Year: 2018
Type: dissertation
Study designs: Systematic Review, Meta-Analysis
Abstract: Background. Trial evidence, in adults, examining the relative effectiveness of immunosuppressive agents in the treatment of proliferative lupus nephritis (PLN) has been controversial. Trial evidence is sparse, particularly lacking long-term data, because trials are very difficult to do in this disease (due to its rarity and heterogeneous manifestations). There is no trial data to inform pediatric treatment. Observational treatment studies are limited by indication bias. A class of causal models, marginal structural models (MSMs), has been recommended in the literature to estimate treatment effectiveness using observational data, while correcting for indication bias. In order to determine the most effective immunosuppressive therapy for this disease, we designed and conducted this project. Methods. Systematic reviews and Bayesian network meta-analyses of trial evidence were performed. A MSM was used for an unbiased estimate of treatment effectiveness for childhood-onset PLN (cPLN). Results. Mycophenolate mofetil (MMF), in addition to prednisone, is the most effective therapy in the treatment of PLN, both in the short-term and long-term use, based on current evidence. Our pediatric findings were consistent with adult evidence and suggestive of MMF's superiority over other agents. Tacrolimus seemed better than MMF for adults in inducing renal remission at 6 months, but it has been insufficiently examined in other geographical regions than Asia. The probability of inducing renal remission for the best therapy was about 50% or lower at 6 months. Interestingly, the probability of preventing renal death at 2--3 years for azathioprine used at the current dose was second only to MMF. The 6% improvement in renal function, on average over a period of about 4 years in cPLN, induced by MMF versus other immunosuppressive agents (while correcting for indication bias) was statistically significant (p = 0.02). Conclusions. Whereas the evidence may not be sufficient to be definitive, MMF appears to be the best treatment for PLN. More studies are needed. Future clinical trials need to use a standardized conduct protocol and have a longer study duration. Future observational treatment studies should consider using MSM, especially for children and youth for rare diseases where clinical trials are infeasible.
Source: TSpace (University of Toronto)
Author: Yu Tian
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3147301232