Use Of Mycophenolate Mofetil Research Articles

Bortezomib Maintenance After Allogeneic Transplantation in Newly Diagnosed Myeloma Patients Results in Decreased Incidence and Severity of Chronic GVHD

Allogeneic hematopoietic cell transplantation (HCT) has curative potential in myeloma but remains hampered by high rates of relapse and chronic graft-versus-host disease (GVHD). We hypothesized that bortezomib (BTZ) as maintenance therapy after allo HCT could not only decrease the incidence of relapse but also the incidence and severity of chronic GVHD. The primary endpoint of this study was to determine whether BTZ maintenance decreases the incidence and severity of chronic GVHD using National Institutes of Health (NIH) criteria. The secondary endpoints were to determine the immunosuppression burden, organ involvement and survival (overall survival, progression-free survival) in patients either receiving or not receiving BTZ. In this retrospective study, we compared the outcome of 46 myeloma patients who received BTZ after upfront tandem auto-allo HCT between 2008 and 2020 to 61 patients without maintenance. We explored the impact of BTZ maintenance on incidence and severity of chronic GVHD using the 2014 NIH criteria. At 2 years, incidences of overall (61.2% versus 83.6%; P=.001), and moderate/severe chronic GVHD (44.5% versus 77.0%; P=.001) were significantly lower in BTZ recipients who had less mouth (43% versus 67%; P=.018) and eyes (9% versus 41%; P=.001) involvement at initial diagnosis. We report a lower use of systemic steroids (45.1% versus 76.4%; P < .001), mycophenolate mofetil (15.5% versus 28.2%; P=.031) and tacrolimus (34.5% versus 70.6%; P < .001) in BTZ recipients. Probability of being alive and off systemic immunosuppressants at 3 years was 77% in BTZ recipients and 56% in controls (P=.046). To date, there is no difference in survival between both groups. In summary, BTZ maintenance improved incidence and severity of chronic GVHD and should be considered as a valid option in myeloma patients receiving upfront tandem auto-allo HCT.

Off-label use of mycophenolate mofetil in immune-mediated diseases

Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

Long-term results of mycophenolate mofetil vs. azathioprine use in individuals with autoimmune hepatitis

We have shown previously that mycophenolate mofetil (MMF) might be used as first-line treatment instead of azathioprine (AZA) in individuals with autoimmune hepatitis (AIH). Herein, we present our long-term prospective data on response and outcome after first-line therapy with MMF in treatment-naïve individuals with AIH, as similar data are missing. During the 21 years of the study, 292 individuals with AIH were included (females: 213; median age: 59 [17-85] years). Patients received either prednisolone 0.5-1mg/kg/day alone (n= 19) or in combination with AZA 1-2mg/kg/day (n= 64) or MMF (n= 183). The tapering schedule of prednisolone was identical between groups. We assessed the rates of complete biochemical response (CBR) at 6 months, 12 months, and the end of follow-up; non-response (4 weeks of treatment); CBR off prednisolone; adverse effects; CBR off treatment; histological remission; and overall and liver-related mortality between the AZA and MMF groups. The MMF group had lower non-response (p= 0.02) and higher CBR rates at 12 months (86 vs. 71.8%; p <0.05) and the end of follow-up (96 vs. 87.2%; p= 0.03) than the AZA group. Treatment change was more frequent in the AZA group (43.7 vs. 11%; p <0.001), mostly because of intolerance, whereas MMF was proven safe (serious complications 3.8 vs. 18.8%; p= 0.0003). MMF-treated patients were more frequently eligible to stop immunosuppression according to the guidelines (p <0.05). Cirrhosis at diagnosis, age at diagnosis >60 years, and longer disease duration were independent predictors of liver-related mortality. MMF seems an efficient alternative first-line treatment option for AIH, bearing lower non-response at 4 weeks and higher CBR rates at 12 months and the end of follow-up than AZA. In addition, MMF was proven to be safe, leading more frequently to the eligibility for stopping immunosuppression according to the guidelines. For more than 40 years, azathioprine (AZA) has been considered the standard treatment for induction and maintenance of response in autoimmune hepatitis (AIH). However, treatment usually needs to be maintained for life, as relapses are common after AZA cessation. Therefore, alternative treatment options are needed. Herein, we showed that the use of mycophenolate mofetil (MMF) as an alternative first-line immunosuppressant was much more efficient in the long-term than AZA as attested by the lower non-response rates at 4 weeks and higher response rates at 12 months and the end of follow-up. Moreover, AZA-treated patients were more prone to change treatment because of intolerance, whereas MMF-treated patients were more often eligible to achieve treatment withdrawal.

Risk of malignancy in patients with psoriasis receiving systemic medications: A nested case-control study.

Large-scale, real-world studies on the side effects of systemic therapies (including biologics) in patients with psoriasis are limited. We aimed to calculate the risk of malignancy in patients with psoriasis who were treated with systemic medications. Nested case-control analyses were performed among psoriasis patients without a history of malignancy. We recruited 4188 patients with newly diagnosed psoriasis and successive malignancies, and 8376 matched controls from the National Health Insurance Research Database in Taiwan. The therapy duration was within 5 years before malignancy onset and further stratified into two groups according to the duration of medication usage. Multivariate conditional logistic regression adjusted for potential confounders was used to estimate malignancy risk associated with systemic treatments. Among psoriasis patients, long-term (> 12 months) treatment with cyclosporine increased the risk of malignancy compared with no exposure (odds ratio, 1.57; p= 0.01). Short-term (≤ 12 months) or long-term (> 12 months) use of other systemic treatments, including methotrexate, azathioprine, systemic retinoids, mycophenolate mofetil, sulfasalazine, etanercept, adalimumab, and ustekinumab, was not associated with an increased risk of malignancy in patients with psoriasis. Long-term treatment with cyclosporine increased the risk of malignancy in patients with psoriasis by 1.57-fold.

412.1: Lip Actinic Cheilitis and Its Relationship to Clinical Characteristics and Immunosuppression in Kidney Transplant Recipients

Introduction: Due to drug immunosuppression after kidney transplantation (KT), as well as factors such as chronic uremia and chronic sun exposure, Kidney Transplant Recipients (KTR) have a 46-fold increased incidence of Lip Cancer (LC). Because of the high prevalence of LC in KTR, there are concerns about its prevention, which can be accomplished by diagnosing Actinic Cheilitis (AQ) on lips, a potentially malignant oral lesion that can progress to LC. Aim: The purpose of this investigation was to see if there was a link between the clinical manifestations of AQ and the clinical profile of KTRs. Methods: Convenience sampling in a cross-sectional observational clinical study. An expert researcher completed the diagnosis and clinical staging of AQ in KTRs using Pointevin et al 2017 criteria and a clinical evaluation and photographic record of six different angulations of the lower lip were used to calibrate the researcher (Kappa intra-avaliador >0.8). Demographic data, time since KT, immunosuppressants, exposure to AQ risk factors such as alcoholism, smoking, chronic sun exposure, and exposure to volatile chemical agents, and history of positive serology for oncogenic viruses after KT were all obtained retrospectively from electronic medical records. For the association of variables, Chi-square and Macnemar tests were performed, with a significance value of (0.05). Results: The sample size was 48 (100%) KTR, with 29 people diagnosed with AQ (60.41 percent). Light-siknned KTR was linked with the most severe AQ staging in 9 subjects (18.75 percent; p=0.035). History of exposure to volatile chemical agents (16.33 percent; p=0.007), drunkenness (15.25 percent; p=0.008), and smoking (20.66 percent; p=0.05) were also risk factors for AQ. A history of prolonged sun exposure was linked to a higher severity of QA 22(45.83 percent; p<0.001). The prevalence of AQ was linked to the usage of tacrolimus 43 (89,58 percent; p<0.001) and azathioprine 11 (22,91 percent; p0.001). However, the use of Mycophenolate Mofetil was linked to the most severe cases of AQ in 7 patients (14.58 percent; p=0.05). Individuals who got sirolimus, on the other hand, showed less AQ expression, with 7 patients (14.58 percent; P=0.016) manifesting with lesser degrees. After TxR, positive Epstein-Barr Virus serology was linked to the existence of AQ 17 (35,41 percent; p=0.028). Conclusion: The presence and severity of AQ in KTR were linked to fair skin, chronic sun exposure, Epstein-Barr Virus infections, and the use of Mycophenolate Mofetil. Sirolimus appears to have a protective effect against the development of AQ. It is possible to select groups of patients at higher risk for AQ and, as a result, for LC using this clinical profile associated with the manifestation of AQ, allowing for prevention and early diagnosis. This study was approved by the Ethics and Research in Human Beings Committee under protocol CAAE12798019.3.0000.5417.

330.4: SARS-coV-2 Antibody Response to a Third Dose of Homologous mRNA Vaccination in Liver Transplant Recipients

Purpose: Liver transplant (LT) recipients have a decreased response to 2 doses of SARS-CoV-2 vaccine compared to the general population, so we aimed to understand the response to a third dose to inform vaccination strategies. Methods: LT recipients with 3 congruent mRNA vaccines and antibody levels pre- and post-dose 3 (D3) were included. Those who reported a prior COVID-19 diagnosis or used belatacept were excluded. The latest anti-spike antibody level collected between the second (D2) and third dose (D3) was compared to the antibody level at 1 month post-D3. Samples were tested with Roche Elecsys Anti-Sars-CoV-2 enzyme immunoassay (EIA) (positive ≥0.8 U/mL) or EUROIMMUN EIA (positive ≥1.1 AU). Results: 149 participants completed 3 congruent doses of BNT162b2 (54%) or mRNA-1273 (46%) vaccines between 5/15/2021 - 11/20/2021. The median (IQR) time of latest pre-D3 antibody collection was 119 (92, 179) days post-D2. The median time of 1-month post-D3 antibody collection was 30(26, 33) days. The median time between D2 and D3 was 168 (149-188) days. Overall, 116/149 (78%) had a seropositive response pre-D3, and 141/149 (95%) were positive post-D3 (Figure 1). Among the 116 seropositive pre-D3, 116/116 (100%) remained seropositive post-D3. Among the 33 seronegative pre-D3, 25/33 (76%) converted to seropositive post-D3. Risk factors that were statistically significantly associated with negative post-D3 were mycophenolate mofetil use (75% vs 27%, p=0.009), BNT162b2 series (100% vs 52%, p=0.008), and seronegativity pre-D3 (100% vs 18%, p<0.001). Conclusion: LT recipients that were positive or negative pre-D3 had an excellent response to a third dose of mRNA vaccine, which is beyond what has been shown in other solid organ transplant recipients. Investigation in immunogenicity remains essential to protect vulnerable groups and guide policy. Figure: Antibody levels of latest pre-D3 versus 1 month post-D3, categorized by assay performed. The median (IQR) anti-RBD levels increased from pre to post-D3 by 12.9-fold (194 U/mL to 2500 U/mL), and median (IQR) anti-S1 levels increased by 4.5-fold (1.99 AU to 8.94 AU). The reference line delineates negative levels for anti-RBD (<0.8 U/mL) and anti-S1 (<1.1 AU) EIA. National Institute of Diabetes and Digestive and Kidney Diseases: T32DK007732 (Dr. Chang), T32DK007713 (Dr. Alejo), F32DK124941 (Dr. Boyarsky), K01DK114388 (Dr. Levan), K01DK101677 (Dr. Massie), and K23DK115908 (Dr. Garonzik-Wang). Johns Hopkins Pearl M. Stetler Research Fund. National Institute of Allergy and Infectious Disease: K23AI157893, U01AI138897-S04 (Dr. Werbel), and K24AI144954,U01AI138897 (Dr. Segev). Ben-Dov family. Trokhan Patterson family.

412.9: Association of Skin Cancer With the Use of Azathioprine And Mycophenolate Mofetil in Kidney Transplant Recipients

412.9: Association of Skin Cancer With the Use of Azathioprine And Mycophenolate Mofetil in Kidney Transplant Recipients

Risk Factors for Development of Pneumatosis Intestinalis after Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Case-Control Study

The significance of pneumatosis intestinalis (PI) in pediatric patients following hematopoietic stem cell transplantation (HSCT) is poorly understood. A knowledge gap remains with respect to the etiology, risk factors, and evidence-based treatment of these patients. As a result, management is frequently based on each center's clinical practice, without standardization across treatment centers. In this single-center trial, we aimed to validate both previously proposed and additional risk factors for the development of PI and to examine our management and outcomes for these patients. We performed a retrospective case-control study examining risk factors for the development of PI in pediatric HSCT patients at a single tertiary referral children's hospital. We used univariate and multivariable conditional logistic regression analysis to explore differences in pharmacologic and other transplantation-specific risk factors. Between 2012 and 2019, PI was diagnosed in 212 patients at our pediatric hospital, of whom 42 were HSCT recipients. The majority of patients (88%; n=37 of 42) with PI were diagnosed by X-ray. Eighteen patients (43%) were asymptomatic and diagnosed incidentally after imaging was obtained for standard post-transplantation surveillance or other nonrelated indications. All patients with PI were hospitalized and placed on strict bowel rest while receiving parenteral nutrition and antibiotics. Recurrence of PI occurred in 4 patients (10%) following their initial diagnosis. Increased doses of steroid exposure within 30 days of PI diagnosis (odds ratio [OR], 5.7; 95% confidence interval [CI], 2.1 to 15.3; P=.0006), presence of grade II-IV gastrointestinal acute graft-versus-host disease (GVHD) (OR, 5.3; 95% CI, 1.0 to 28.1; P=.05), and receipt of >50% of total daily nutrition by nasogastric (NG) tube feeds (OR, 22.0; 95% CI, 1.3 to 370.2; P=.03) were identified as independent risk factors for the development of PI. Intensity of the conditioning regimen, exposure to total body irradiation, stem cell source, donor type, HLA matching, use of mycophenolate mofetil, and presence of bacterial or viral infection at the time of PI diagnosis were not demonstrably associated with the development of PI in our study. We conclude that development of asymptomatic PI is a benign condition following HSCT, and that the risk for PI is increased in patients with gastrointestinal GVHD, patients receiving steroid therapy, and patients relying on supplemental NG tube feeds for at least one-half of their total daily nutrition.

Experience with the use of mycophenolate mofetil in juvenile idiopathic inflammatory myopathies.

The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs). Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment. Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported. Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM.

Effectiveness of delayed second dose of AZD1222 vaccine in patients with autoimmune rheumatic disease

There is paucity of data on extended dosing interval between two doses of AZD1222 (AstraZeneca) in patients with Autoimmune Rheumatic Diseases (AIRD). We aimed to study the humoral response and rate of breakthrough infections between the two groups who had received the second dose of vaccine at 4 weeks (Group 1) and 10–14 weeks (Group 2). From established cohort [COVID-19 vaccination cohort from CARE(CVCC)] of vaccinated patients with AIRD, those who had received AZD1222 were included and divided into two groups. Anti-Receptor Binding Domain (RBD) antibodies (IU/ml) were measured 1 month after the second dose. Its predictors and rate of breakthrough infections were studied. Four hundred ninety-five patients with AIRD were included in this study. Group 2 had higher anti-RBD antibody titres [1310.6 (±977.8) and [736 (±864.7), p = 0.0001. On univariate analysis, presence of Diabetes Mellitus; use of Methotrexate, Sulfasalazine, and Mycophenolate Mofetil; and vaccine interval were significantly associated with anti-RBD antibodies. Diabetes Mellitus and vaccine interval were independent predictors on multivariate analysis. Breakthrough infections were higher in Group 1 numerically on survival analysis but the difference was not significant (7.5% and 4.5%; log rank test: p = 0.25). In conclusion, increasing the gap between doses of the AZD1222 vaccine from 4 week to 10–14 weeks was found to be more beneficial in terms of antibody response in patients with AIRD. There was a trend towards higher breakthrough infections in the short interval group, supporting the antibody data.Key Points• There is paucity of data on effectiveness of increased dosing interval from 4-6 to 10-14 weeks for AZD1222 in patients with AIRDs• We observed a better humoral response with increased dosing interval with the interval and Diabetes Mellitus being independent predictors of the anti-RBD antibody levels• Breakthrough infections were numerically higher in the short interval group but the difference wasn't significant

Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort.

ObjectiveIn the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination.MethodsVolunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers.ResultsSamples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age.ConclusionThe response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.

Retroperitoneal fibrosis - diagnosis and treatment.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, often with nocturnal exacerbations and not responding to position changes. The disease is commonly associated with signs of systemic inflammatory response (malaise, fever, and anorexia and weight loss). Glucocorticoids are considered the cornerstone of the therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab have been reported as a valuable option mostly in case reports, cases series and small studies. These agents allowed to reduce cumulative dose of glucocorticoids and their adverse effects. Combined therapy is preferable for all patients who suffer from significant glucocorticoid- related toxicity or in cases where glucocorticoids alone are insufficient to treat the condition.

A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases

BackgroundWe conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs).MethodsThis was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome.ResultsCOVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5–20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region.ConclusionsImmunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Mycophenolate mofetil use is associated with reduced incidence of food allergy in liver transplanted children.

The incidence of food allergy in children following liver transplantation is high and the pathogenesis is still not known. We aimed to identify risk factors for development of food allergies in liver transplant children. 107 children and adolescents who underwent liver transplantation from 1999 to 2019 were included. Data were retrospectively collected from medical records included total and specific IgE, eosinophil cationic protein and eosinophil count 12 months after transplantation and at yearly follow up (median follow-up). 24/107 (22%) patients reported clinical food reactions. Median time from transplantation to debut of food allergy was 1.6 (IQR 0.6-3.3) years. Mycophenolate mofetil (MMF) was discontinued in 24/78 patients (31%) due to side effects. Children treated with MMF in addition to tacrolimus one year after transplantation reported less food allergy (12.5% vs. 37.8%, p=0.003) and sensitization to food allergens one year after transplantation (8.9% vs. 17.8%, p=0.02) than those not receiving MMF. Tacrolimus trough levels did not differ between the patients treated with MMF and those who were not. Treatment with MMF two years after transplantation was associated with less food allergy (p=0.001) and food sensitization (p=0.002), also when adjusted for age at transplantation (p=0.006 and p=0.03, respectively) or for use of basilixmab (p=0.015 and p=0.018, respectively). Basiliximab was also associated with less food allergy. Use of MMF one and two years after transplantation was associated with less food allergy and sensitization against food allergens. The effect of MMF was not due to reduced trough levels of of tacrolimus. An infographic is available for this article at: https://links.lww.com/MPG/C821.

POS-021 C4 COMPLEMENT DEFICIENCY AND TYPE III CRYOGLOBUINEMIA IN A PATIENT WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

POS-021 C4 COMPLEMENT DEFICIENCY AND TYPE III CRYOGLOBUINEMIA IN A PATIENT WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

Use of mycophenolate mofetil in patients with pediatric and adult primary nephrotic syndrome: information from a Japanese hospital claims database

BackgroundCurrent treatment for frequently relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome focuses on immunosuppressive therapies. Although the clinical guideline suggests the use of mycophenolate mofetil (MMF), limited information is available on patients with primary nephrotic syndrome who receive off-label treatment with MMF in Japan.MethodThe dose, treatment duration, previous treatment, and characteristics of primary nephrotic syndrome patients receiving MMF were investigated using data from a Japanese hospital claims database (April 2008–September 2021).ResultsData on 424 primary nephrotic syndrome patients receiving MMF (146 patients < 18 years old; 278 patients ≥ 18 years old) were captured. The most common initial daily doses of MMF capsules (% of patients < 18 and ≥ 18 years old) were 1000 mg (31.9%, 36.8%), 1500 mg (16.0%, 23.8%), and 500 mg (23.6%, 17.3%), and the most common maximum daily doses were 1000 mg (43.8%, 32.9%), 1500 mg (23.6%, 28.9%), and 2000 mg (6.3%, 16.2%). Most patients (97.9%, 99.3%) were treated with a daily dose of 2000 mg or less. Among patients < 18 years old, the younger the patient, the lower the dose. MMF was used for more than 1 year in 30.8% of patients < 18 years old and in 28.8% of patients ≥ 18 years old.ConclusionsOur study suggested that off-label use of MMF for primary nephrotic syndrome has increased since 2012 in Japan. The dose of MMF used in patients with primary nephrotic syndrome was generally within the approved dose range for lupus nephritis and transplant-related diseases in Japan.

Comparison of Long-Term Use of Low Dose Rituximab and Mycophenolate Mofetil in Chinese Patients With Neuromyelitis Optica Spectrum Disorder

BackgroundSeveral studies have reported the efficacy and safety of rituximab (RTX) and mycophenolate mofetil (MMF) in neuromyelitis optica spectrum disorder (NMOSD). This study aimed to evaluate the efficacy and safety of long-term use of low-dose RTX and MMF in Chinese patients with NMOSD.MethodsWe retrospectively reviewed data from patients with NMOSD in our hospital. The enrolled patients were administrated different immunosuppressive agents. We accessed annual relapse rate (ARR), neurological disability (Expanded Disability Status Scale, EDSS), time to the next relapse, and adverse events.ResultsEDSS and ARR were both reduced after RTX and MMF treatment. Kaplan-Meier analysis indicated that patients treated with RTX had a longer time to next relapse compared other immunosuppressive agents before RTX (log-rank test: p < 0.001). Furthermore, we evaluated the change of EDSS and ARR in RTX and MMF, and patients treated with RTX showed a better reduction. Eleven relapses from seven patients in group RTX and 20 relapses from 14 patients in group MMF were reported during follow-up.ConclusionLong-term using of low dose of RTX and MMF were effective and tolerable in Chinese patients with NMOSD. Compared with MMF, RTX showed a better way to reduce the ARR.

Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Remodeling of extracellular matrix cell elements in Peyronie's disease experimentally induced by TGF-beta and treated with mycophenolate mofetil

ABSTRACT Introduction Peyronie´s disease(PD) is a common disease among men which causes tortuosity in the penis, making it difficult and sometimes even preventing sexual activity. PD corresponds to the presence of fibrotic disorder in the tunica albuginea of the corpus cavernosum.This disorder is characterized by excessive accumulation of collagen fibers and other components of the extracellular matrix(ECM).The metalloproteimases(MMP) are involved in the reinforcement and debilitation of many processes that influence the development of fibrosis. PD can be conducted initially with clinical treatment, but the literature does not show an adequate resolution of this condition. Mycophenolate mofetil(MMF) belongs to a class of immunosuppressants drugs and has been used to treat patients with some fibrotic disorders as retroperitoneal fibrosis. A previous study evaluating the use of Mycophenolate Mofetil showed an important improvement in the arrangement of collagen fibers after experimental induction of peyronie´s disease. This experimental model, where the penile anatomy of rats is similar to the men, promote the ability to study fibrosis at its various levels and the effects of new drug for penile rehabilitation. Objectives The aim of this research is to investigate the alterations in the elements of extracelular matrix promoted by the antifibrotic action of Mycophenolate Mofetil in rats with TGF-Beta induced peyronie-s disease Methods Thirty male Wistar rats will be used,divided into 6 groups.Group 1- control group. Group 2 - rats that will receive injection of saline in the tunica albuginea. Group 3- rats that will receive only injection of TGF-beta. Group 4- rats that will receive TGF-beta and will be treated with MMF during 7 daysy. Group 5- rats that will receive TGF-beta and will be treated with MMF por 30 days. Group 6- rats that will receive only MMF. All rats‘penises will be collected after euthanasia for histochimical assesmente of collagen fibers with picrossirius and immunohistochewmistry of metalloproteinases(MMP2, MMP3 and MMP9). Five random fields from the region of the tunica albuginea will bew captured for each penile sample with Olyvia software and measurements will be performed with ImageJ software of the elements of the extracellular matrix. To compare groups will be used the paired sample T test. Data will be checked for normality using th kolmogorov-Smirnov test. When non-parametric, the Kruskal-Wallis test followed by Dunn´s test will be used.Differences will be considered statiscally significant when p&amp;lt;0,05.This experimente was approved and will be conducted according to the ethics committee rules on the use of animals. Hypothesis MMF promotes na improvement in fibrotic disorder preventing peyronie´s disease. Disclosure Work supported by industry: no.

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis.

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis.