Efficacy Of Mycophenolate Mofetil Research Articles

Efficacy and safety of oral cyclophosphamide versus mycophenolate mofetil in childhood nephrotic syndrome: an open-label comparative study

IntroductionThere is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders).MethodsThis open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2–2.5 mg/kg once daily for a period of 8–12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800–1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria.ResultsIn the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25–11) compared to 7 months (IQR 3.5–12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468).ConclusionsThe efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure.Registration of the study with Clinical Trials Registry of India(http://ctri.nic.in;CTRI/2021/06/034421) (Dt: 28/06/2021).

Early combination with mycophenolate mofetil for immune-related hepatitis in patients with solid tumors treated with immune checkpoint inhibitors.

12133 Background: Hepatitis, as an immune-related adverse event (irAE), occurs in 2%-10% of patients treated with immune checkpoint inhibitors (ICIs). Although guidelines recommend the use of mycophenolate mofetil (MMF) for steroid-refractory and steroid-resistant ir-hepatitis, there has been no evidence on the efficacy of MMF. Methods: We retrospectively reviewed consecutive patients with solid tumors who developed grade 2 or higher ir-hepatitis requiring systemic steroids after ICIs (nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab and ipilimumab) between January 2015 and August 2023. The changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin level, according to the CTCAE version 5.0, were used to assess ir-hepatitis. ALT improvement was calculated as the ratio of the change in ALT values from onset to day 7, normalized by the ALT values at onset. Results: Among 4405 patients treated with ICI during the study period, 130 patients (3%) developed grade 2 or higher ir-hepatitis requiring systemic steroids. The median age was 62 (range: 19-85) years-old, and 122 patients (94%) had an ECOG performance status (PS) 0/1. These patients included 67 (52%) with melanoma, 35 (27%) with lung cancer, 7 (5%) with esophageal cancer, and 21 (16%) with other cancers. Among 123 evaluable patients, 46 patients (46/123, 37%) received MMF including 20 patients experiencing steroid-refractory and 26 steroid-resistant. The median duration from the start of systemic steroids to MMF was 11 days (range: 0-113 days). Improvement of hepatitis to grade 1 with MMF was observed in 40 patients (40/46, 87%) with a median time of 18 (range: 3-176) days. Of the patients evaluated for the impact of the timing of MMF on the improvement of ir-hepatitis (n=38), ALT improvement at day 7 after ir-hepatitis onset in patients who initiated MMF within 3 days of ir-hepatitis onset (early combination group, n=8) was significantly higher compared with the patients who initiated MMF after 3 days of ir-hepatitis onset (late combination group, n=30) (72.3% vs. 41.7%, p=0.02). Additionally, among patients evaluable for systemic steroid dosage (n=45), the total systemic steroid dosage in patients in the early combination group (n=8) was significantly less than in the late combination group (n=37) (median: 2120mg vs 4005 mg, p=0.02). Conclusions: MMF was effective for both steroid-refractory and steroid -resistant ir-hepatitis. Early combination with MMF in addition to systemic steroids can lead to a more rapid improvement of ir-hepatitis compared to late combination with MMF consequently reducing the total systemic steroid dosage. [Table: see text]

Comparison of efficacy of continuous mycophenolate mofetil with sequential cyclophosphamide and tacrolimus as maintenance therapy for lupus nephritis.

To evaluate the renal response to mycophenolate mofetil (MMF) as maintenance therapy for lupus nephritis (LN) in Japanese patients, we compared the efficacy of MMF and the sequential use of monthly intravenous cyclophosphamide (IVCY) followed by tacrolimus (TAC). We examined 14 patients with LN who were treated with continuous MMF as induction and maintenance therapies (MMF group) and 10 patients with LN who received monthly IVCY as induction therapy followed by maintenance therapy with TAC (IVCY-TAC group). We assessed the therapeutic effects of each treatment regimen on renal manifestations and serological findings over a 36-month period after treatment initiation. Mean urine protein-to-creatinine ratios in the MMF and IVCY-TAC groups significantly decreased from 2.75 to 0.11g/gCr and from 3.26 to 0.22g/gCr, respectively. Significant improvements in serum immunological variables (serum complement C3 or C4 levels and the anti-double-stranded DNA antibody titer) and reductions in the SLE disease activity index and daily prednisolone dosages were observed in both groups during induction therapy and were maintained during maintenance therapy. Efficacy was similar between the MMF and IVCY-TAC groups. MMF has potential as an effective treatment for renal manifestations in Japanese patients throughout induction and maintenance therapies for LN, as an alternative to conventional IVCY-TAC therapy, and as a glucocorticoid-sparing agent.

Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population.

Integrative analysis of purine metabolites and gut microbiota in patients with neuromyelitis optica spectrum disorders after mycophenolate mofetil treatment

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a recurring inflammatory demyelinating disease that is commonly observed in Asian countries like China. Prior investigations have shown that mycophenolate mofetil (MMF) with better biocompatibility compared to azathioprine (AZA), and can prevent relapses of NMOSD, but the efficacy was controversially reported in different NMOSD cases. We aimed to explore the factors that weaken efficacy of MMF in NMOSD.MethodsA total of 34 NMOSD patients treated with MMF were prospectively enrolled and grouped according to the therapeutic efficacy as effective group (EG, n = 23) versus less-effective group (LEG, n = 11). The purine metabolites were profiled in serum samples and gut microbiota was analyzed using 16S rRNA sequencing with stool samples from the same patients.ResultsPurine salvage pathway (PSP) metabolites (inosine, hypoxanthine, xanthine, guanine and uric acid) in the serum of NMOSD patients were elevated in the LEG compared to EG (p < 0.05). Additionally, the richness and microbial diversity of gut microbiota was found to be similar between EG and LEG patients. However, LEG patients had increased presence of Clostridium and Synergistes but decreased abundance of the Coprococcus genus.ConclusionsThe PSP metabolites and composition of the gut microbiota were changed between patients with or without optimal clinical response after MMF treatment. This may help us to understand the pharmacodynamics of MMF in NMOSD.

Mycophenolate mofetil in giant cell arteritis.

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the large arteries. Abnormal lymphocyte function has been noted as a pathogenic factor in GCA. Mycophenolate mofetil (MMF) inhibits inosine monophosphate dehydrogenase and is therefore a highly lymphocyte-specific immunosuppressive therapy. We aimed to assess the efficacy of MMF for inducing remission in GCA. Seven patients (5 female, 2 male) with GCA under therapy with MMF and who were treated at the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School between 2010 and 2023 were retrospectively included in the study. All patients underwent duplex sonography, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and/or biopsy to confirm the diagnosis. The primary endpoints were the number of recurrences, CRP levels at 3-6 and 6-12 months, and the period of remission. All patients in this case series showed inflammatory activity of the arterial vessels in at least one of the imaging modalities: duplex sonography (n = 5), 18F-FDG PET (n = 5), MRI (n = 6), and/or biopsy (n = 5). CRP levels of all patients decreased at the measurement time points 3-6 months, and 6-9 months after initiation of therapy with MMF compared with CRP levels before MMF therapy. All patients with GCA in this case series achieved disease remission. The results of the present case series indicate that MMF is an effective therapy in controlling disease activity in GCA, which should be investigated in future randomized controlled trials.

#5827 MYCOPHENOLATE MOFETIL AS IMMUNOSUPPRESSIVE THERAPY IN IGA NEPHROPATHY

Abstract Background and Aims IgA Nephropathy is the commonest cause of primary Glomerulonephritis in developed countries. It is characterised by IgA-dominant deposits in the mesangium on renal biopsy. Classically presenting with asymptomatic non-visible haematuria or episodic visible haematuria 24-48 hours after an upper respiratory tract infection, raised BP and Proteinuria. End-stage renal disease (ESRD) can occur in up to 20-50% of patients. Treatment with ACEI/ARB has strong evidence in managing IgA. If there is evidence of progression, steroids and immunosuppression are recommended. Mycophenolate Mofetil's effectiveness in IgA nephropathy is controversial. KGIGO guidelines authors suggest not to use it. In this work, we reviewed immunosuppression with mycophenolate Mofetil (MMF) retrospectively in IgA nephropathy patients managed at Sussex Kidney unit – Brighton -UK. Method We retrospectively reviewed 25 patients who had a diagnosis of IgA nephropathy and were treated with mycophenolate mofetil as immunosuppression for IgA nephropathy under the care of the Sussex Renal Unit at University Hospitals Sussex. Patients reviewed, had been diagnosed between 2011-2020. Data collected from our department's electronic system, including laboratory results, histopathology reports, clinic letters and medications. Data were collected until January 2023 for patients who had renal survival. For patients who started on renal replacement therapy (RRT), data were collected until the start of RRT. The work aimed at looking at MMF efficacy in IgA nephropathy. The primary measures were renal survival without the need for RRT and proteinuria reduction to &amp;gt; 50% of the baseline at diagnosis. Results We reviewed 25 patients, 13 male and 12 female. Twenty-four patients (96%) were of white Caucasian ethnicity while one patient (4%) was Asian. The mean age was 42.4± 16 years. All the patients were diagnosed with both clinical pictures and renal biopsies. Oxford classification score showed M1 (21) patients, E (5 patients), S (19 patients), T (1 = 10 patients, 2 = 4 patients), and C (1 = 15 patients, 2 = 4 patients). On presentation, 5 patients presented with a sore throat, 8 with skin rash and 7 with macroscopic haematuria. Seventeen patients (60%) presented with AKI. Eleven patients (44%) had nephrotic range proteinuria on presentation. The average duration of the disease was 6.1 years at the time of assessment. MMF was used in the 25 patients, five of them had prednisolone and cyclophosphamide for 3 months followed by MMF maintenance. Twenty patients were treated with MMF alone or in combination with steroids (17 patients) from the start. The average duration of treatment was 2 years, and the average dose was 1 gm twice daily. Five patients (20%) progressed to ESRD and three of them had renal transplantation while twenty patients (80%) maintained renal survival. For the 80% who maintained renal survival the mean eGFR at diagnosis was 45.6± 34.1 and at the time of assessment was 56.1±26.6. Of the 17 patients presented with AKI, five patients (29.4%) recovered to normal renal function, five patients had ESRD (29.4%) and four had improvements of eGFR while three patients showed a decrease of eGFR (Mean 45.6± 1.1 ml/min) to eGFR (Mean 32± 8.2 ml/min). In total, 70.6% of AKI patients recovered either to normal or to CKD level and 80% of the total patients had renal survival without RRT during the time of review. Twenty patients (80%) achieved more than 50% reduction of proteinuria, with five patients (20%) having proteinuria less than 0.3 g/24 hours and 9 (36%) patients less than 0.5 g/24 hours. Comparison between the proteinuria at diagnosis and at the time of assessment was significant (P&amp;lt;0.001). Conclusion Mycophenolate mofetil was effective in maintaining renal survival and improving proteinuria in IgA nephropathy patients who were indicated for immunosuppression based on histopathology and risk of progression. It was well tolerated by patients. A randomised controlled trial is needed to compare the MMF effect in comparison with currently available therapies.

Interventions for preventing and treating kidney disease in IgA vasculitis.

Interventions for preventing and treating kidney disease in IgA vasculitis.

Mycophenolate mofetil: An alternative disease-modifying agent for MOG-IgG-associated disorders in childhood: A single-center bidirectional cohort study

ObjectiveTo evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of childhood MOG-IgG-associated disorder (MOGAD). MethodsThirty patients diagnosed with relapsing MOGAD and treated with MMF for >1 year from a childhood MOGAD ambispective cohort were included in the study. The clinical characteristics, therapeutic regimen, side effects, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores of these patients were evaluated. ResultsThe median age of disease onset was 7.05 (2.50–12.75) years. The male to female ratio was 1:1.31. All patients used MMF as first-line maintenance treatment. The median time to add MMF from disease onset was 1.08 (0.25−5.00) year. The median number of attacks before MMF initiation was 2 (2 − 8). The median duration of MMF therapy was 2.13 (1.00−3.58) years. Twenty (66.67%) patients did not experience further attacks during MMF therapy. The Kaplan–Meier curves showed a 3-year relapse-free rate of 59.8% (95% CI, 36.62−76.88%). ARR decreased during MMF therapy (0 (0 − 1.72) vs. 1.25 (0.60−4.00); P < 0.05). EDSS stabilized during MMF therapy (1.0 (0 − 2.0) vs. 0 (0 − 2.0); P = 0.206). None of the patients stopped the use of MMF due to intolerable side effects. Onset age, sex, phenotype of the first attack, ARR before MMF, MOG-IgG titers, and combined long-term prednisone (prednisone <10 mg daily for patients >40 kg or <5 mg daily for patients ≤40 kg longer than 6 months) did not predict recurrence during MMF therapy in univariate analysis. ConclusionsMMF was effective and safe for treating childhood MOGAD. No clinical feature that could predict efficacy of MMF was found in pediatric patients with MOGAD.

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation.

Mycophenolate mofetil (MMF) is the gold-standard immunosuppressive agent in heart transplantation (HT), but dose-dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria β-d-glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high-dose, HD] versus 1 g q12 [low-dose, LD] and explore the association between neutropenia and GUS. We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post-HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing. A total of 168 patients (120 MMF-HD, 48 MMF-LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 [64-143] days. Freedom from neutropenia was lower in MMF-HD compared with MMF-LD (57% vs. 73%, p=0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10-96] days, while high-grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9-89] days. Freedom from ACR was similar between groups. MMF-LD was associated with more high-grade ACR (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09-11.08, p=0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29-1.00, p=0.05) between 1 and 6 months. GUS-producing bacteria were more abundant in neutropenic patients. MMF-LD was associated with higher rates of early high-grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post-HT.

Treatment outcomes of Pediatric Lupus Nephritis Class III and IV in National Children’s Hospital

Treatment of lupus nephritis (LN) remains challenging. A prospective observational study on the children with newly diagnosed LN class III and IV from 9/2019 to 9/2021 intended to examine the efficacy of MMF with corticosteroids as induction therapy for pediatric lupus nephritis class III and IV. All patients received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy in combination with Mycophenolate mofetil (MMF) 1200mg/m2/day (max 2g/day). Those with urine protein-creatinine ratio (uPCR) &gt; 200mg/mmol and normal renal function after 1-month treatment received MMF and low dose Calcineurin Inhibitors (CNI). There were 57 children who were 75.4% females, 42.1% of children in class III, and 57.9% in class IV. The mean age was 10.88. 82.5% of patients r eceived Corticosteroid and MMF, and 10 children were treated with Corticosteroid, MMF, and CNI. Early responses at week 12 were achieved by 71.9%. The overall response was seen in 93.3% of patients after 6 months of therapy ( 42.2% complete response and 51.1% partial response). 2 patients (3.5%) had infections. MMF is effective in the treatment of children with proliferative lupus nephritis in induction therapy.

Induction and maintenance of remission with mycophenolate mofetil in ANCA-associated vasculitis: a systematic review and meta-analysis.

Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P&gt;0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2=74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

CTNI-15. PHASE 0/I TRIAL OF MYCOPHENOLATE MOFETIL COMBINED WITH RADIATION TO OVERCOME GLIOBLASTOMA TREATMENT RESISTANCE BY TARGETING DE-NOVO PURINE METABOLISM: INTERIM REPORT

Abstract BACKGROUND De novo purine synthesis promotes glioblastoma growth and stemness, invasiveness, and resistance to chemoradiation. Mycophenolate mofetil (MMF) is an FDA-approved inhibitor of de novo purine synthesis that sensitizes glioblastoma to radiation and chemotherapy in mice. This Phase 0/I trial of MMF with Radiotherapy in Recurrent Glioblastoma (NCT04477200) aims to determine the maximum-tolerated dose of MMF that can be combined with radiation,and the extent to which the active metabolite of MMF accumulates in brain tumors and inhibits de novo purine synthesis. METHODS Key eligibility criteria are age ≥18, KPS score ≥60%, and recurrent glioblastoma or gliosarcoma with clinical indication for re-irradiation (phase I) or re-resection/biopsy (phase 0). Patients with tumors involving ≥3 lobes or leptomeningeal space or bevacizumab use within 8 weeks are excluded. MMF 500-2000mg PO BID is given one week pre-operatively in Phase 0 (N=8), and up to 2000mg PO BID (starting 1000mg) on TITE-CRM dose escalation on Phase 1 cohort (N=30). RESULTS Since 7/2020, three Phase 0 and six Phase I subjects have been enrolled. On the phase I cohort, 1500mg BID dose has been reached. Studyrelated toxicities have been limited to mainly grade 1-2 nausea and fatigue. No notable study related hematotoxicity have been noted. Additionally, mass spectrometry-based correlative measurements of the activity of de novo GTP synthesis are ongoing. CONCLUSION MMF has been well tolerated up to 1500mg BID combined with radiotherapy in recurrent glioblastoma patients in this interim analysis. An additional upfront glioblastoma cohort with MMF with standard of care will activate in 2021. These studies will determine the maximum tolerated dose of MMF in combination with radiation and chemotherapy and provide a preliminary efficacy estimate at that dose. Encouraging results would support a randomized clinical trial to determine efficacy of MMF combined with chemoradiation in glioblastoma, and to define potential biomarkers for effectiveness.

A retrospective evaluation of the steroid sparing effects of oral mycophenolate mofetil (MMF) as an adjunct immunosuppressant for the treatment of canine pemphigus foliaceus.

Oral mycophenolate mofetil (MMF) currently is considered a low-risk steroid-sparing therapeutic option for the management of canine pemphigus foliaceus (PF). This retrospective study evaluates the therapeutic outcomes of dogs with PF treated with the combination of oral MMF and glucocorticoid (GC). Clinical outcomes and adverse side effects are reported. Eleven dogs diagnosed with PF. Retrospective review of medical records from dogs presented with PF to the dermatology service of a veterinary teaching hospital between 2015 and 2020. Eleven dogs were identified which had received concurrent GCs and MMF. The MMF dose range was 19.8-45 mg/kg/day. Only two dogs (two of 11) treated with a mean MMF dosage of 39 mg/kg/day along with oral prednisone or dexamethasone achieved complete remission (CR). Partial remission (PR) was achieved in four of 11 dogs who received either prednisone, prednisolone or dexamethasone along with MMF (mean dosage 26 mg/kg/day). Four dogs (four of 11) showed poor response to MMF given at 28.5 mg/kg/day along with prednisone or dexamethasone. In one dog (one of 11) MMF was discontinued due to severe GI upset; transient vomiting and diarrhea was observed in four of 11 dogs. The median duration of MMF therapy in conjunction with GC for all groups was 70.5 days. Tapering of oral GCs while continuing MMF administration at the same dosage and frequency led to recurrence of lesions in all PF patients. Oral MMF combined with GC achieved CR in two of 11 PF dogs included in this study. Further research of MMF efficacy in PF may need to be performed.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma.

Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Mycophenolate mofetil versus methotrexate for vulvar lichen planus: A 10-year retrospective cohort study demonstrates comparable efficacy and tolerability

Mycophenolate mofetil versus methotrexate for vulvar lichen planus: A 10-year retrospective cohort study demonstrates comparable efficacy and tolerability

Safety and efficacy of mycophenolate mofetil in myelin oligodendrocyte glycoprotein‐immunoglobulin G‐associated disorder among adults: A meta‐analysis

AbstractObjectiveMyelin oligodendrocyte glycoprotein immunoglobulin G‐associated disorder (MOGAD) is an autoimmune demyelinating disorder of the central nervous system having distinct clinical phenotypes and epidemiological distribution than multiple sclerosis and neuromyelitis optica spectrum disorder. Mycophenolate mofetil has shown good safety and efficacy in multiple sclerosis and neuromyelitis optica spectrum disorder patients, but the published case series and observational studies of MOGAD showed contrasting results. Thus, we felt the need to carry out a meta‐analysis.MethodsWe searched PubMed, Embase, Cochrane Library, Google Scholar and additional sources for suitable studies. Meta‐analysis through representative forest plot was carried out for the proportion of relapse‐free patients, change in annualized relapse ratio and Expanded Disability Status Scale before and after treatment, and reduction of relapse risk.ResultsA total of nine studies were included in our meta‐analysis. Mycophenolate mofetil treatment showed approximately half the proportion (49%; 95% CI 0.26–0.73, P &lt; .001) of relapse‐free patients at follow up. It also significantly reduced the mean annualized relapse (mean difference 0.76, 95% CI 0.49–1.03, P &lt; .001) and relapse risk (hazard ratio 1.25, 95% CI −2.48 to −0.01, P &lt; 0.05), but did not show a significant difference in change in Expanded Disability Status Scale score (mean difference 0.34, 95% CI −0.79 to 1.47, P = 0.56). On subgroup analysis, administration of a high dose (&gt;2000 mg/day) showed a greater proportion of relapse‐free patients. Infections, leukopenia, fatigue, alopecia and diarrhea were common side‐effects. A total of 10.32% of patients discontinued treatment, mainly due to treatment failure.ConclusionsThe present meta‐analysis shows mycophenolate mofetil therapy as cost‐effective, well tolerated and effective for the treatment of relapses in MOGAD among adult patients.

Efficacy of mycophenolate mofetil versus cyclophosphamide in systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis.

This study systematically compares the efficacy and adverse events of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD). The EMBASE and PubMed databases were systematically searched to find all relevant studies. Quality assessment, study selection, and data extraction were independently conducted by two reviewers. The mean changes in forced vital capacity (FVC)% and diffusing capacity for carbon monoxide (DLco)% of the patients were selected to be primary outcome measures. Stata software was used for the pooled analysis. Among 284 titles screened from multiple databases, six studies met the inclusion criteria (one randomized controlled trial, three prospective observational studies, and two retrospective observational studies). The summary weighted mean difference (WMD) of FVC change in the MMF group compared with the CYC group was - 1.17 (95% CI: - 2.713, 0.373; P = 0.137), and the summary WMD of DLco change in the MMF group compared with the CYC group was 2.245 (95% CI: 0.258, 4.232; P = 0.027). Studies enrolled showed that adverse events were less common in the MMF group. The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events. Key Points • A systematic review and meta-analysis was conducted to compare the efficacy and adverse events of mycophenolate mofetil and cyclophosphamide in patients with systemic sclerosis-related interstitial lung disease. • The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events.

POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p&lt; 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.

Efficacy of Mycophenolate Mofetil in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Systematic Review and Meta-analysis (5066)

Efficacy of Mycophenolate Mofetil in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Systematic Review and Meta-analysis (5066)