Mycophenolate Therapy Research Articles

Impact of Immunosuppressive Therapy, Vaccination, and Monoclonal Antibody Use With Outcomes in Liver and Kidney Transplant Recipients With COVID-19: A Retrospective Study.

Patients who have undergone solid organ transplantation are at an elevated risk of severe coronavirus disease (COVID-19) because of post-transplantation immunosuppressive therapy. However, optimization of vaccination, modification of immunosuppression, and implementation of monoclonal antibody (mAb) therapy in transplant recipients with COVID-19 is uncertain. A retrospective cross-sectional study was conducted on patients who underwent liver or kidney transplants and were diagnosed with COVID-19. The association of several vaccine doses, mycophenolate therapy, and mAB therapy with mortality outcomes after COVID-19 diagnosis (3 and 6 months), hospitalization, and length of hospital stay were assessed. This study included 255 patients with a median age of 59 (23-89) were included. Many COVID-19 vaccine doses were not associated with any outcome; however, patients with a liver transplanted with mycophenolate had higher 3-month (19% vs. 0%; p = 0.02) and 6-month (21% vs. 0%; p = 0.01) mortality rates than those who did not. In addition, transplant recipients who received mAb therapy for COVID-19 were less likely to be hospitalized (37% vs. 68%; p < 0.001). For organ transplant recipients with COVID-19, vaccination alone may not be an optimal strategy for preventing serious outcomes. Rather, the types of organ transplant, immunosuppressive therapy (particularly mycophenolate), and COVID-19 treatment strategy should be synergistically considered to promote an optimal therapeutic dynamic for a vulnerable population.

Mycophenolate Mofetil for the Treatment of Warm Autoimmune Haemolytic Anaemia Post-Rituximab Therapy: A Case Series.

Warm autoimmune haemolytic anaemia (wAIHA) is an acquired haemolytic disorder most commonly treated with a combination of corticosteroids, rituximab and/or splenectomy. Third-line therapies for refractory cases include immunosuppressive agents. Mycophenolate mofetil is frequently used in these scenarios, although its use is supported by small studies and anecdotal evidence rather than large-scale data. We describe three cases of refractory warm autoimmune haemolytic anaemia successfully treated with mycophenolate mofetil. Case 1: A persistent case of autoimmune haemolytic anaemia in a 56-year-old was ultimately managed with mycophenolate mofetil, leading to successful steroid tapering and stable haemoglobin levels without relapse. Case 2: A woman with a complex oncological history, including lymphoma and breast cancer, achieved remission with mycophenolate therapy, maintaining stability post-steroid treatment. Case 3: Mycophenolate proved effective for a 63-year-old with cirrhosis after recurrent autoimmune anaemia and deep vein thrombosis, enabling cessation of steroids and maintaining remission. Management of this condition can be challenging and balancing the available treatments is crucial to reduce potential complications from long-term therapies that appear to be ineffective. Our case series demonstrates anecdotal experience on successful use of mycophenolate mofetil for complex refractory cases of wAIHA. Warm autoimmune haemolytic anaemia can be a challenging condition to manage. Refractory cases that are steroid-dependent can benefit from trialling steroid-sparing agents such as mycophenolate.Anti-CD20 agents such as rituximab can be very effective in refractory cases, however there is a small percentage of patients that might not be responsive to this monoclonal antibody.Autoimmune haemolytic anaemias can be frequently complicated by thrombotic events, and part of the backbone treatment is establishing good thromboprophylaxis.

Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial

IntroductionSeveral studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis...

PO-04-050 ROLE OF FDG-PET CT IN GUIDING THERAPY FOR RELAPSING AND REMITTING MYOCARDITIS

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan is considered as a goal standard test for the diagnosis of myocarditis. Low intensity FDG uptake of the lateral wall without perfusion abnormalities is considered to be a variant of normal. It is imperative to correlate myocardial and pericardial abnormality revealed by myocardial FDG uptake with the signs and symptoms of myocardial disease, as it tends to be overlooked. However, recognition of possible underlying disease will support further patient management to avoid complications due to the disease. While the utility of FDG PET in the diagnosis of myocarditis and initiation of therapy is well documented, there is no consensus in the preferred strategy for monitoring the response to therapy. To present a case highlighting the utilization of FDG PET in guiding the therapy for relapsing/remitting myocarditis. N/A A 55yo male presented with new onset HF with LVEF of 15-20% at the time of index presentation. He underwent cardiac catheterization which showed non-obstructive CAD. He was diagnosed with NICM and was discharged home on GDMT with a wearable external defibrillator. His outpatient work-up with FDG PET imaging showed normal perfusion with FDG uptake involving the proximal, mid inferolateral, and lateral region with a SUV-max of 3.4. Biopsy was determined to be too high-risk and was therefore not pursued. He was diagnosed with chronic idiopathic myocarditis with possible isolated cardiac sarcoidosis and started on methotrexate (MTX). Prednisone was considered but decided against due to comorbid diabetes. His follow up FDG PET in 6 months reported an increase in the SUV max to 4.2 and involvement of lateral base in addition to the mid-inferolateral region [Figure 1(a),(b)]. Due to lack of improvement, the patient was switched from MTX to mycophenolate. Repeat 6 month follow up FDG PET showed resolution of myocarditis with SUV-max of 2.6 [Figure 1(c),(d)] and patient was taken off immunosuppressive therapy. Six-month follow-up FDG PET was unchanged and was thus reassuring. One year later, the patient relapsed with focal FDG uptake of entire lateral and mid and basal inferolateral walls with an SUV max of 11.2 on imaging [Figure 1(e),(f)]. The patient was consequently restarted on mycophenolate therapy. This case highlights the relapsing and remitting clinical course of a patient with FDG-PET uptake in myocardium which was treated with immunosuppressive therapy with serial FDG-PET guidance.

Focal Segmental Glomerulosclerosis and Renal Failure Secondary to Protein Kinase C Delta Deficiency in an Adolescent Male

Introduction: The autoimmune lymphoproliferative syndrome (ALPS)-like condition, Protein Kinase C-delta (PRKCD) deficiency, is associated with a lupus-like presentation, recurrent infections, and reduced B-cell function with hypogammaglobulinemia in addition to prominent lymphadenopathy and splenomegaly. Renal manifestations previously reported include nephrotic syndrome and glomerulonephritis. Focal segmental glomerulosclerosis (FSGS) and significant end-stage renal disease requiring dialysis have not been previously described in those with PRKCD deficiency.Case Study: We describe a now 21-year-old male of Palestinian descent with consanguineous parents who initially presented at 15 months of age with arthritis, splenomegaly, neutrophilic rash, and recurrent fevers. At 7 years of age, the patient was hospitalized with hepatosplenomegaly, diffuse adenopathy, and post-obstructive pneumonitis secondary to hilar adenopathy. He was subsequently given a diagnosis of presumed ALPS, although FAS mutation testing was negative, and started on mycophenolate with improvement in symptomology. He underwent additional comprehensive genetic testing when he was 18 years old with results revealing a novel homozygous PRKCD variant (c. 1872 1 G > A) leading to a presumed donor splice site defect. [Display omitted] Starting at 19 years of age, the patient was noted to have a steadily rising serum creatinine and profound proteinuria. Kidney biopsy revealed chronic immune complex glomerulonephritis with capillary loop and mesangial immune deposits and changes consistent with secondary FSGS. (Figure 1A&B). He was started on an angiotensin-converting enzyme (ACE) inhibitor for antiproteinuric effects, though this was discontinued due to persistent hyperkalemia. A subsequent renal biopsy performed 5 months later in the clinical setting of rapid deterioration of GFR and worsening proteinuria showed worsening FSGS with prominent podocytopathy (Figure 1 C&D). Mycophenolate and IVIG therapy were discontinued given a lack of efficacy and to preserve renal function. Unfortunately, his creatinine continued to rise, and he progressed to end-stage renal disease necessitating dialysis. He is currently being considered for kidney transplantation. ConclusionSevere FSGS leading to renal failure is an uncommon diagnosis in adolescents and has not previously been described in those with PRKCD deficiency. Our case thus broadens the phenotypic and pathologic renal manifestations of the disorder and emphasizes the need for comprehensive multidisciplinary care of individuals affected by ALPS-like conditions.

A Case of Idiopathic Immunotherapy-Responsive Autoimmune Hemichorea (P9-5.031)

<h3>Objective:</h3> We describe a case of relapsing hemichorea in a patient without imaging or laboratory abnormalities who had excellent responsiveness to immunotherapy. <h3>Background:</h3> Hemichorea is a hyperkinetic movement disorder characterized by involuntary, arrhythmic dance-like movements affecting one side of the body. Acute or subacute adult-onset hemichorea without structural lesion or metabolic derangement suggests a possible autoimmune cause. We present the case of a 74-year-old woman with a history of anxiety and mild cognitive decline who developed rapid onset of hemichorea with concurrent encephalopathy. <h3>Design/Methods:</h3> The patient was identified through direct care. The report was formulated through chart review. <h3>Results:</h3> The patient received her second dose of the primary COVID-19 mRNA vaccine series six weeks prior to symptom onset. One day prior to symptom onset she developed a mild erythematous upper extremity rash that was responsive to antibiotics. Over several days she developed left-sided hemichorea, encephalopathy, and transient auditory and visual hallucinations. Brain MRI, EEG, brain PET, and body PET-CT were unremarkable. Serum and CSF inflammatory markers were normal. Extensive and repeated serum and CSF testing for neuronal autoantibodies was negative. Serum autoantibody testing revealed only a positive anticardiolipin IgM, which was subsequently negative after multiple repetitions. She was empirically treated with 2 g/kg of IVIg and had near-complete resolution of her hemichorea and modest improvement in encephalopathy. Five months later she relapsed with an identical presentation and again received 2 g/kg of IVIg, which substantially decreased but did not fully resolve her hemichorea. She achieved remission following an outpatient course of methylprednisolone 750 mg IV weekly for nine weeks. Four months after treatment she relapsed again, this time achieving remission after repeated IV steroids and initiation of mycophenolate maintenance therapy. <h3>Conclusions:</h3> This case demonstrates the importance of considering autoimmune etiologies of hyperkinetic movement disorders and empiric immunotherapy in patients with an unrevealing workup. <b>Disclosure:</b> Dr. Rodin has nothing to disclose. Dr. Venna has nothing to disclose. The institution of Dr. Balaban has received research support from Biogen.

Immunosuppression Protocols in Intestinal and Multivisceral Transplantation—A Literature Review

Intestinal transplantation (IT) and multivisceral transplantation (MVT) are curative therapies for patients with intestinal failure and severe complications associated with total parenteral nutrition. High levels of immunosuppression are required to prevent acute cellular rejection (ACR) from the bowel. Studies regarding pre-treatment, induction, and post-transplant therapy have improved graft acceptance, reducing immunosuppression doses and infectious complications. However, the low rate of IT and MVT and the small number of specialized centers have resulted in a limited number of evidence-based immunosuppression protocols. We reviewed immunosuppression in IT and MVT to draw useful conclusions regarding the best protocol strategies for the induction, maintenance, and management of ACR. A review was performed using the PubMed database. Articles on immunosuppression protocols in IT and MVT that addressed graft rejection, infection, or survival, published between 2006 and 2022, were selected. A total of 690 articles were selected. Two researchers applied the inclusion and exclusion criteria and selected 14 articles independently. For induction, thymoglobulin, alemtuzumab, and basiliximab are the most frequently used immunosuppressants for induction. Classic maintenance therapy consists of a combination of corticosteroids and tacrolimus. Methylprednisolone with an increased tacrolimus dose is used most frequently to manage ACR. Depending on the receptor response, such as thymoglobulin, infliximab, adalimumab, or bortezomib, other immunosuppressants should be considered. There have been great advances in IT and TMV immunosuppression. We conclude that the gold standard immunosuppressive protocol is triple therapy, comprising induction with thymoglobulin, maintenance with steroids for a few months, and tacrolimus and mycophenolate therapy. Innovative approaches for treating intestinal rejection episodes with more appropriate drugs, such as infliximab, adalimumab, or bortezomib, are necessary.

Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21-11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine.

Corticosteroid-induced remission and mycophenolate maintenance therapy in granulomatous lymphocytic interstitial lung disease: long-term, longitudinal change in lung function in a single-centre cohort

AimThe aim of the study was to evaluate the response in lung function to different treatment regimens for common variable immunodeficiency patients with granulomatous lymphocytic interstitial lung disease (GLILD).MethodA longitudinal retrospective cohort study was carried out. Patients were divided into three groups. To assess the response to different treatments, we compared baseline lung function with post-treatment tests.Results14 patients with GLILD were included, seven of whom were treated with acute corticosteroids for a mean duration of 132±65 days. Spirometry results were unchanged, but there was a significant improvement in diffusing capacity of the lung for carbon monoxide (DLCO)% and transfer coefficient of the lung for carbon monoxide (KCO)% (median change in DLCO%=7%, p=0.04, and KCO%=13%, p=0.02). Relapse occurred in three out of seven patients. Five patients were treated with long-term mycophenolate mofetil (MMF) with/without corticosteroids for a mean duration of 1277±917 days. No changes were found in spirometry; however, there was a significant increase in DLCO% and KCO% (median change in each of DLCO% and KCO%=10%, p=0.04). Four patients on steroids with MMF successfully weaned the prednisone dose over 12 months. Four patients never received immunosuppression therapy. A significant decline was found in their lung function assessed over 7.5 years. The median reduction in the forced vital capacity (FVC)%, forced expiratory volume in 1 s (FEV1)% and DLCO% was 15%, 7% and 15%, equivalent to 2%, 1% and 2% per year, respectively.ConclusionCorticosteroids improve gas transfer in GLILD, but patients often relapse. The use of MMF was associated with long-term effectiveness in GLILD and permits weaning of corticosteroids. A delay in initiating and continuing maintenance treatment could lead to disease progression.

How Vaccinations Changed the Outcome of COVID-19 Infections in Kidney Transplant Patients: Single-Center Experience.

Kidney transplant recipients are a vulnerable population at risk of a life-threatening COVID-19 infection with an incidence of death four-times higher than in the general population. The availability of mRNA COVID-19 vaccines has dramatically changed the fate of this infection also within this fragile population. Transplanted patients have an impaired immunological response also to mRNA vaccines. In March 2021, however, we started a vaccination campaign. These preliminary results show that both the incidence of death and of hospitalization dropped from 13% to 2.4% and from 45% to 12.5% compared to the previous outbreaks reported by our group. In univariate analysis, two variables were associated with an increased risk of hospitalization: older age and dyspnea (p = 0.023, p < 0.0001, respectively). In multivariate analysis, dyspnea (p < 0.0001) and mycophenolate therapy (p = 0.003) were independently associated with the risk of hospitalization. The association was even stronger when the two variables were combined (p < 0.0001). Vaccinations did not reduce the incidence of COVID-19 infections among our transplanted patients, but provided certain protection that was associated with a significantly better outcome for this infection.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Severe Immune Thrombocytopenia (ITP) Following SARS-CoV-2 mRNA Vaccine in a Girl on Immunosuppressive Treatment and in Prolonged Stable Phase of ITP.

Rare cases of immune thrombocytopenia (ITP) occurring after SARS-CoV-2 mRNA vaccines have recently reached public attention. It has been reported in patients with previous ITP or other autoimmune diseases and in individuals with an apparent negative past medical history. The management and the outcome of these cases are still not well investigated and reported in the medical literature. A 23-year-old female with a past medical history of ITP, in stable complete remission for 3 years and on mycophenolate treatment received SARS-CoV-2 mRNA vaccine. She presented severe ITP recurrence with hemorrhagic symptoms after the second vaccine dose. A combined treatment with high-dose immunoglobulin and prednisone was successfully administered with a full recovery of platelet count. The patient remains in ITP remission and on mycophenolate therapy, five months later. At our Center, none of the other 76 adult “fragile patients” with ITP on immunosuppressive treatment who had received the SARS-CoV-2 mRNA vaccine, developed such a severe thrombocytopenic recurrence. Follow-up of large cohorts of patients receiving mRNA vaccine will answer the question as to whether it increases the risk of autoimmune conditions. So far, the benefits of the vaccination largely outweigh the risk of infection in these patients.

Increased Incidence of Clonal Hematopoiesis in Lung Transplant Recipients Involves DNA Damage Response Genes

Lung transplant recipients receive lifelong immunosuppression that includes a calcineurin inhibitor (tacrolimus or cyclosporine), an anti-proliferative agent (mycophenolate or azathioprine) and corticosteroids. They are also known to be at increased risk for a broad spectrum of adverse hematologic events. This includes relatively common complications such as neutropenia and other cytopenias, which occur in over half of patients, as well as rarer events such as de novo hematopoietic malignancy. Certain patterns of clonal hematopoiesis, the expansion of unique somatic clones in hematopoietic stem cells, are known to be associated with cytotoxic therapy and the development of hematologic malignancies. We hypothesized that the stress of transplantation and subsequent immunosuppression provides an environment whereby a unique pattern of clonal hematopoiesis emerges.To evaluate this hypothesis, we designed a custom panel of 59 genes using an error-corrected sequencing assay capable of detecting variant allele frequency (VAF) as low as 0.01. We characterized the overall burden and distribution of clonal hematopoiesis and compared differences among lung transplant recipients (n=73) and age-matched healthy controls (n=19). Clonal hematopoiesis was identified in 51/73 (69.9%) of lung transplant recipients. This was significantly higher than the frequency in the age-matched healthy controls (6/19,31.6% p=0.0071). Additionally, 27/51 (52.9%) of patients with clonal hematopoiesis had multiple variants. The increase in clonal hematopoiesis was mainly due to mutations in DNA damage response (DDR) genes (ATM, PPM1D, SRCAP or TP53), with 29/73 (39.7%) of lung transplant recipients carrying one or more mutation compared with 1/19 (5.3%) of age-matched healthy controls (5.3%, p=0.029). No significant difference in the frequency of clonal hematopoiesis due to non-DDR genes was also observed (48% vs. 26.3%, p=0.121).We first evaluated the relationship between clonal hematopoiesis and lung transplant indication. This is relevant, since interstitial lung disease (ILD), a common indication for lung transplantation, is associated with telomeropathies which are also linked to bone marrow failure and clonal hematopoiesis. However, the frequency of DDR clonal hematopoiesis in ILD patients (17/39, 44%) was similar to that observed in patients with COPD (9/20, 45%). We next investigated the association of immunosuppression with clonal hematopoiesis. Overall, 30/48 patients on mycophenolate (MPA) and 13/19 patients on azathioprine (AZA) had at least 1 clonal hematopoiesis mutation. We found no significant difference in overall clonal hematopoiesis frequency among patients on MPA vs. AZA. However, the frequency of DDR clonal hematopoiesis was significantly higher in patients on AZA (OR 4.04, 95% CI 1.22-13.38, p=0.022) than in patients on MPA. Moreover, when we assessed clonal hematopoiesis burden via Poisson regression, it was increased in patients receiving AZA (1.68, 95% CI 1.08-2.59, p=0.020) when compared to patients on MPA. All lung transplant recipients were maintained on tacrolimus but one, so associations with type of calcineurin inhibitor could not be assessed. Finally, we assessed clonal hematopoiesis in recipients who developed neutropenia (n=24) and found no significant association.To the best of our knowledge, we report the first evidence of increased clonal hematopoiesis in a solid organ transplant population. Our data indicate that azathioprine therapy is associated with the expansion of hematopoietic clones carrying variants in DDR genes. However, azathioprine therapy often represents a failure of MPA therapy, typically due to either hematologic or gastrointestinal toxicity. Therefore, the association noted might reflect MPA intolerance rather than azathioprine therapy. Nevertheless, prior studies show that treatment with genotoxic agents, such as chemotherapy or radiation therapy, provide a fitness advantage to hematopoietic stem/progenitor cells carrying DDR gene variants. Whether azathioprine vs. MPA therapy confers a similar fitness advantage is currently under investigation. Further investigation also is warranted to determine if the presence of clonal hematopoiesis influences lung transplant outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

1106. The incidence and risk factors associated with varicella zoster virus infection in kidney transplant recipients after 1-month acyclovir prophylaxis in a CMV preemptive therapy era

BackgroundVaricella zoster virus (VZV) infection is a well-known opportunistic infection in solid organ transplant recipients. Since the various strategies of the use of anti-herpetic drugs including ganciclovir or acyclovir have evolved, the epidemiology of VZV infection is changing. However, there are limited data on the recent incidence and risk factors of post-transplant VZV infection in popular preemptive ganciclovir era for CMV infection. We evaluated the incidence, risk factors and clinical characteristic of patients with development of post-transplant VZV infection in kidney transplant (KT) recipients after 1-month acyclovir prophylaxis in the hospital that adopted preemptive ganciclovir therapy for CMV infection.MethodsAll adult patients with seropositive CMV antibody admitted to a KT unit from January 2014 to December 2017 were retrospectively reviewed in a tertiary-care hospital in South Korea. Our hospital adopted preemptive ganciclovir therapy for CMV infection in all CMV seropositive KT recipients. We administered acyclovir prophylaxis for 1-month to CMV seropositive KT recipients. The primary endpoint was VZV infection development after KT.ResultsA total of 1295 KT recipients was followed up for 4295.8 person-years. The median follow-up period was 46.6 months (interquartile range (IQR) 34.3-59.5). Of the 1295 recipients, 100 (7.7%, 2.33 per 100 person-years, 95% confidence interval (CI) 1.89-2.83) patients developed VZV infection after KT. The median time for VZV infection development was 9.5 months (IQR 4.7-22.1). All patients had VZV-associated skin lesion, 9 postherpetic neuralgia, 2 visceral involvement and 3 disseminated infection. Of 100 patients, 16 patients need hospitalization due to VZV infection. In multivariate analysis, deceased donor KT (Hazard ratio (HR) 1.6; 95% CI 1.0-2.39, p = 0.05), mycophenolate maintenance immunosuppressive therapy (HR 0.3; 95% CI 0.14-0.75, p = 0.01) and rejection episode (HR 0.31; 95% CI 0.14-0.71, p = 0.01) were independently associated with VZV infection development after KT.ConclusionAbout one tenth of CMV seropositive KT recipients developed zoster after 1-month ACV prophylaxis during CMV preemptive strategy, especially in those who received deceased donor KT, mycophenolate therapy, and rejection episodes.Disclosures All Authors: No reported disclosures

O19 A Complex Case of Systemic Lupus Erythematosus with Class IV Lupus Nephritis in a 15-year-old Egyptian Girl

O19 A Complex Case of Systemic Lupus Erythematosus with Class IV Lupus Nephritis in a 15-year-old Egyptian Girl

Mycophenolate for the Treatment of Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Currently, there is an increasing trend toward non-steroid therapy for the treatment of autoimmune diseases. Some biological agents or immunosuppressive drugs may be the ideal choices. In real-world practice, as patients have severe systemic complications or organ damage, they will have a bad prognosis even if they are treated with high-dose steroids and strong immunosuppressive drugs. However, if we can start early intervention and prevent progressive development in advance, the patient may have a good prognosis. Mycophenolate is an immunosuppressive drug with minor side effects. Here, we conduct a systemic review and find supporting evidence that patients with pSS benefit from early mycophenolate therapy. Mycophenolate may be the first-line treatment for pSS patients in the future.

IS it mycophenolate induced colitis or flare-up of crohn’s disease? A diagnostic dilemma for histopathologists

Mycophenolic acid (MPA) is an immunosuppresive drug commonly used in patients with solid organ transplant. It inhibits the de novo pathway of purine synthesis that is crucial in cellular rejection of grafts. The same pathway is utilised by enterocytes for regeneration. MPA is a well-known cause of gastrointestinal mucosal injury which can take many forms and closely mimics other gastrointestinal diseases histologically including inflammatory bowel diseases, opportunistic infections and graft-versus-host disease. This case study reports a patient with a background history of Crohn’s disease and lung transplant who is on mycophenolate therapy, presenting with diarrhoea and abdominal pain. Endoscopy revealed large confluent ulcers and severe pancolitis. Infective aetiologies including opportunistic infections have been carefully excluded. Histologically, the colonic biopsies demonstrate patchy active chronic colitis with ulceration and focal cryptitis. Mild crypt architectural distortion and focal crypt atrophy are seen. Eosinophils are inconspicuous. All of the above features can be observed in both mycophenolate-induced colitis and Crohn’s colitis. This case report highlights the diagnostic dilemmas of histopathologists in this situation, followed by a review of latest literature and discussion on a meaningful differentiation of the two entities.

Treatment of primary sjögren's syndrome-related interstitial lung disease: a retrospective cohort study.

Background:Interstitial lung disease (ILD) is a common complication of primary Sjögren’s syndrome (pSS). Because there is a paucity of literature on the management of pSS-associated ILD (pSS-ILD), this retrospective cohort study assessed the efficacy of azathioprine and mycophenolate therapy in adult patients with pSS-ILD.Methods:A retrospective cohort study was performed using electronic health records to identify adults meeting the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for pSS. The presence of pSS-ILD was confirmed by characteristic high-resolution computed tomography and/or histopathology findings. Sociodemographic, clinical, and pulmonary function test (PFT) data were abstracted for patients meeting the criteria and followed longitudinally from the date of their ILD diagnosis. PFT values were anchored on time of treatment start, and linear mixed-effects modeling was used to analyze changes in diffusion capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) before and after treatment initiation.Results:We identified 19 subjects who had pSS-ILD, of whom seven were treated with azathioprine and seven were treated with mycophenolate. Within the azathioprine treated group, FVC% slope change trended toward improvement from a rate of -9.8% per month pre-treatment to 2.1% per month post-treatment (p = 0.13). Within the mycophenolate treated group, FVC% slope change improved from a rate of 1.5% per month pre-treatment to 4.3% per month post-treatment (p = 0.02) and DLCO% slope changed from a rate of -3.8% to –1.3% per month (p = 0.01) after therapy start.Conclusions:Mycophenolate treatment was associated with significant improvement in PFTs of pSS-ILD patients over time, and azathioprine treatment followed a similar non-significanttrend. Additional prospective studies are needed to further evaluate these findings. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 136-147)

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels.

Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P=0.003), INR<1.1 (P=0.02), and lower immunoglobulin gamma (IgG; P<0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P=0.07) or treatment indication (P=0.63). On multivariable analysis, lower pre-treatment serum IgG level (P=0.01), higher age at commencing mycophenolate (P=0.01) and higher INR (P=0.03) were the only significant independent predictors. An IgG level <17g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.

Longitudinal immunosuppression data can minimize misclassification bias in solid organ transplantation cohorts

Most cohort studies investigating the effect of immunosuppression on transplant outcomes use drugs at first hospital discharge. We evaluated the extent of drug exposure misclassification and its impact on outcome prediction. We retrospectively collected longitudinal immunosuppression data, at discharge and at 1, 5, 10, and 15years after transplantation, and outcomes for solid organ transplant recipients 1984-2006 (n=3133). We compared the risk of death from exposure to individual immunosuppressive drugs (cyclosporine, tacrolimus, azathioprine, and mycophenolate) and dual therapies, as defined by discharge only vs longitudinal immunosuppression data, using adjusted Cox proportional hazards models. During a median follow-up of 5.2years, immunosuppressive drugs were altered for 947 (30%) recipients and 955 recipients died. Longitudinal receipt of cyclosporine and azathioprine were associated with an increased risk (HR 1.41, 95% CI 1.07-1.89, and HR 1.34, 95% CI 1.00-1.80), and mycophenolate with a reduced risk (HR 0.35, 0.16-0.78), of death. Recipients on mycophenolate and tacrolimus dual therapy had a lower risk of death compared to those on azathioprine and cyclosporine dual therapy (HR 0.30, 0.10-0.93). The increased risk of death associated with the receipt of cyclosporine or azathioprine was not shown in the analyses based on drugs allocated at discharge, and all of the associations between immunosuppressive regimens and death were strengthened in the analyses based on longitudinal immunosuppression data. Cohort findings based on immunosuppressive drugs allocated at discharge should be interpreted with caution due to potential exposure misclassification. The use of granular, longitudinal data on immunosuppressive regimens could improve prediction.