BACKGROUND: Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day. Thus, patients who weigh ≥67 kg receive 3 g/day and a variable dose/kg of MMF.
OBJECTIVE: We investigated the impact of MMF dose/kg on clinical outcomes following haploidentical PBSCT with PTCy-based GVHD prophylaxis.
METHODS: All consecutive adult patients with hematologic malignancies receiving haploidentical T cell replete peripheral blood stem cell transplant (PBSCT) with PTCy/MMF and either tacrolimus or sirolimus at the Moffitt Cancer Center or City of Hope between April 2014-August 2020 were included. For analyses, MMF dose relative to patient actual body weight (mg/kg/day), was stratified into categories of low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day).
RESULTS: Three hundred eighty-six patients were included. Of these, 54 patients received low dose, 73 low intermediate, 137 high intermediate and 122 high dose MMF by relative weight exposure. In multivariate analysis, low MMF dose exposure was associated with reduced rates of relapse in comparison to the high dose group (HR=0.45, 95% CI: 0.21 to 0.94, p=0.03). This led to superior PFS among patients with low compared to high MMF dose exposure (HR=0.58, 95% CI: 0.34 to 0.99, p=0.045). MMF relative dose exposure was not associated with engraftment, GVHD, non-relapse mortality, or OS.
CONCLUSIONS: In this study of patients receiving haploidentical PBSCT with PTCy based GVHD prophylaxis, low MMF dose/kg was associated with improved rates of relapse and PFS. Future prospective studies should investigate optimal dosing strategies of MMF when given with the PTCy regimen.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

BACKGROUND: Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis that has been effectively treated with azathioprine and mycophenolate mofetil (MMF) in uncontrolled studies. We conducted a prospective randomized controlled trial to compare the efficacy and safety of azathioprine and MMF in CAD treatment, aiming to address existing evidence gaps.
METHODS: Consecutive CAD patients were randomized into two groups: azathioprine (Group A) or MMF (Group B) for 12 weeks. Primary outcomes included Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and Week 12. Secondary outcomes included various clinicodemographic factors predictive of treatment response, defined at least a 75% reduction in EASI score (EASI75) by Week 12.
RESULTS: The median (IQR) percentage reduction in EASI at 12 weeks was higher in Group B than in Group A [78.3% (75.0-83.30%) vs. 68.3% (31.2-80.10%), P = 0.034]. Baseline DLQI scores indicated a moderate impact on quality of life, with significant reductions by Week 12 in both groups and no intergroup differences at baseline (P = 0.291) or Week 12 (P = 0.599). Overall, 23 patients were classified as non-responders, with more extended illness duration (P = 0.026) and outdoor occupations (P = 0.042) associated with poorer responses. Adverse effects were consistent with known profiles, with one patient discontinuing azathioprine due to hypersensitivity.
CONCLUSIONS: Our study highlights the efficacy and safety of azathioprine and MMF in CAD treatment, with MMF showing superior outcomes. However, further research is warranted to explore emerging therapies and prognostic factors in CAD management.

Hepatoxicity associated with recombinant adeno-associated virus gene therapy is being increasingly encountered by hepatologists in tertiary and quaternary referral units due to the recent increase of these therapies for neuromuscular and haematological disorders. The challenges in managing the condition stem from a lack of good-quality evidence on the appropriate protocols for immunosuppressants due to lack of representative animal models. There is a need for protocols for diagnosing and treating hepatotoxicity and this possible with further research to understand the problem and its management. The review also highlights the importance of a multidisciplinary team in managing hepatotoxicity and recommends further research to better identify at-risk individuals, define the extent of the problem and assess the long-term effects of liver injury and immunosuppressants.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder. With the method of indirect immunofluorescence assay (IIF), more anti-NMDAR encephalitis patients have been discovered when its first onset. But it was rare that anti-NMDAR encephalitis overlapped with multiple sclerosis (MS) documented in literatures. Here, we present a case who initially developed anti-NMDAR encephalitis and MS. Furthermore, we concluded the characteristics of patients who were diagnosed as anti-NMDAR encephalitis overlapping with MS. Additionally, due to the relapsing process, mycophenolate mofetil and sequentially fingolimod for the treatment were taken, which subsequently led to the development of a lymphoproliferative disease in his brain and other organs. This case illustrates the complex role of immunosuppressive agents.

UNASSIGNED: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability.
UNASSIGNED: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention.
UNASSIGNED: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

This mini-review explores glucocorticoids, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ) in IgA nephropathy (IgAN). It discusses conflicting findings from pivotal trials like TESTING and STOP-IgAN regarding glucocorticoid efficacy, emphasizing reduced-dose protocols as potentially safer options. MMF\'s effectiveness varies among populations, demonstrating promise in Chinese cohorts but yielding inconclusive results elsewhere. HCQ shows potential in reducing proteinuria, with ongoing trials investigating its long-term benefits.

UNASSIGNED: There is no consensus on the timing of immunotherapeutic strategies for the first-episode anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) associated disorders (MOGAD) presenting with isolated optic neuritis (ON).
UNASSIGNED: To investigate the optimal timing of intravenous methylprednisolone therapy (IVMP) and necessity of immunosuppressive therapy for the first-episode isolated MOG-IgG associated ON (iMOG-ON).
UNASSIGNED: Adult patients with the first-episode iMOG-ON were enrolled. Primary outcomes were best-corrected visual acuity (BCVA) at last follow-up (i.e. final BCVA) and relapse, and their predictors were assessed by multivariate analysis.
UNASSIGNED: 62 patients were included. Logistic regression analysis revealed BCVA at the time of IVMP (odds ratio: 0.463 (95 % confidence interval (CI) 0.310-0.714) was a factor predictive of regaining a final BCVA of 0.0 logMAR vision, and its Youden optimal criterion was <0.175 logMAR by plotting the receiver operating characteristic curve. The time-dependent cox proportional hazards model exhibited MMF therapy was not associated with a high likelihood of relapse-free survival (HR = 1.099, 95 % CI 0.892-1.354, P = 0.376) after adjusting for age of onset, gender, and baseline MOG serum titers. Similar analysis exhibited evidently negative association between high MOG-IgG serum titers at baseline and relapse-free survival after adjusting for age of onset, gender, and MMF therapy (HR = 0.339, 95 % CI 0.155-0.741, P = 0.007).
UNASSIGNED: During the first episode of iMOG-ON, the optimal timing of IVMP may be a short timeframe before visual acuity decreasing to 0.175 logMAR, and MMF therapy may not be recommended for patients with low MOG-IgG serum titers. Further long-term follow-up studies are required to validate these findings.

Juvenile dermatomyositis (JDM) patients who test positive for the antimelanoma differentiation-associated gene 5 (MDA5) antibody have a poor prognosis because of rapidly progressing interstitial lung disease (ILD). However, agreement on the best treatment for this condition remains elusive. We encountered a 13-year-old girl with anti-MDA5 antibody-positive JDM who presented with arthritis and was already showing signs of ILD when she was admitted to the hospital. While cyclophosphamide (CY) is commonly used, it can cause gonadal disorders and other complications when administered to adolescent females. Consequently, we chose multitarget therapy, which includes tacrolimus and mycophenolate mofetil. Her ILD and skin symptoms gradually improved, and she was able to maintain remission and avoid CY administration for three years. We conducted a thorough literature review to determine the efficacy and safety of multitarget therapy for anti-MDA5 antibody-positive DM and JDM. Multitarget therapy shows promise as a potentially effective and relatively safe treatment. The ability to avoid CY, which is especially important for adolescent patients concerned about fertility preservation, highlights a significant benefit of this multitarget therapy for anti-MDA5 antibody-positive DM and JDM patients.

BACKGROUND: The optimal treatment of fibrosing hypersensitivity pneumonitis (fHP) is not well understood. The aim of the study was to obtain information about the usefulness of mycophenolate mofetil (MMF) in its treatment.
METHODS: Quasi-experimental analysis of patients diagnosed with fHP and treated with MMF for one year, in a single centre. From the start of treatment, data collection was prospective.
RESULTS: 73 were included and 58 completed the study. FVC% and DLCO% decreased until starting MMF (year -1 to year 0). After completion of treatment (year 1), FVC% stabilised (p=0.336) and DLCO% improved significantly (p=0.004) compared to year 0. Dyspnoea, number of patients without corticosteroids and mean corticosteroid dose also improved significantly (p<0.001 in all cases). Being male and having a history of tuberculosis were predictors of poor drug response [AUC = 0.89 (95% CI: 0.80-0.98)]. 45 adverse effects were observed in 34 patients (46.6%). In 4 cases (5.5%), the adverse effect was severe and required discontinuation of treatment.
CONCLUSIONS: In patients with fHP, MMF improves lung function and dyspnoea and reduces both the number of patients requiring oral corticosteroids and their mean dose in those who completed 1 year of treatment. The model constructed predicts which patients will respond poorly to treatment, with good discriminative ability and only a small percentage of patients will not tolerate treatment. Further prospective, randomised clinical trials are needed to define the role of this treatment in fHP.