Quarter in review – Clinical Science

V A Deepika Ponnuru MD, DM (Rheumatology)
Consultant Rheumatologist, Manipal Hospitals, Vijayawada, Andhra Pradesh

Study in focus 1: Effectiveness of Cyclophosphamide versus Rituximab based remission induction in ANCA associated vasculitis (AAV) for the risk of kidney failure and mortality.

Renal failure and death in AAV,the long-term outcomes which are not frequently reported in clinical trials were addressed in this study. Patients treated with cyclophosphamide (CYC) or Rituximab for remission induction were compared retrospectively in a real-world mass general Brigham AAV cohort. It included 595 patients with anti-PR-3(30%) and anti -MPO ANCA positivity (70%), diagnosed between 2002 and 2019. Mean age was 61 years, renal involvement (baseline median eGFR 37.3ml/min/1.73 m2) was observed in 69%. Rituximab based induction was received in 60%, CYC in 40% of the study population.

A total of 133 events (kidney failure and death) were recorded at 5 years and incidence rates in Rituximab and cyclophosphamide-based regimens were 6.8(95% CI 5.30-8.30) and 6.1(95% CI 4.50-7.70) respectively per 100 person-years. The presence of renal involvement, severe renal or major organ involvement were similar between the two groups at 1,2 and 5 years. At 5 years, both the regimens had similar risk of renal failure and death in multivariable adjusted analysis (HR 1.03 [95%CI 0.55-1.93]) and in propensity score matched analysis (HR 1.05 [95%CI 0.55-1.99]).  Patients who were on Rituximab based treatment tapered steroids to <5mg/day within 6 months of initiation compared to CYC and risk of severe infections (requiring hospitalization or causing death) were similar in both the regimens.

This study emphasizes that Rituximab and Cyclophosphamide have similar long-term risk of renal failure, severe infections and death.

Study in focus 2: Efficacy and safety of immunosuppressive agents for adults with lupus nephritis: a systematic review and network meta-analysis

The study conducted a systematic review and network meta-analysis to evaluate the efficacy and safety of various immunosuppressive agents in the management of lupus nephritis (LN), a severe complication of systemic lupus erythematosus. The analysis included 62 randomized controlled trials (RCTs) comprising 6,936 patients treated with 20 different regimens. The primary outcomes assessed were total remission rate, complete remission rate, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.

The results indicated that the combination of tacrolimus (TAC) or voclosporin (VCS) with mycophenolate mofetil (MMF) and glucocorticoids (GC) demonstrated the highest total and complete remission rates. TAC plus GC emerged as the optimal single-agent immunosuppressive regimen, exhibiting superior therapeutic effects and a lower incidence of adverse events. Other findings included mycophenolate-based regimens being effective in preventing relapse, all-cause mortality, and ESRD, while azathioprine plus cyclophosphamide plus GC showed the lowest risk of infection. However, this result be due to change owing to smaller number of included trials which reported infection risk with AZA plus CYC plus GC.

Despite these findings, several limitations were acknowledged, such as the lack of stratified data, varying doses of immunosuppressive agents, and potential publication bias. 

In conclusion, this comprehensive analysis provides valuable insights into the comparative efficacy and safety of immunosuppressive agents for LN. The study recommends further large-scale RCTs to directly compare these agents and improve the understanding of their differential effects in the treatment of LN.


  1. Wallace ZS, Fu X, Cook C, Ahola C, Williams Z, Doliner B et al. Comparative Effectiveness of Rituximab – Versus Cyclophosphamide-Based Remission Induction Strategies in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the Risk of Kidney Failure and Mortality. Arthritis Rheumatol. 2023;75(9):1599-1607.
  2. Jiang N, Jin S, Yu C, Zhao J, Wang Q, Tian X, Li M, Zeng X. Efficacy and safety of immunosuppressive agents for adults with lupus nephritis: a systematic review and network meta-analysis. Front Immunol. 2023;14:1232244.