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John H. Kempen, Craig W. Newcomb, Robert B. Nussenblatt, James T. Rosenbaum, Eric B. Suhler, Jennifer E. Thorne, C Stephen Foster, Douglas A. Jabs, Grace A. Levy-Clarke, Marshall M. Joffe; Methotrexate vs. Mycophenolate Mofetil for Ocular Inflammatory Diseases. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4169.
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To compare the effectiveness of methotrexate (MTX) vs. mycophenolate mofetil (MMF) for ocular inflammatory diseases.
Marginal structural models (MSM) are useful in observational datasets to model the effect of a treatment which changes over time while accounting for time-varying confounding variables and informative censoring. MSM uses a statistical weighting procedure to partially mimic a randomized trial and create balance on observed covariates between subjects receiving different levels of treatment at different times. We used MSM to compare MMF vs. MTX for non-infectious inflammatory eye disorders. The primary outcome was "corticosteroid-sparing" (complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days), evaluated using survival analysis with stabilized MSM-derived weights. Retrospective cohort data came from 613 patients managed at four tertiary uveitis centers, who were taking MTX or MMF and no other immunosuppressants.
After adjusting for confounding by baseline and time-varying covariates, the incidence of corticosteroid-sparing success was lower for MTX than MMF (HR=0.65, 95% confidence interval (CI): 0.44-0.95; see Figure). Corticosteroid-sparing was achieved in less than 6 months for about two-thirds of MMF-treated cases, but sometimes treatment success took more than a year. We did not find substantial variation in the effect of treatment (MMF vs. MTX) by site of inflammation (anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, MMP, or other sites of ocular inflammation). The rate of discontinuation of therapy was similar in the two groups.
The results suggest that, on average, MMF is superior to MTX for ocular inflammatory diseases, with faster achievement of corticosteroid-sparing, and a higher proportion having achieved corticosteroid-sparing success at every point in time between about 1.5 months and two years. The onset of effect took months even in the MMF-treated group. Results are weighted to account for censoring, and reflect what would have happened had patients not stopped their treatment.
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