multicenter. Induction therapy was assessed in 44 trials, maintenance therapy was assessed in 7 trials, and the remaining 11 trials assessed both induction and maintenance. Follow-up ranged from 10.0 weeks to 92.4 months.

The study population was treated with 20 categories of treatment regimens. The primary outcome was total remission rate. Secondary outcomes were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer. Effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA).

Total, Complete Remission Rates

Regarding the primary outcomes, the combination of TAC, MMF, and GC led to the greatest rate of total remission (SUCRA, 86.63%) compared with all other regimens. Ocrelizumab (OLB) plus GC showed the lowest total remission (SUCRA, 6.47%). The following regimens demonstrated a SUCRA for total remission >70%:

• Azathioprine (AZA), cyclophosphamide (CYC), and GC (71.5%)
• Abatacept (ABA), AZA, CYC, and GC (74.84%)
• Belimumab (BLM), MMF/CYC, and GC (74.68%)
• OLB, MMF, and GC (80.89%)
• CYC, MMF/AZA/leflunomide (LEF), and GC (81.42%)
• Voclosporin (VCS), MMF, and GC (85.05%)

Compared with GC as a single agent, the odds ratios (ORs) for total remission were highest for the following regimens:

• ABA, AZA, CYC, and GC (OR, 6.89; 95% CI, 2.19-21.68)
• AZA, CYC, and GC (OR, 6.82; 95% CI, 2.73-17.03)
• BLM, MMF/CYC, and GC (OR, 7.04; 95% CI, 3.05-16.28)
• CYC, MMF/AZA/LEF, and GC (OR, 7.72; 95% CI, 3.67-16.25)
• Obinutuzumab (OTB), MMF, and GC (OR, 8.21; 95% CI, 3.54-19.08)
• TAC, MMF, and GC (OR, 9.04, 95% CI, 5.13-15.92)
• VCS, MMF, and GC (OR, 8.33; 95% CI, 4.76-14.56)

The combination of VCS, MMF, and GC gave the best improvement in complete remission (SUCRA, 90.71%).

Safety Outcomes

The lowest risk of relapse was found for the combination of CYC, MMF, and GC (SUCRA, 85.57%); this combination was also associated with the lowest risk of cancer (SUCRA, 85.14%). OTB, MMF, and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%).

Rituximab (RTX) plus MMF and GC demonstrated the greatest benefit regarding risk of ESRD (SUCRA, 83.11%). Risk of infection was lowest with AZA, CYC, and GC (SUCRA, 68.59%).

In summary, the authors wrote, “Our study found that TAC plus MMF plus GC provided the best therapeutic effect in terms of the total remission rate and SLEDAI.” They added that “MMF-based regimens, such as MMF plus CYC plus GC, OTB plus MMF plus GC, and RTX plus MMF plus GC, were optimal for preventing relapse, all-cause mortality, and ESRD.”