Discontinuation Of Prednisone Research Articles

Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina. A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th-75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann-Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value <0.05 was considered statistically significant. One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65-77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10-15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3-20 on LEF versus 31.8 months, IQR 10-82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30-7.47, P = 0.011). This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.

Propensity Score Matching Analysis Comparing the Efficacy and Steroid Tapering Benefit of Extracorporeal Photopheresis to Best Available Therapy in Third-Line or Beyond Treatment for Chronic GvHD

Graft-versus host disease (GVHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). Although corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus-host disease (cGVHD), approximately one-half of cGVHD patients are refractory to corticosteroid therapy. The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photopheresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGVHD. Using propensity score matching (PSM), treatment outcomes were compared between ECP-treated patients (n=74) and a historical cohort of cGVHD patients treated with BAT (n=132). By adjusting for unbalanced risk factors between the groups, including GVHD severity at the start of therapy, acute GVHD history, and baseline corticosteroid dose, 62 patients were balanced and selected for PSM. In the PSM cohort, the ECP group showed a 12-month failure-free survival (FFS) rate of 70.1% versus 32.5% in the BAT group (P < .0001; hazard rate [HR], .214), and 93.1% 12 months' overall survival (OS) rate of 93.1% versus 68.1% in the BAT group (P=.0249; HR, .3811); multivariate analysis confirmed ECP's superior FFS and OS compared with BAT. Generalized linear model analysis showed faster tapering of corticosteroids and higher rates of prednisone discontinuation in the ECP versus BAT PSM groups in the first 6 months. The ECP group also had a higher percentage of prednisone discontinuation, by 6% at month 0, by 14.9% at month 3, and by 22.5% at month 6. The current study demonstrates superior FFS, OS, and steroid tapering efficacy for ECP compared with BAT as third-line therapy or beyond in cGVHD patients.

Abstract #1406508: A Rare Case of Calcitriol-mediated Hypercalcemia in a Patient with Pneumocystis Jiroveci Pneumonia and the Role of Steroids in its Management

Calcitriol-mediated hypercalcemia is an uncommon complication of Pneumocystis jiroveci pneumonia (PJP). Some cases of PJP have been reported in patients with solid organ transplants and AIDS. Here we present a case of calcitriol-mediated hypercalcemia due to granulomatous Pneumocystis jiroveci pneumonia in a patient with a history of multiple sclerosis. A 45-year-old man with a medical history of multiple sclerosis, spondyloarthritis, smoking, and bipolar disorder was admitted for the evaluation of fever, fatigue, constipation, confusion, and weight loss of 10 Lbs over three months. His medications include rituximab, methotrexate, vitamin D-4000 IU, lithium, and calcium carbonate-600 mg. Laboratory evaluation showed elevated serum calcium (15 mg/dl) with a suppressed parathyroid hormone (9 pg/mL). Other pertinent findings include mildly elevated 25-hydroxyvitamin D (87 ng/ml), significantly elevated 1,25-dihydroxyvitamin D (381 pg/ml), and normal PTHrP (<2 pmol/L), vitamin A (0.82 mg/L) and TSH (1.31 mU/L). Extensive workup including AFB smear for tuberculosis, ACE level for sarcoidosis, SPEP for multiple myeloma, leukemia-lymphoma flow cytometry, and CT chest and PET-CT for malignancy were unremarkable. Treatment with large-volume intravenous fluids, calcitonin, and zoledronic acid followed by denosumab showed a transient reduction in serum calcium level to 10.5 mg/dl in 2 days and a rebound to a peak of 15.4 mg/dl in a week. Bronchoscopy with bronchoalveolar lavage which was done for persistent fever and new onset hypoxia revealed PJP confirmed by PCR. With this new finding, the diagnosis of PJP-induced calcitriol-mediated hypercalcemia was considered. He was then treated with Bactrim and prednisone 60 mg daily. Due to the severity of hypercalcemia, he required a hemodialysis session while waiting for the medications to take effect. His calcium normalized a week after the initiation of steroids and antibiotics and he was discharged on a slow prednisone taper. Clinic follow-up 4 weeks after discharge showed normal calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels. Discontinuation of prednisone was attempted but resulted in rebound elevation of 1,25-dihydroxyvitamin D requiring continuation of low-dose prednisone 5 mg. Our immunocompromised patient developed hypercalcemia induced by PJP infection due to granulomatous production of 1α-hydroxylase resulting in increased calcitriol formation. Steroids unsurprisingly appear to have the best impact on PJP-induced hypercalcemia because of their anti-inflammatory property. In this clinical entity, it inhibits inflammation and granuloma formation leading to a reduction in the release of 1α-hydroxylase and 1,25-dihydroxyvitamin D levels. It is essential to consider PJP as an etiology of hypercalcemia, especially in immunosuppressed patients. Steroid appears to be effective medical therapy in this setting. The timing and duration of treatment, and the efficacy of bisphosphonates and denosumab, require further studies.

Effect of treatment with Fufang Huangqi decoction on dose reductions and discontinuation of pyridostigmine bromide tablets, prednisone, and tacrolimus in patients with type I or II myasthenia gravis.

To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type I and II myasthenia gravis (MG) through changes in the clinical symptom scores of 100 patients with type I and II MG. This study also aimed to examine dose reductions and dis-continuation of these 3 Western medicines after administration of Fufang Huangqi decoction. The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group (group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group (group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group (group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group (group D). The average treatment time was (15.6 ± 11.5) months (range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed. An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for (15.6 ± 11.5) months (range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after (4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after (8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after (5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after (19.8 ± 11.0) months; 76.92% reduced hormone dosage after (2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after (6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month; this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine. Fufang Huangqi decoction is effective for the treatment of type I and II MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.

Treatment Outcomes in Birdshot Chorioretinitis: Corticosteroid Sparing, Corticosteroid Discontinuation, Remission, and Relapse

To describe treatment-related outcomes among patients with birdshot chorioretinitis (BSCR). Retrospective cohort study. Patients diagnosed with BSCR at 2 tertiary care academic medical centers. Clinical and treatment-related data were collected for all patients with BSCR diagnosed between 2003 and 2017 at the 2 centers and for each eye at each clinical visit. Four outcomes were considered: (1) corticosteroid-sparing success, defined as inactive disease and prednisone dose of ≤7.5 mg/day; (2) corticosteroid-discontinuation success, defined as inactive disease and discontinuation of prednisone; (3) sustained drug-free remission, defined as inactive disease off all medications for ≥3 months; and (4) relapse of BSCR after remission. A total of 107 patients with BSCR were identified, of whom 94 had follow-up data. Corticosteroid-sparing success was achieved in 95.4% of the oral corticosteroid-treated patients at a rate of 0.60 successes per person-year (PY) (95% CI: 0.50/PY, 0.70/PY). The median time to corticosteroid-sparing success was 12 months. Corticosteroids were discontinued successfully in 76.5% of oral corticosteroid-treated patients (rate= 0.28/PY; 95% CI: 0.21/PY, 0.35/PY). The median time to successful corticosteroid discontinuation was 2.0 years. A sustained drug-free remission was achieved in 24 patients (rate= 0.06/PY; 95% CI: 0.04/PY, 0.09/PY), with approximately 25% of patients achieving remission by 4 years of follow-up. Relapse of inflammation in patients after achieving a sustained, drug-free remission occurred at a rate of 0.24/PY (95% CI: 0.14/PY, 0.37/PY). Successful corticosteroid sparing and discontinuation was achieved in the majority of patients with BSCR. Remission occurred less often, but data were limited by the time needed to induce a remission (4 years) and the amount of follow-up (median, 4.6 years). The relapse rate after a remission was 0.24/PY.

Remission and relapses of myasthenia gravis on long-term tacrolimus: a retrospective cross-sectional study of a Chinese cohort.

Objective:To identify the factors that predict the remission and relapses in myasthenia gravis (MG) patients improved by prednisone and tacrolimus treatment.Methods:A retrospective, observational cohort analysis of MG patients who achieved remission after receiving prednisone and tacrolimus were performed at Tongji Hospital. The main outcome measures were the time to remission, prednisone discontinuation, tacrolimus reduction–associated relapse, and treatment outcome.Results:After adding tacrolimus, 256 patients were able to achieve remission with a mean time to remission of 2.1 ± 1.4 months. After a median follow-up of 2.9 years, 167 patients (65.2%) discontinued prednisone, and 20 patients (7.8%) achieved complete stable remission. Moreover, 53 of the 109 patients who were tapering tacrolimus experienced relapses. In multivariable analysis, female sex, low tacrolimus concentrations, and quantitative myasthenia gravis (QMG) scores have a positive correlation with the time to remission; concomitant additional autoimmune disease (AID) and high anti-acetylcholine receptor antibody (AChR-ab) levels were significantly associated with low probabilities of prednisone discontinuation [odds ratio (OR) = 0.312–0.912, respectively]; rapid tacrolimus decrement speed (⩾0.76 mg/year) was an independent predictor for the development of relapse during tapering tacrolimus (OR = 5.662).Conclusion:Sex, tacrolimus concentrations, and QMG scores can be used as potential predictors of the time to remission in MG patients treated with tacrolimus and prednisone. Prednisone should be tapered slowly, especially in patients with additional AID or high serum titers of AChR-ab. To avoid symptoms recurrence, the dose of tacrolimus should reduce slowly, not exceeding 0.76 mg/year.

Propensity Score Matching Analysis Comparing Ruxolitinib Vs Historical Controls in 2 nd Line or Beyond Treatment for Chronic Gvhd after Therapy Failure

Propensity Score Matching Analysis Comparing Ruxolitinib Vs Historical Controls in 2 nd Line or Beyond Treatment for Chronic Gvhd after Therapy Failure

S2724 Clinical Presentation, Treatment Strategies, and Chronic Sequelae of Immune Checkpoint Inhibitor-Mediated Cholangiopathy: A Case Study

Introduction: Immunotherapy-mediated cholangiopathy (IMCp) is an under-recognized phenotype of immunotherapy-mediated hepatobiliary toxicity (IMH) with specific consequences. IMCp cases bear a risk of the need for treatment escalation beyond corticosteroids alone, and the long-term sequelae are not well documented. We describe a case of steroid-refractory IMCp successfully treated with tocilizumab and ursodiol. Case Description/Methods: A 56-year-old man, treated with ipilimumab and nivolumab for metastatic lung squamous cell carcinoma, presented with abnormal liver enzymes attributed to toxicity secondary to immune checkpoint inhibitors. The initial peak ALT was 273 U/L, with AST 128 U/L, alkaline phosphatase (ALP) 590 U/L, GGT 938 U/L, and total bilirubin 2.0 mg/dL; R factor was < 2, suggesting a cholestatic-predominant pattern of injury. Oral prednisone 60 mg/d and ursodiol yielded only partial improvement; prednisone dose was increased to 80 mg/d, and azathioprine (AZA) 50 mg/d was added. Liver biopsy confirmed histologic bile duct injury; abdominal MRI showed enhancement of the left, right, and common hepatic ducts. ALT increased to >350 U/L with total bilirubin to 2.4 mg/dL despite intravenous (IV) methylprednisolone 160 mg/d. IV tocilizumab (TCZ) 8 mg/kg was administered, allowing for tapering off of prednisone, while continuing ursodiol and AZA. ALT improved from 519 to 82 after 44 days, and another infusion of IV TCZ at 4 mg/kg was given. The ALT improved and remained stable in 40-50 range for another 5 months. The ALP approached a nadir of 160 and eventually settled between 300-400. After ursodiol and AZA were discontinued, brief increases were seen of ALT to 106, AST to 82, ALP to 574, and GGT to 1283, which improved to baseline after ursodiol was resumed. Nine months after initial diagnosis, MRI showed persistent intrahepatic biliary ductal dilation with normal common hepatic duct and common bile duct. Patient was doing clinically well. Discussion: In this case of relapsing and steroid-refractory IMCp, with intrahepatic sclerosing cholangitis, tocilizumab, an IL-6 receptor antagonist, yielded successful biochemical and clinical remission, allowing discontinuation of prednisone, despite persistent intrahepatic biliary dilatation. Ursodiol as an adjunct may also play a crucial role in treating IMCp to manage cholestasis and as maintenance therapy. Longitudinal studies are needed to determine if permanent biliary sequelae may occur and whether these features pose practical clinical consequences.Figure 1.: (A) Liver biopsy (H&E, 200x) histology demonstrating expansion of the portal tracts by inflammation which is centered on the damaged bile duct. (B) Abdominal MRI/MRCP showing enhancement of the intrahepatic biliary tree; some of the right intrahepatic ducts demonstrate new beaded appearance; related findings were interpreted as progressive when compared to a prior MRI/MRCP. (C) Chronological clinical course trending liver biochemistries in relation to treatments employed before and after development of immune checkpoint inhibitor-mediated cholangiopathy. (Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; Nivo, nivolumab; Pred, prednisone; UDCA, ursodeoxycholic acid or ursodiol; AZA, azathioprine; IV, intravenous; methylpred, methylprednisolone).

Gradual Glucocorticosteroid Withdrawal Is Safe in Clinically Quiescent Systemic Lupus Erythematosus.

ObjectivesPatients with systemic lupus erythematosus (SLE) are usually treated with glucocorticosteroids even during periods of clinically quiescent disease. A recent study showed that abrupt glucocorticoid withdrawal was associated with an increased likelihood of flare in the next 12 months. The aim of the present study was to assess clinical flare rates and damage accrual in patients who tapered glucocorticosteroids gradually.MethodsPatients from the Toronto Lupus Clinic with 2 consecutive years of clinically quiescent disease were retrieved from the database. Individuals who maintained a low prednisone dose (5 mg/day) comprised the maintenance group, whereas patients who gradually tapered prednisone within these two years comprised the withdrawal group. All individuals were followed for 2 years after prednisone discontinuation or the corresponding date for the maintenance group. Propensity score matching was implemented to adjust for certain baseline differences. Outcomes included clinical flares and damage accrual.ResultsOf 270 eligible patients, 204 were matched (102 in each group). Flare rate (any increase in clinical SLE Disease Activity Index 2000) was lower in the withdrawal group both at 12 (17.6% versus 29.4%; P = 0.023) and 24 months (33.3% versus 50%; P = 0.01). Moderate to severe flares (requiring systemic treatment escalation) were not different at 12 months (10.8% versus 13.7%; P = 0.467) but were less frequent at 24 months (14.7% versus 27.5%; P = 0.024). Damage accrual was less frequent in the withdrawal group (6.9% versus 17.6%; P = 0.022). No predictors for clinical flares were identified.ConclusionGradual glucocorticoid withdrawal is safe in clinically quiescent SLE and is associated with fewer clinical flares and less damage accrual at 24 months.

Favorable Outcomes Combining Vedolizumab With Other Biologics or Tofacitinib for Treatment of Inflammatory Bowel Disease.

Combining advanced therapies may improve outcomes in inflammatory bowel disease (IBD), but there are little data on the effectiveness and safety of this approach. We examined outcomes of patients who received vedolizumab in combination with another biologic or tofacitinib between 2016 and 2020. Fourteen patients (10 ulcerative colitis [UC], 3 Crohn disease, 1 indeterminate colitis) received a combination of advanced therapies. Vedolizumab was combined with tofacitinib in 9 patients, ustekinumab in 3, and adalimumab in 2. Median follow-up on combination therapy was 31 weeks. Normalization of C-reactive protein (CRP) or fecal calprotectin (<5 mg/L and <150 µg/g, respectively) was achieved in 56% (5/9) and 50% (4/8) of patients. Paired median CRP decreased from 14 mg/L to <5 mg/L with combination therapy (n = 9, P = 0.02), and paired median calprotectin from 594 µg/g to 113 µg/g (n = 8, P = 0.12). Among patients with UC, paired median Lichtiger score decreased from 9 to 3 (n = 7, P = 0.02). Prednisone discontinuation was achieved in 67% (4/6) of prednisone-dependent patients. There were 4 infections: 2 required hospitalization (rotavirus, Clostridium difficile), and 2 did not (pneumonia, sinusitis). During follow-up, 5/14 patients discontinued combination therapy (2 nonresponse; 1 improvement and de-escalation; 1 noninfectious adverse effect; 1 loss of coverage). In this retrospective case series of a cohort with refractory IBD, combining vedolizumab with other biologics or tofacitinib improved inflammatory markers, reduced clinical disease activity and steroid use, and was well tolerated.

Glucocorticoid discontinuation in patients with early rheumatoid and undifferentiated arthritis: a post-hoc analysis of the BeSt and IMPROVED studies

ObjectivesTo evaluate the success rate of glucocorticoid discontinuation and to study which factors are associated with successful discontinuation.MethodsData from two treat-to-target studies, BeSt (target Disease Activity Score (DAS) ≤2.4) and...

Calcitriol-Mediated Hypercalcemia from Hepatic Granulomatosis Following Percutaneous Cholecystostomy Tube

Granulomatous conditions can present with calcitriol-mediated hypercalcemia via increased 1-hydroxylase activity—activity that is not inhibited by calcium or calcitriol—indicating a lack of feedback inhibition. Differential diagnosis of granulomatosis is quite broad and can require extensive workup as highlighted by this case. Our patient is a 69-year-old white female admitted to the hospital with altered mental status and hypotension. Initial evaluation was concerning for infection, due to leukopenia and thrombocytopenia. CT abdomen revealed cholecystitis, percutaneous cholecystostomy tube was placed, and the patient’s mental status improved. One month after discharge, the patient presented to the hospital with a corrected calcium of 15.2 mg/dl. PTH was 22 pg/mL with normal renal function and phosphorus. The patient was treated with intravenous fluids, calcitonin, and zoledronic acid. Calcitriol was 69 pg/ml (18–75 pg/ml) and corrected calcium responded by time of discharge. During outpatient follow up, she was found to have corrected calcium 11.2 mg/dl and calcitriol 166 pg/ml with appropriately low PTH. Additional workup of apparent calcitriol-mediated hypercalcemia with whole-body CT imaging, tuberculosis screening, and flow cytometry only notable for possible right cervical lymphadenopathy on CT. Subsequent lymph node biopsy was benign. The patient completed a 30-day course of prednisone 20 mg daily followed by prednisone taper and her corrected calcium and calcitriol levels normalized. However, after discontinuation of prednisone, lab work demonstrated increase in calcium and liver enzymes. Repeat CT scan showed multiple hypoechoic areas with subsequent biopsy consistent with necrotizing hepatic granulomatosis. PAS-A, Fite, and AFB stains were negative for fungi and mycobacteria. Removal of cholecystostomy tube resulted in complete resolution of hypercalcemia and elevated calcitriol levels. Foreign body-induced granulomatosis is associated with PTH-independent hypercalcemia. Silicone has been implicated in foreign body granuloma. Hepatic granulomatosis is associated with percutaneous tube, especially with prolonged placement (approximately 11 months in this case). Removal of the foreign body is associated with improvement in hypercalcemia. Follow-up liver ultrasound demonstrated complete resolution of hepatic granulomas at three months following removal of the cholecystostomy tube.

Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound.

Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5mm, and CAV development was defined as MIT ≥1mm or an increase in MIT ≥0.5mm at year 1 compared with baseline or an increase in 0.3mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51±11years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5years is 41% in DA- vs. 59% in DA + (p=.012). Donor age was a strong predictor of DA (p=.016). Significant risk factors for CAV included male sex (HR=4.141, p=.001), non-Caucasian race (HR=1.98, p=.011), BMI<18kg/m2 (HR=4.596, p=.042), longer ischemic time (HR=1.374, p=.028), older donor age (HR=1.158, p=.009), and rejection with hemodynamic compromise within the first year (HR=2.858, p=.043). Prednisone discontinuation within 1year was associated with a lower risk of CAV (HR 0.58 p=.047). Initiation of proliferation signal inhibitors (PSI) within 2years resulted in fewer cases of CAV (HR 0.397 p<.001). In patients with an angiogram at 1year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

Evidence-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19

The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments.

Rapid discontinuation of prednisone in kidney transplant recipients from at-risk subgroups: an OPTN/SRTR analysis.

Although rapid discontinuation of prednisone (RDP) after kidney transplantation has been successful in low-risk recipients, there is concern about RDP use in recipients at increased risk for rejection or recurrent disease. Using SRTR, we compared outcomes for RDP versus maintenance prednisone-treated recipients for alladult 1st and 2nd transplants (n=169479) and the following 1st transplant subgroups: African American (AA); highly sensitized; those with a potentially recurrent disease; and pediatric recipients. For all adult 1st LD and DD transplants, RDP was associated with better patient and graft survival. For all LD subgroups, RDP and maintenance prednisone were associated with similar patient, graft, and death-censored (DC) graft survival. For 1st transplantDD subgroups, RDP was associated with better patient survival in AA, those with potentially recurrent disease, and pediatric recipients; graft survival with RDP was better in AAs. For adult 2nd DD transplants, RDP was associated with worse DC-graft survival. Importantly, for all differences, the effect size was small. With the exception of 2nd DD transplants, RDP protocols can be used without decreasing patient or graft survival for subgroups of 1st DD and LD kidney transplant recipients and for 2nd LD transplant recipients, at increased risk of rejection or recurrent disease.

Refractory adult-onset Still disease treated by tocilizumab combined with methotrexate: A STROBE-compliant article.

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ± 20.7 mg/day to 55.0 ± 11.1 mg/day after 2-week treatment, and to 3.3 ± 2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients’ conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.

Treatment of Active Cardiac Sarcoidosis with TNF Alpha Inhibitors

Background Cardiac sarcoidosis (CS) is associated with significant morbidity and mortality including progressive heart failure and sudden cardiac death. High-dose steroid immunosuppression remains standard of care for CS but there is a lack of randomized clinical trial data. As a result, there remains significant treatment variability among specialized centers. TNF alpha inhibitors are widely used for other inflammatory diseases and are generally well tolerated. However, little data, if any, exists regarding their utility in CS. TNF alpha inhibitors are particularly attractive given the potential adverse effects of chronic glucocorticoid based immunosuppression. The purpose of this study was to explore the effectiveness of TNF alpha inhibitors in active CS. Methods We performed a retrospective analysis of patients with metabolically active CS (defined by increased FDG avidity by cardiac PET imaging) who were treated with TNF alpha inhibitors. All patients underwent follow up PET imaging. Disease activity was quantified by the number of left ventricular (LV) myocardial segments with FDG avidity (based on a 17 segment model of the LV). Adverse events related to therapy was also recorded. Results Nine patients treated with TNF alpha inhibitors were included in this analysis. Eight Patients received the TNF alpha inhibitor, infliximab, one patient received adalimumab. Eight of the nine patients had previously received prednisone for CS; four transitioned from prednisone to infliximab due to adverse effects of steroid use; three transitioned because of continued active CS despite steroid therapy; one patient exhibited recurrent cardiac FDG avidity after prednisone discontinuation and another declined steroid treatment. The number of LV myocardial segments with active CS decreased from 8.6 +/- 3.6 to 1.9 +/- 3.5 (p=0.001) after a mean treatment duration of 7 months of infliximab that represents a decline of FDG avid LV segments by 72%. There was no significant change in LV ejection fraction (45 +/- 15% to 50 +/- 11% after therapy, p=NS). Six of the nine patients had complete resolution of active CS, and two had partial improvement. One patient experienced pancytopenia felt possibly related to infliximab; no other obvious adverse events were observed. Conclusions In this retrospective cohort, TNF alpha inhibition lead to significant improvement in disease activity based on FDG PET imaging. Most patients demonstrated complete resolution of active CS with minimal adverse effects. Further investigation into the use of TNF alpha inhibitors for treating active CS is warranted.

Effectiveness and tolerability of methotrexate in pulmonary sarcoidosis: A single center real-world study.

Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements. To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements. A retrospective study on pulmonary sarcoidosis patients receiving MTX therapy with various dose ≥3 months was conducted. The primary outcome was change in high-resolution computed tomography (HRCT) before and after MTX therapy. Other efficacy parameters included SGRQ score, prednisone dose change, discontinuation and relapse-free survival. Response-linked factors and safety outcomes were also analyzed. Overall, 49 patients (81.7%) were assessed as MTX responders by HRCT and there was no significant difference in clinical response rate among three groups with different doses. The health-related quality of life (HRQL) of the responders improved obviously, which was evidenced by SGRQ score declining from 16.7(IQR: 7.9-26.4) to 10.7(IQR: 4.8-19.3) (P=0.029). The corticosteroids sparing effect was confirmed in "responders" group (P<0.001). When MTX was discontinued in 11 responders with complete improvement, 2 patients experienced relapses within 15.5 (range: 1-30) months (mean follow-up time of these 11 responders: 13.5±13.0 months). No clinical characteristics were found related to MTX effectiveness. Adverse events occurred in 31.7% of the patients, with gastrointestinal-related being the commonest. Drug discontinuation owing to adverse events occupied 6.7% of the subjects. Nearly 80% of the sarcoidosis subjects had well response to MTX. Its effectiveness was irrelevant to the treatment dosages and baseline characteristics. A quite low relapse rate was witnessed in those complete responders discontinuing MTX therapies. The steroid-sparing effect, well drug tolerability and low drug withdrawal rate were observed in these patients even without folic acid supplements in clinical practice.

SUN-417 Recovery Of Central Adrenal Insufficiency In A Patient With Hypophysitis Secondary To Immune Checkpoint Inhibitors Therapy

Hypophysitis is a well-recognized immune-related adverse event that occurs in approximately 16% of patients treated with immune checkpoint inhibitors (ICIs), particularly the anti-cytotoxic T-lymphocyte associated antigen (CTLA4) monoclonal antibody, ipilimumab. While the synthesis and secretion of some anterior pituitary hormones may recover, central adrenal insufficiency is thought to be permanent. A 26-year old male with metastatic renal cell carcinoma was started on treatment with the anti-programmed cell death 1 (PD-1) monoclonal antibody nivolumab. His pre-treatment TSH was 3.27 (0.34-5.60 µIU/mL). Six weeks after his first dose of nivolumab he developed biochemical hyperthyroidism: TSH 0.04µIU/mL, FT4 2.1 (0.80-1.50 ng/dL), without symptoms. He continued treatment with nivolumab, and 11 weeks after the first dose he remained hyperthyroid (TSH undetectable, FT4 2.65 (0.80-1.50 ng/dL)). He was then started on ipilimumab in addition to nivolumab for 4 cycles. A baseline random serum cortisol drawn at 1:30pm was 15.0 (6.7 - 22.6 µg/dL). Five weeks after starting combined ICI therapy he developed sudden onset of severe fatigue, and reported feeling unable to get out of bed. Random serum cortisol was 2.0µg/dL at 1pm, and further pituitary hormone evaluation was performed: ACTH 16 (7.2-63.3 pg/mL), prolactin 47.2 (2.6-13.1ng/mL), LH 3.47 (1.2-8.6 mIU/mL), FSH 14.6 (1.3-19.3 mIU/mL), TSH 1.91, FT4 0.85, testosterone 545.46 (300-1080ng/dL). Thyroid autoantibodies (anti-TPO, thyroglobulin, TSH receptor) were normal. A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1mg/kg. A brain MRI reported no pituitary abnormalities. 48 hours after starting prednisone his symptoms resolved. He remained on prednisone 20mg daily for 4 weeks, and continued treatment with the ICI’s. His pituitary labs were repeated (3pm) - ACTH 5, cortisol 4.0, TSH 1.6, FT4 0.99, Testosterone 119, LH 3.63, FSH 18.4, IGF1 195 (155-432 ng/dL). His dose of prednisone was reduced to 5mg once daily. He continued to be monitored regularly by endocrinology with follow up testing of hormone levels. Four months after the initial presentation his testosterone level improved to 973.4, but his cortisol remained low. After five months his random serum cortisol (1pm) increased to 11.0, and testosterone was 901.5. The prednisone was cautiously discontinued with close monitoring for symptoms and hormone levels. He remained asymptomatic after discontinuation of prednisone, and after two months off glucocorticoid replacement his ACTH was 24.1 and cortisol was 13.0. This case demonstrates that central adrenal insufficiency can recover in patients who develop hypophysitis from ICI therapy. Close follow up and repeated measurement of pituitary hormones may identify more patients with hypothalamic-pituitary-adrenal axis recovery.

The Gift That Keeps on Giving? The Impact of Donor Coronary Atherosclerosis on the Development of Coronary Allograft Vasculopathy by IVUS

Purpose Cardiac allograft vasculopathy (CAV) is a leading cause of late graft loss . While there are numerous risk factors for the development of CAV, there is a paucity of data on the impact of donor derived atherosclerosis (DA), particularly as assessed by intravascular ultrasound (IVUS). Methods Retrospective single center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually upto 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥ 0.5 mm, CAV development was defined as MIT ≥ 1 mm or an increase in MIT ≥ 0.5 mm at year 1 or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using parametric hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation, proliferation signal inhibitors (PSI) initiation with CAV. Results Of 284 patients transplanted, 186 patients survived and had an IVUS at 1 year. Mean age of 51 ± 11 years, 70% male, 58% Caucasian with 27% supported by LVAD and 40% had DA. Patients who developed CAV at 1-year had longer ischemic times (4 vs. 3.7 hours, p=0.03), DA+ (65% vs. 39%, p=0.047) and older donor age (40 vs. 33 years, p=0.03). The 5-year cumulative incidence of CAV 41% in DA- vs. 59% in DA+ (Fig 1A). Significant risk factors for CAV were male sex HR 4.1, non-Caucasian race HR 2, underweight (BMI hemodynamic rejection within 1 year HR 2.9. Initiation of PSI within 2 years for reasons other than CAV resulted in fewer cases of CAV HR 0.40 p Conclusion In patients with a baseline and yearly IVUS, DA was more prevalent HR 2 in recipients who developed CAV. Reductions in CAV were seen in patients who discontinued prednisone in the first year or had early PSI initiation for reasons other than CAV. Early IVUS results may allow physicians to tailor immunosuppression and potentially delay progression of CAV.