Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Patients consider common side effects of medications prominently in treatment decision-making. To our knowledge, with the exception of a Cochrane review that analyzed data up to April 2012, limited or no information exists on comparisons of common, non-fatal side effects of immunosuppressive medications used for the treatment of lupus nephritis. Our objective was to perform an up to date systematic review and network meta-analysis (NMA) to compare harms/safety of cyclophosphamide (CYC) and mycophenolate mofetil (MMF) for the treatment of lupus nephritis.
Methods
Cochrane and ACR librarians performed an updated search for immunosuppressive medications for lupus nephritis up to September 2013 updating the data from the systematic review that formed the basis of the 2012 ACR lupus nephritis treatment recommendations and the published Cochrane Review. We abstracted safety data related to the following harms/adverse events (AEs): alopecia, nausea, ovarian failure, endocrine AEs, cytopenia and leucopenia. Bayesian network meta-analyses (NMA) were conducted. A binomial likelihood model, which allows for the use of multi-arm trials was used. Informed priors were assigned for basic parameters and odds ratios, as well as risk ratios and risk differences, and 95% credible intervals were modeled using Markov chain Monte Carlo methods. Brooks-Gelman-Rubin plots were used to assess model convergence. Model fit was examined using the deviance information criterion (DIC) and the residual deviance. The degree of inconsistency was assessed by comparing statistics for the deviance and deviance information criterion in fitted consistency and inconsistency models. In further sensitivity analyses, fixed effects models and models using vague priors were also conducted.
Results
Compared to MMF, CYC was associated with higher risk of alopecia by almost 4-fold, leucopenia by 3-fold and ovarian failure by 6-fold (Table 1). The higher risk of cytopenia with CYC almost reached statistical significance (Table 1). The risk of nausea and endocrine side effects did not differ significantly between CYC and MMF. Risk differences between CYC and MMF are provided in Table 1.
Conclusion
Conclusions: Our systematic review and meta-analysis identified several important differences between the harms of CYC and MMF in patients with lupus nephritis. These findings provide clinicians and patients with the magnitude of differences in these common side effects and can help patients with treatment decision-making.
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Table 1: Comparison of cyclophosphamide (CYC) vs. mycophenolate mofetil (MMF) |
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Comparison |
RR (95% CI) |
Risk Difference (95% CI) |
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Alopecia, CYC vs. MMF |
3.69 (1.77, 6.86) |
17.16 (4.79, 34.94) |
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Nausea, MMF vs. CYC |
0.37 (0.14, 1.10) |
-2.32 (-10.86,0.27) |
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Endocrine AEs*, CYC vs. MMF |
1.52 (0.70, 3.42) |
2.04 (-1.72, 8.58) |
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Cytopenia, CYC vs. MMF |
1.62 (0.99, 2.76) |
8.58 (-0.13, 19.77) |
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Leucopenia, CYC vs. MMF |
2.82 (1.63, 4.64) |
9.24 (3.48, 17.13) |
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Peto’s odds ratio (95% CI) |
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Ovarian failure, CYC vs. MMF |
6.36 (2.59, 15.63) |
— |
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*Diabetes and hyperglycemia; significant odds ratios are in bold |
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Disclosure:
J. A. Singh,
Savient,
2,
Takeda,
2,
Degeneron,
5,
Allergan ,
5;
A. Kotb,
None;
A. Hossain,
None;
G. A. Wells,
Novartis, Bristol- Myers Squibb, and Abbott,
5,
Bristol-Myers Squibb,
2,
speaker honorariums from Abbott;,
8,
He is a member of the executive of OMERACT and of the Scientific Committee for the Ontario Biologics Research Initiative,
9.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-systematic-review-and-network-meta-analysis-of-cyclophosphamide-and-mycophenolate-mofetil-in-lupus-nephritis/