Dataset Information

Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials.

ABSTRACT: OBJECTIVE:To assess the efficacy of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on modified Rodnan skin score (MRSS) in participants enrolled in the Scleroderma Lung Study (SLS) I and II. METHODS:SLS I participants received daily oral CYC or matching placebo for 1 year, whereas SLS II participants received daily MMF for 2 years or daily oral CYC for 1 year followed by placebo for second year. We assessed the impact of MMF and CYC on the MRSS in SLS II over a 24-month period. We also compared the change in MRSS in patients with diffuse cutaneous systemic sclerosis (dcSSc) assigned to CYC and MMF in SLS II and SLS I versus placebo in SLS I over a 24-month period using a linear mixed model. RESULTS:In SLS II, the baseline mean ± SD MRSS was 14.0 ± 10.6 units for CYC and 15.3 ± 10.4 units for MMF; 58.5% were classified as dcSSc. CYC and MMF were associated with statistically significant improvements in MRSS from baseline over the period of 24 months in dcSSc (P < 0.05 at each time point), but there were no differences between the 2 groups. In the dcSSc subgroup, the change in MRSS from baseline to all 6-month visits was similar in SLS II groups (MMF, CYC, pooled cohort [MMF + CYC]) and in the SLS I CYC group and showed statistically significant improvements compared to SLS I placebo at 12, 18, and 24 months (P < 0.05). CONCLUSION:In SLS II, MMF and CYC treatment resulted in improvements in MRSS in patients with dcSSc over 24 months. In addition, MMF and CYC treatment resulted in statistically significant improvements in MRSS in patients with dcSSc when compared with the SLS I placebo group.

SUBMITTER: Namas R

PROVIDER: S-EPMC5700860 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials.

Namas Rajaie R Tashkin Donald P DP Furst Daniel E DE Wilhalme Holly H Tseng Chi-Hong CH Roth Michael D MD Kafaja Suzanne S Volkmann Elizabeth E Clements Philip J PJ Khanna Dinesh D

Arthritis care & research 20180209 3

<h4>Objective</h4>To assess the efficacy of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on modified Rodnan skin score (MRSS) in participants enrolled in the Scleroderma Lung Study (SLS) I and II.<h4>Methods</h4>SLS I participants received daily oral CYC or matching placebo for 1 year, whereas SLS II participants received daily MMF for 2 years or daily oral CYC for 1 year followed by placebo for second year. We assessed the impact of MMF and CYC on the MRSS in SLS II over a 24-month pe ...[more]

PMID: 28544580

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Project description:12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide.This randomised, double-blind, parallel group trial enrolled patients from 14 US medical centres with scleroderma-related interstitial lung disease meeting defined dyspnoea, pulmonary function, and high-resolution CT (HRCT) criteria. The data coordinating centre at the University of California, Los Angeles (UCLA, CA, USA), randomly assigned patients using a double-blind, double-dummy, centre-blocked design to receive either mycophenolate mofetil (target dose 1500 mg twice daily) for 24 months or oral cyclophosphamide (target dose 2·0 mg/kg per day) for 12 months followed by placebo for 12 months. Drugs were given in matching 250 mg gel capsules. The primary endpoint, change in forced vital capacity as a percentage of the predicted normal value (FVC %) over the course of 24 months, was assessed in a modified intention-to-treat analysis using an inferential joint model combining a mixed-effects model for longitudinal outcomes and a survival model to handle non-ignorable missing data. The study was registered with ClinicalTrials.gov, number NCT00883129.Between Sept 28, 2009, and Jan 14, 2013, 142 patients were randomly assigned to either mycophenolate mofetil (n=69) or cyclophosphamide (n=73). 126 patients (mycophenolate mofetil [n=63] and cyclophosphamide [n=63]) with acceptable baseline HRCT studies and at least one outcome measure were included in the primary analysis. The adjusted % predicted FVC improved from baseline to 24 months by 2·19 in the mycophenolate mofetil group (95% CI 0·53-3·84) and 2·88 in the cyclophosphamide group (1·19-4·58). The course of the % FVC did not differ significantly between the two treatment groups based on the prespecified primary analysis using a joint model (p=0·24), indicating that the trial was negative for the primary endpoint. However, in a post-hoc analysis of the primary endpoint, the within-treatment change from baseline to 24 months derived from the joint model showed that the % FVC improved significantly in both the mycophenolate mofetil and cyclophosphamide groups. 16 (11%) patients died (five [7%] mycophenolate mofetil and 11 [15%] cyclophosphamide), with most due to progressive interstitial lung disease. Leucopenia (30 patients vs four patients) and thrombocytopenia (four vs zero) occurred more often in patients given cyclophosphamide than mycophenolate mofetil. Fewer patients on mycophenolate mofetil than on cyclophosphamide prematurely withdrew from study drug (20 vs 32) or met prespecified criteria for treatment failure (zero vs two). The time to stopping treatment was shorter in the cyclophosphamide group (p=0·019).Treatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for 2 years or cyclophosphamide for 1 year both resulted in significant improvements in prespecified measures of lung function over the 2 year course of the study. Although mycophenolate mofetil was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than cyclophosphamide was not confirmed. These findings support the potential clinical effectiveness of both cyclophosphamide and mycophenolate mofetil for progressive scleroderma-related interstitial lung disease, and the present preference for mycophenolate mofetil because of its better tolerability and toxicity profile.National Heart, Lung and Blood Institute, National Institutes of Health; with drug supply provided by Hoffmann-La Roche and Genentech.

Project description:Background: Although there are multiple ways to manage immunoglobulin G4-related disease (IgG4-RD), including treatment with glucocorticoids, "steroid-sparing" immunosuppressive drugs, or biologic agents, few clinical trials on IgG4-RD have been conducted. This study aimed to compare the efficacy and safety of glucocorticoids (GCs) combined with cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in IgG4-RD patients. This cohort study was registered at ClinicalTrials.gov (ID: NCT01670695). Methods: This retrospective study included 155 IgG4-RD patients who received GCs with CYC or MMF at the Department of Rheumatology at Peking Union Medical College Hospital between January 2012 and July 2018. Propensity score matching (PSM) was conducted to match two groups of patients based on their baseline clinical characteristics. Treatment response, relapse rate, and drug safety were analyzed. The treatment response was evaluated based on complete response (CR), partial response (PR), and no change (NC), and the cumulative relapse rate and adverse events in each treatment group were compared using Kaplan-Meier curves and log-rank test, respectively. Results: Of the 155 IgG4-RD patients, 90 were treated with GCs plus CYC (group I) and 65 with GCs plus MMF (group II). After propensity score-matched (PSM) analysis, 108 patients were selected (54 in each group), 49 of whom had "definite" IgG4-RD, 8 "probable" IgG4-RD, and 51 "possible" IgG4-RD. At the last follow-up, the total response in groups I and II was 98.15 and 96.3%, respectively, and within 12 months, the cumulative relapse rate in group II was significantly higher than that in group I (14.8 vs. 3.7%, P = 0.046). Recurrence occurred at the paranasal sinus, lacrimal glands, skin, lung, pancreas, and bile ducts, and the relapsed patients achieved remission after switching immunosuppressants or/and increasing the GC dose. Conclusions: In IgG4-RD patients with internal organ involvement, GCs plus CYC or MMF are both effective with similar effects in disease response, while GCs plus CYC reduced the relapse rate better than GCs plus MMF.

Project description:BACKGROUND:The management of proliferative lupus nephritis (LN) comprises timely and coordinated immunosuppressive therapy. This study aimed to evaluate and compare the effectiveness and safety profile of low dose mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in induction therapy of LN in Nepalese population. METHODS:We conducted a prospective, open-label, randomized trial over a period of one and half years. Forty-nine patients with class III to V lupus nephritis were enrolled, out of which 42 patients (21 in each group) could complete the study. CYC was given intravenously as a monthly pulse and MMF was administered orally in the tablet form in the maximum daily dose of 1.5 g in two divided doses. RESULTS:The mean age of the patients was 25.43?±?10.17 years with female to male ratio of 7.3:1. Mean baseline serum creatinine was 1.58?±?1.38 mg/dL and eGFR was 62.38?±?26.76 ml/min/1.73m2. Mean 24-h urinary protein was 4.35?±?3.71 g per 1.73 m2 body surface area. At 6 months, serum creatinine (mg/dL) decreased from 1.73 to 0.96 in CYC and from 1.24 to 0.91 in the MMF group with improvement in eGFR (ml/min/1.73 m2) from 60.33 to 88.52 in CYC and from 64.42 to 89.09 in MMF group. Twenty-four-hour urinary protein (gm/1.73m2) reduced from 4.47 to 0.94 in CYC and from 4.5 to 0.62 in the MMF group. Primary end point was achieved in higher percentage of patients with MMF than CYC (28.6% vs. 19%) while equal proportion of patients (67% in each group) achieved secondary end point in both groups. Number of non-responders was higher in CYC group than in the MMF group (14.3% vs. 4.8%). There was no difference in the rate of achievement of secondary end point in both CYC and MMF groups (3.16 vs. 3.05 months). The occurrence of adverse events was higher in the CYC than in MMF group (56 vs. 15 events). CONCLUSION:Present study has concluded that MMF, used in relatively lower dose, is equally effective in inducing remission with reduction of proteinuria and improvement of kidney function with lesser adverse events than CYC in the induction therapy of proliferative lupus nephritis. TRIAL REGISTRATION:Retrospectively registered to ClinicalTrials.gov PRS. NCT03200002 (Registered date: June 28, 2017).

Dataset Information

Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials.

Publications

Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials.

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