Mycophenolate Mofetil Therapy Research Articles

P.010 Safety and efficacy of inebilizumab in AQP4+ NMOSD participants with history of immunosuppression treatment prior to N-MOmentum study

Background: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.

IgA nephropathy in a child with X-linked agammaglobulinemia: a case report

BackgroundX-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA.Case presentationIn this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria.ConclusionsIn this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.

Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies

IntroductionIdiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM.MethodsPatients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period.ResultsAmong the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed.ConclusionOur data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.

Retrospective Cross-Sectional Study Reviewing the Effectiveness of Mycophenolate Mofetil on Saudi Children With Nephrotic Syndrome.

Background Idiopathic nephrotic syndrome (INS) is the most common form of nephrotic syndrome (NS) in children. It is often associated with minimal change disease (MCD). Corticosteroid therapy is the initial treatment, but many patients experience relapses, leading to steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). To avoid prolonged steroid use, mycophenolate mofetil (MMF) is used as an immunosuppressive alternative. MMF is safe and effective for treating SDNS and FR-SSNS in children, with studies showing reduced relapse rates. The current study aims to evaluate MMF's effectiveness and safety in Saudi children with NS and identify factors that affect its efficacy. Methods A retrospective cross-sectional study was conducted at King Abdullah Specialized Children's Hospital (KASCH) in Riyadh, Saudi Arabia. The study included children aged one to 14 years diagnosed with NS who received MMF therapy. Data were collected from medical records from 2000 to 2020. Ethical considerations were followed, and statistical analysis was performed using IBM SPSS Statistics for Windows, version 25 (released 2017; IBM Corp., Armonk, New York, United States). Baseline characteristics and responsiveness to MMF were examined. Results In our study, 45 participants (25 males, 20 females) with NS were treated with MMF. Most participants were steroid-dependent (84.44%) and had frequent relapses. MMF was effective in 84.4% of cases, with a significant reduction in relapse; the mean number of relapses decreased from 3.5 before MMF to 1.6 after MMF (p-value = 0.00002). Moreover, 40% of the participants were completely free of relapse after the introduction of MMF. The average duration of the MMF therapy was 45 months. Post-MMF side effects were rare but documented. Gastrointestinal symptoms were extremely rare. Elevated liver enzyme levels were reported in 8.88% (four cases) of the participants. Leukopenia, a more common adverse effect, was reported in 26.66% of cases during the MMF therapy. The average daily dose of steroid was reduced from 12.5 mg/day pre MMF to 2 mg/day post MMF with a p-value of 0.00229. Conclusion Our study evaluated the use of MMF in 45 participants with NS. We found that MMF was effective in 84.4% of cases, leading to a significant reduction in the number of relapses. Post-MMF side effects were relatively rare, except for leukopenia that was reported in 26.66%. In addition, the average rate of reduction of steroid exposure before and after MMF was significant. These findings suggest that MMF is a promising treatment option for children with NS and an alternative therapy to long-term steroid use, due to its safety and effectiveness, although close monitoring for potential side effects is essential.

Risk factors associated with multiple organ damage in childhood-onset systemic lupus erythematosus

ObjectivePrevious studies have shown that approximately 39%–65% of patients with childhood-onset systemic lupus erythematosus (cSLE) have damage in at least one organ. Data on risk factors for organ damage in cSLE remain limited, especially in Asian populations. This study was conducted to evaluate the incidence of cSLE and identify the risk factors for accumulated organ damage in patients with cSLE.MethodsThis was a retrospective study. Patients aged <18 years who were diagnosed with cSLE between 2008 and 2020 were enrolled. Information on baseline characteristics, treatment, and disease activity assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was collected from diagnosis until the most recent visits were reviewed from medical records. Disease damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).ResultsA total of 134 patients with a mean age at diagnosis of 11.2 ± 2.9 years were enrolled. The median duration of treatment was 4.7 (interquartile range 2.8–7.1) years. Forty patients (29.9%) had irreversible organ damage (SDI > 1) with an incidence rate of 5.7 events per 100 person-years. The most frequent type of organ damage was ocular (11.1%), followed by musculoskeletal (8.9%) and neurological (7.4%). High disease activity at diagnosis (SLEDAI-2K ≥ 12) (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.32–7.68), infection (OR 3.73, 95% CI 1.60–8.67), and mycophenolate mofetil use (OR 3.62, 95% CI 1.45–9.03) were predictors of organ damage. The median time to disease damage in patients with SLEDAI-2K scores ≥12 at diagnosis was 6.5 years (95% CI 5.77–7.36; P = 0.004).ConclusionPhysicians should be aware of organ damage in patients with cSLE, particularly those with high disease activity at initial presentation, those who are receiving mycophenolate mofetil therapy, and those with an infection.

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.

Symposium 6

The ultimate goal of treatment of systemic lupus erythematosus (SLE) is to prolong survival without compromising the quality of life. The survival rates of SLE have plateaued since the 2000s’ and morbidities related to disease activity and treatment are still problematic. A big unmet need for SLE therapy is to develop strategies that can enhance efficacy, reduce disease flares and drug related complications. Cocktail immunosuppressive therapies for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, risk of infective complications, adoption of a step-up or step-down approach and the choice of agents are still controversial, partly because of the issue of cost-effectiveness. Belimumab is the first biological agent licensed for pediatric and adult patients with renal and non-renal SLE, based on several pivotal randomized controlled trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, BLISS-LN). The continuous use of belimumab enables reduction of disease flares, glucocorticoid doses and organ damage. Anifrolumab, a monoclonal antibody against type I interferon receptors, has shown efficacy for non-renal SLE in the TULIP studies. It is recently licensed for moderate to severe SLE patients who are receiving standard therapies. Although rituximab did not show benefit in renal and non-renal SLE, it is commonly used off-label to treat refractory lupus manifestations. The newer generation anti-CD20 biologic, obinutuzumab, shows promising preliminary results in a phase 2 lupus nephritis (LN) trial. Combination of anti-CD20 and anti-BAFF is being studied in LN but the results are conflicting hitherto. Ianalumab, a monoclonal antibody against BAFF receptor that exhibits dual mechanisms of action (BAFF inhibition and B cell depletion), is being studied in LN. The updated 2023 EULAR recommendations for SLE have included the role of biological agents in the treatment algorithm. Belimumab and anifrolumab may be considered in non-major organ SLE, including skin disease, that is refractory to hydroxychloroquine with or without other immunosuppressive agents. Initial combination therapy of glucocorticoids, mycophenolate mofetil or low dose cyclophosphamide, with belimumab is an option for the treatment of severe LN, and belimumab may be used as long-term maintenance therapy of SLE/LN. In this talk, the evidence and the role of the older and newer biologic and targeted agents in SLE/LN will be reviewed.

Long-Term Efficacy and Relapse in Lupus Nephritis Treated with Mycophenolate Mofetil and Tacrolimus Combination Therapy

Long-Term Efficacy and Relapse in Lupus Nephritis Treated with Mycophenolate Mofetil and Tacrolimus Combination Therapy

Safety and efficacy of immune checkpoint inhibitor cancer therapy in patients with preexisting type 1 diabetes mellitus.

Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.

Uptitrating mycophenolate mofetil therapy in a patient with lupus cerebritis doesn’t increase risk of infection compared to cyclophosphamide

A clinical decision report using: Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112. https://doi.org/10.1681/ASN.2008101028 for a patient with neuropsychiatric lupus.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study.

Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.

Efficacy of rituximab in difficult to treatment patients with polymyositis

Inflammatory myopathies are a heterogeneous group of diseases rarely encountered in clinical practice. They primarily involve the transverse striated muscles, and in some cases there is also extramuscular involvement of the skin, lungs, joints, esophagus, heart. Acute forms of myositis, which are the most common, are associated with viral diseases and usually resolve spontaneously. Chronic forms usually have a subacute onset and unknown etiology. The presence of different clinical phenotypes and courses is associated with diversity in autoantibody production. Historically, the treatment of refractory forms of polymyositis and dermatomyositis has undergone significant dynamics. Data from various studies have been published that show a significant reduction in the symptoms of inflammation, but unfortunately some of these disease-modifying treatments could not be established in rheumatology practice as sufficiently effective. Limiting factors are the retrospective nature of these studies, as well as different inclusion and exclusion criteria. However, in recent years, more and more data have emerged that present rituximab as one of the promising molecules for the treatment of patients refractory to conventional synthetic disease-modifying antirheumatic agents We present a clinical case of a 40-year-old Caucasian man with onset of the disease – fever, asthenodynamia, muscle pain and weakness, pericardial and pleural effusions. The patient was treated with glucocorticoids, methotrexate, pulse therapies with methylprednisolone and cyclophosphamide, as well as pulse therapy with intravenous immunoglobulins. Due to the temporary effect of the treatment and the relapse of the disease, the patient was started on mycophenolate mofetil therapy (instead of methotrexate). However, a new peak in disease activity was reported, necessitating resumption of pulse therapies with methylprednisolone and cyclophosphamide. Due to the refractory course of the disease, the patient was treated with rituximab after signed informed consent. A significant reduction in disease activity and a good clinical and therapeutic effect were reported.

ТЕЧЕНИЕ IgA-НЕФРОПАТИИ У ДЕТЕЙ И ОГРАНИЧЕННЫЕ ВОЗМОЖНОСТИ ИММУНОСУПРЕССИВНОЙ ТЕРАПИИ

It is believed that IgA nephropathy (IgAN) in childhood is predominantly manifested by hematuria with episodes of macrohematuria and has a relatively favorable course. The purpose of this research was to analyze the frequency of the use of mycophenolate mofetil (MMF) in children with IgAN in the Nephrology Department of the National Medical Research Center for Children’s Health (Moscow, Russia) and to evaluate the results of treatment in terms of the severity of proteinuria and the presence of a decrease in renal function by glomerular filtration. Materials and methods used: to assess the clinical course, histological features and kidney function during therapy, Authors analyzed the results of 737 biopsies performed in 2018-2022. Results: 126 biopsy specimens with predominant IgA deposition and mesangial proliferation and/or crescents were identified, 20 of them were excluded from further analysis due to the clinical picture of IgA vasculitis. 17 (16% of the remaining 106) patients had nephrotic-level of proteinuria prior to the biopsy, 11 had a history of acute kidney injury and 9 had a persistent decrease in glomerular filtration renal function. Steroid therapy with prednisolone at a dose of 0.5 to 1 mg/kg was carried out in 21 children, 14 (66.7%; CI 45.4-84.1%) of them had relapse or resistance. MMF therapy was started in 16 (11 boys and 5 girls) patients, median age of the therapy initiation was 13.4 [7.9; 15.3] y/o, 6 had a decrease in glomerular filtration rate (GFR) in the range of 64 to 85 ml/min. Kidney biopsy specimens were ere scored according to the Oxford classification MEST-C criteria. During the follow-up period (median 27.6 [20.0; 49.4] months), 14 (88% CI; 66-98) of 16 achieved complete (10) or partial remission, 2 patients had proteinuria of more than 1 g/l. Of 56 patients (median age 13.3 [9.6; 14.9] months) with a follow-up period of more than 6 months, a decrease in GFR was recorded in 5 (31.3%; CI 12.5-55.5) patients on MMF therapy and 4 (22.2%; CI 7.5-44.3) patients who received only a course of steroids and a single one (4.5%; CI 0.3-18.5) who received ACE inhibitor only. Analysis of biopsy results showed an increased risk of reduced GFR in patients with tubular atrophy. Conclusion: MMF therapy may have limited efficacy for proteinuria in IgAN though it does not prevent the GFR decline.

Efficacy and safety of multi-target therapy in children with lupus nephritis.

To analyze the efficacy and safety of multi-target therapy in children with lupus nephritis (LN). In our retrospective study from January 2009 to December 2021, the multi-target therapy of glucocorticoids, MMF and tacrolimus was adopted as induction therapy or re-induction therapy for 36 LN children who had combined proliferative and membranous LN or for who were ineffective to combination therapy of glucocorticoids with IV-CYC or MMF for at least 6 months. The clinical and pathological data were collected and analyzed. The levels of 24-h urinary protein, anti-dsDNA antibody and SLE disease activity index were decreased, while the levels of albumin and complement 3 were increased after multi-target therapy. More than 90% of LN children achieved partial or complete remission within 6 months. In terms of adverse effects, there was no significant difference between the level of eGFR before and after multi-target therapy. During the follow-up period, four children had infection, two children had hyperuricemia, and one child had liver dysfunction. All of them improved after symptomatic therapy. Multi-target therapy could be an effective treatment option with minimal adverse effects for LN children who are refractory to initial first-line induction therapies or had combined proliferative and membranous LN. The multi-target therapy of glucocorticoids, mycophenolate mofetil and tacrolimus was adopted in 36 children with lupus nephritis. Multi-target therapy could be an effective treatment option for lupus nephritis children who are refractory to initial first-line induction therapies or had combined proliferative and membranous lupus nephritis. Adverse effects of multi-target therapy were infrequent and minimal that can be improved by symptomatic therapy.

Combination Therapy of Low-dose Steroids, Tacrolimus and Mycophenolate Mofetil in Primary Membranous Nephropathy: A Single-center Retrospective Cohort Study

ABSTRACT Background: Primary membranous nephropathy (pMN) is the most common pathological type of nephrotic syndrome in adults. Therefore, it is imperative to find a better combination therapy with fewer adverse effects for patients with pMN. Methods: This study enrolled 84 patients with biopsy-proven pMN and nephrotic syndrome. Thirty patients in the low-dose multitarget regimen (LDMT) group received low-dose glucocorticoids along with tacrolimus and mycophenolate mofetil, and 54 patients in the prednisone plus intravenous cyclophosphamide regimen (PC) group received corticosteroids plus intravenous cyclophosphamide. The clinical efficacy and safety of the LDMT and PC regimens in treating pMN in adults were analyzed and compared. Results: The cumulative complete remission rate was 6.67%, 56.30%, and 83.14% at the 6th, 12th, and 24th month after treatment in the LDMT group, and 16.67%, 60.84%, and 81.02% in the PC group, respectively (P = 0.620). The generalized estimating equation analysis showed that the longer the treatment duration, the better the improvements in serum albumin and urinary protein levels, and hyperlipidemia (P = 0.0001). However, the serum creatinine levels in both groups remained stable during the treatment period. Meanwhile, the relapse rates were comparable between the two groups (21.43% vs. 22.00%, P = 0.953). Moreover, patients in the LDMT group showed fewer adverse events than those in the PC group (46.67% vs. 72.22%, P = 0.020). Conclusions: These data indicated that the low-dose multitarget regimen, which might be an alternative treatment choice for patients with pMN, had a more favorable safety profile and non-inferior efficacy compared with prednisone plus intravenous cyclophosphamide.

Safety and Efficacy of Inebilizumab in AQP4+ NMOSD Participants with History of Immunosuppression Treatment Prior to N-MOmentum Study (P13-5.003)

Safety and Efficacy of Inebilizumab in AQP4+ NMOSD Participants with History of Immunosuppression Treatment Prior to N-MOmentum Study (P13-5.003)

Meta-analysis of the effectiveness of relapse prevention therapy for myelin-oligodendrocyte glycoprotein antibody-associated disease.

Approximately 40% of adults and 30% of children with Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) experience a relapsing course, but the optimal relapse prevention therapy remains unclear. A meta- analysis was conducted to investigate the efficacy of azathioprine (AZA), mycophenolate mofetil (MMF), rituximab (RTX), maintenance intravenous immunoglobulin (IVIG), and tocilizumab (TCZ) in prevention of attacks in MOGAD. English and Chinese-language articles published from January 2010 to May 2022 were searched in PubMed, Embase, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CQVIP). Studies with fewer than three cases were excluded. Meta-analysis of the relapse-free rate, the change of annualized relapse rate (ARR)and Expanded Disability Status Scale (EDSS) scores before and after treatment, and an age subgroup analysis was performed. A total of 41 studies were included. Three were prospective cohort studies, one was an ambispective cohort study, and 37 were retrospective cohort studies or case series. Eleven, eighteen, eighteen, eight, and two studies were included in the meta-analysis for relapse-free probability after AZA, MMF, RTX, IVIG, and TCZ therapy, respectively. The proportions of patients without relapse after AZA, MMF, RTX, IVIG, and TCZ were 65% [95% confidence interval (CI):49%-82%]), 73% (95%CI:62%-84%), 66% (95%CI:55%-77%), 79% (95%CI:66%-91%), and 93% (95%CI:54%-100%), respectively. The relapse-free rate did not significantly differ between the children and adults treated with each medication. Six, nine, ten, and three studies were included in the meta-analysis for the change of ARR before and after AZA, MMF, RTX, and IVIG therapy, respectively. ARR was significantly decreased after AZA, MMF, RTX, and IVIG therapy with a mean reduction of 1.58 (95%CI: [-2.29--0.87]), 1.32 (95%CI: [-1.57--1.07]), 1.01 (95%CI: [-1.34--0.67]), and 1.84 (95%CI: [-2.66--1.02]), respectively. The change in ARR did not significantly differ between children and adults. AZA, MMF, RTX, maintenance IVIG, and TCZ all reduce the risk of relapse in both pediatric and adult patients with MOGAD. The literatures included in the meta-analysis were mainly retrospective studies, so large randomized prospective clinical trials are needed to compare the efficacy of different treatments.

Therapeutic outcomes of mycophenolate mofetil and glucocorticoid in thyroid-associated ophthalmopathy patients.

To analyze the efficacy of mycophenolate mofetil (MMF) and glucocorticoid administration in patients with thyroid-associated ophthalmopathy (TAO). Sixty patients with moderate to severe TAO treated in Jingzhou Central Hospital from January 2022 to June 2022 were selected and enrtolled in this study. The subjects were divided into experimental group (n=30) and control group (n=30) based on the random number table method. Glucocorticoid pulse therapy was provided in the control group, while MMF was given in the experimental group on the basis of Control group. Clinical activity score (CAS), quality of life (QOL), visual acuity, eyelid fissure width, intraocular pressure, and degree of exophthalmos were observed at the time of admission and at the 12th week and 24th post-treatment weeks. We compared the immune function (TRAb, IL-6, and CD4+/CD8+) of the two groups pre-treatment and 24 weeks post-treatment, and evaluated the clinical therapeutic effect. The clinical effective rates at 12 and 24 weeks in the experimental group were higher (73.3% and 83.3%) than those in the control group (46.7% and 60.0%) (P <0.05). After 12 weeks of treatment, patients' CAS scores, and bilateral lid fissure width decreased and right eye visual acuity increased in the control group compared with those before treatment (P < 0.05); further, after 24 weeks of treatment, patients' QOL scores and bilateral visual acuity increased and CAS scores, bilateral lid fissure width and proptosis decreased compared with those before treatment, and patients' QOL scores, CAS scores and bilateral proptosis improved more than those at 12 weeks of treatment (P <0.05). Additionally, greater improvements were observed in the patients' QOL and CAS scores, and proptosis after 24-week treatment than after 12-week treatment (P<0.05). In the experimental group, the QOL score and binocular visual acuity increased, whereas the CAS score, intraocular pressure, lid width, and proptosis decreased after 12 weeks of treatment as compared to the values of these parameters in the pre-treatment period (P < 0.05); after 24 weeks of treatment, greater improvements were established in the ocular-related indexes improved compared to the pre-treatment period and after 12 weeks of treatment (P < 0.05). After 12 weeks of treatment, the patients in the experimental group had more considerable improvements in the right visual acuity, right intraocular pressure, and left lid fissure width than the control group (P < 0.05); at 24 weeks of treatment, patients in the experimental group had greater improvements in the QOL score, bilateral visual acuity, intraocular pressure, bilateral lid fissure width, and bilateral proptosis than the control group (P < 0.05). No significant differences were found in the values of TRAb, IL-6, and CD4+/CD8+ between the two groups before treatment (P>0.05); the values of TRAb, IL-6, and CD4+/CD8+ in the experimental group was significantly lower than those before treatment and in the control group after 24weeks of treatment. (P>0.05). No statistically significant difference was observed in the incidence of liver damage and menstrual disorders between the two groups during the 24 weeks of treatment (P>0.05). The combination of oral MMF and glucocorticoid shock therapy is an effective drug for the treatment of patients with moderately active TAO.

The Combination Therapy of Glucocorticoids, Tacrolimus, and Mycophenolate Mofetil in Primary Membranous Nephropathy Coexisting with Type 2 Diabetes Mellitus: A Retrospective Study

ABSTRACT Background: Primary membranous nephropathy (pMN) is treated with glucocorticoids or immunosuppressive agents, depending on the disease severity. However, treating pMN with type 2 diabetes mellitus (T2DM) remains challenging. Methods: We retrospectively collected and analyzed the data of patients diagnosed with pMN and T2DM. The low-dose multitarget regimen consists of prednisone (10 mg/d), tacrolimus (0.05 mg/kg/d, blood concentration 5–10 ng/mL), and mycophenolate mofetil (1 g/d); The cyclophosphamide (CTX) regimen consists of prednisone (initial dose 1 mg/kg/d) and CTX (0.8–1.0 g/month, cumulative dose 6–9 g). Results: Sixty-seven patients were diagnosed with pMN and T2DM, and 28 were enrolled in this study, with 14 cases each in the low-dose multitarget and CTX groups. Urinary protein excretion decreased significantly in both groups after treatment, which was significantly greater in the low-dose multitarget group than that in the CTX group (2 months: −4800.48 ± 3002.65 mg/24h versus −1663.32 ± 4113.98 mg/24h, P −BH = 0.045; 12 months: −7289.25 ± 2520.92 mg/24h versus −4512.79 ± 3448.85 mg/24h, P −BH = 0.044). Serum albumin levels increased more in the low-dose multitarget group than in the CTX group, although the difference was not significant. Patients treated with glucocorticoids plus CTX had worse glycemic control in two months. Conclusion: The combination of glucocorticoids, tacrolimus, and mycophenolate mofetil was effective for treating pMN with T2DM and not inferior to the CTX regimen in proteinuria reduction. Further studies are needed to confirm the regimen's influence on blood glucose and long-term efficacy.

Mycophenolate mofetil–induced hyperlipidemia with cutaneous manifestations

We report a case of a 49 year old woman who developed biopsy-proven xanthomas on her hands and arms after initiation of Mycophenolate mofetil therapy for systemic lupus erythematosus (SLE) and subsequently went into remission upon cessation of the medication.