Mg Of Daily Prednisone Research Articles

Children with autoimmune hepatitis receiving standard-of-care therapy demonstrate long-term obesity and linear growth delay

Background: Standard-of-care therapy in children with autoimmune hepatitis (AIH) includes induction with prednisone 1–2 mg/kg daily with gradual weaning of the dose. We aimed to test the hypothesis that children with AIH receiving standard-of-care treatment have altered growth trajectories. Methods: Children diagnosed with AIH between 1997 and 2023 at SickKids had serial growth measurements. Mixed effect models assessed the impact of time and daily steroid exposure on z-scores. Kaplan-Meier survival methods were used to estimate the cumulative incidence of new-onset growth impairments. A time-dependent Cox proportional hazards model was constructed to determine predictors for growth impairments. Results: Sixty-one children (66% females, median age at diagnosis 11.5 y) were included. BMIz showed a sharp increase, and HAZ declined significantly without returning to baseline. Each 1 mg/kg/d prednisone exposure increased BMIz gain in the first 6 months by 0.27 ([95% CI: 0.11, 0.42], p = 0.001), and decreased HAZ by −0.02 ([95% CI: −0.03, −0.01], p = 0.005). Children diagnosed before puberty exhibited a higher occurrence of excessive weight gain (72.2% vs. 49.3%; log-rank p < 0.01) and obesity (63% vs. 31.5%; log-rank p < 0.01) compared to those diagnosed during puberty. In a Cox proportional-hazards model, young age at diagnosis and daily prednisone dose >10 mg 6 months after diagnosis were predictors for linear growth delay. Conclusions: This study demonstrates that children with AIH receiving standard-of-care therapy demonstrate altered growth trajectories, long-term excess weight gain, obesity, and linear growth delay. Young age at diagnosis and >10 mg of daily prednisone at 6 months are predictors for linear growth delay. These data indicate the need to re-evaluate standard treatment algorithms for pediatric AIH in terms of steroid dosing and potential nonsteroid alternatives.

Comparison of Steroidogenic Exposure Following the Administration of Repository Corticotropin Injection With a Synthetic ACTH1‐24 Depot and Methylprednisolone in Healthy Subjects

The pharmacokinetics (PK) and pharmacodynamics (PD) of clinically relevant doses of repository corticotropin injection (Acthar Gel) and synthetic ACTH1‐24 depot have not been fully characterized. We compared the steroidogenic exposure of repository corticotropin injection and synthetic ACTH1‐24 depot in healthy adults at therapeutic doses using data from 2 separate phase 1 studies. Subjects were randomly assigned to repository corticotropin injection 40 or 80 IU subcutaneously twice weekly or 80 IU subcutaneously 3 times weekly for 15 days or to daily synthetic ACTH1‐24 depot doses of 0.5 mg subcutaneously, 0.75 mg subcutaneously, 1 mg subcutaneously, or 1 mg intramuscularly for 5 days. A population PK/PD model was developed to simulate the free cortisol exposure of a clinically relevant dose of synthetic ACTH1‐24 depot (1 mg subcutaneously twice weekly). Study drug doses were converted to methylprednisolone‐equivalent doses using the steroidogenic exposure of methylprednisolone 16 mg daily as a conversion factor. Doses were also converted to prednisone equivalents using a coefficient of 1.25. These analyses revealed that the steroidogenic exposure of repository corticotropin injection at clinically relevant doses was substantially lower than that for synthetic ACTH1‐24 depot. The 3 repository corticotropin injection regimens were equivalent to approximately 5, 8, and 16 mg of daily prednisone, respectively. On the basis of simulated free cortisol exposure, synthetic ACTH1‐24 depot 1 mg subcutaneously twice weekly was comparable to 57 mg of daily prednisone. These results suggest that repository corticotropin injection has pharmacological effects that cannot be considered identical to synthetic ACTH1‐24 depot.

A233 VEDOLIZUMAB FOR STEROID & INFLIXIMAB-REFRACTORY ICI-COLITIS

Abstract Background Immune checkpoint inhibitors (ICI), such as anti-PD1, improve survival in melanoma, renal carcinoma and prostate cancer. However, by disinhibiting the immune system, these treatments cause significant immune-related adverse events (irAE), including colitis. For ICI-colitis, guidelines suggest escalating from observation to steroids to infliximab, without strong evidence for additional options should these fail. Vedolizumab has been used in a small number of cases for steroid-refractory or dependent ICI-colitis; only 9 cases have been reported in patients who failed infliximab therapy with a response rate of 67%. Aims To discuss a case of ICI-colitis that failed multiple steroid courses and infliximab infusions, but achieved remission with vedolizumab. Methods A 65-year-old male with malignant melanoma was randomized to adjuvant nivolumab +/- ipilimumab and developed non-bloody diarrhea. Despite loperamide, diarrhea worsened to 4–5 bowel movements daily. Stool cultures and C. diff were negative and 85mg of daily prednisone was started, while the ICI was held for 8 weeks. After a 2nd steroid taper, diarrhea recurred and the patient received 2 infliximab infusions 18 days apart. Despite initial improvement, biopsies demonstrated colitis and he underwent a 3rd infusion with little response. Clinical and biopsy-confirmed remission was only achieved once 2 vedolizumab infusions were given. Results Colitis is the most common ICI irAE, ranging in severity from mild to perforation and death. The incidence of grade 3 and 4 colitis, which require ICI discontinuation, is 1.3% for anti-PD1 and 13.6% in combination therapy. The severity of irAE is positively correlated with malignancy response and stopping ICI risks recurrence. Those that fail irAE medical management may require surgery. Thus, there is an impetus to continue the ICI and provide effective medical management for irAE. ICI-colitis guidelines are based on the CTCAE diarrhea classification and suggest supportive management and ICI continuation for grade 1. For grade 2, the ICI is held and steroids are started; infliximab is added for grades 3 and 4. However, 33–66% of patients are steroid-refractory or dependent; and patients may be infliximab non-responders, or unable to tolerate systemic side effects. Vedolizumab, an anti-α4β7-integrin, acts locally to inhibit T cells in the bowel wall, reducing inflammation in IBD. Recent reports, including ours, suggest usefulness in steroid and infliximab-refractory ICI colitis after only 2–4 infusions. When the inflammatory burden is high, the response rate is >80% and given its gut-specificity, side effects are minimal compared to infliximab. Although further evaluation is required, using vedolizumab as second-line therapy is reasonable. Conclusions Given vedolizumab’s safety and gut-specificity, it should readily be considered in the treatment of ICI irAE. Funding Agencies None

A CASE OF ANAPHYLAXIS SECONDARY TO RESLIZUMAB

Introduction Reslizumab treats severe eosinophilic asthma in adults not controlled with medical therapy. This drug is a well-tolerated humanized IgG4 kappa monoclonal antibody binding to IL-5 to reduce eosinophils. We report a case of anaphylaxis secondary to reslizumab. Case Description A 71-year-old female with severe persistent corticosteroid-dependent asthma presented with reslizumab anaphylaxis. She had uncontrolled asthma despite 20-30 mg of daily prednisone, montelukast 10 mg qHS, budesonide/formoterol 160/4.5 mcg, and inhaled tiotropium 2.5 mcg. The patient had an absolute eosinophil count of 800. Reslizumab 234 mg monthly was started. After her first dose, she had increased exercise tolerance and weaned off prednisone. After her second injection, the patient failed to report transient urticaria and palpitations beginning 1 hour after reslizumab completion. She took 50 mg diphenhydramine, and symptoms resolved. With her third injection, the patient developed wheezing, urticaria, morbilliform rash, palpitations, and lip swelling 1 hour after completion. She was treated with epinephrine 0.3 mg, prednisone taper, twice daily famotidine 150 mg, and twice daily loratadine. Symptoms resolved, and reslizumab discontinued. Since then, the patient has tolerated benralizumab with no side effects. Discussion Reslizumab significantly reduces eosinophils and improves lung function (AQLQ score, FEV1) thereby improving asthma control and quality of life. The most commonly reported adverse effects include headache, upper respiratory tract infections, and nasopharyngitis. Reslizumab rarely has been associated with anaphylaxis (0.3%), and it is important to establish safety and efficacy. More information is needed for monitoring morbidity and mortality, as well as consequences of withdrawal of therapy.

FRI0143 Correlation between frax score and likelihood of adherence with current osteoporosis treatment guidelines among rheumatologists caring for patients with rheumatoid arthritis

BackgroundAdherence to osteoporosis (OP) treatment and prevention is not optimal in many patients. Those with rheumatoid arthritis (RA) have a higher risk of OP due to steroid use and systemic...

Two Systemic Lupus Erythematosus Patients With Severe Pleurisy: Similar Presentations, Different Causes

History of the present illness. A 25-year-old woman was diagnosed with systemic lupus erythematosus (SLE) 2 years prior to admission, after she presented with fever, malaise, lymphadenopathy, arthritis, myalgias, malar rash, and positive serologies for antinuclear antibody (ANA) and anti–double-stranded DNA (anti-dsDNA). Additional serology tests were negative for anti-Ro/SSA, anti-La/SSB, RNP, and Sm antibodies, as well as antiphospholipid antibodies (aPL). She was treated with intermittent courses of glucocorticoids (GC) for disease flares. Eight months before admission, she had a severe flare that manifested with high fevers, weight loss, delirium, spastic bladder, and non-nephrotic proteinuria. She was ultimately diagnosed with gray matter transverse myelitis of the conus medullaris and lupus nephritis. She was treated aggressively with pulse GC and intravenous (IV) cyclophosphamide (CYC), which led to resolution of all symptoms. After completion of a 6-month course of IV CYC, she was maintained on 20 mg of prednisone. One month prior to admission, she was admitted to another hospital with leftsided pleurisy, dyspnea, and high fever. A chest computed tomography (CT) scan excluded pulmonary embolism, but showed bilateral lung lower lobe consolidations with pleural effusions (left larger than right) and a small fluid collection adjacent to her spleen. Her blood cultures grew Salmonella. Her symptoms improved with cefepime and high-dose GC, and she was discharged home 2 weeks later on 60 mg of daily prednisone and oral levofloxacin for a total of 3 weeks of antibiotics. In addition, she was discharged on trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg 3 times weekly for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. One week before her current admission, she was started on 1,000 mg of mycophenolate mofetil (MMF) daily. She then presented to our hospital with acute left-sided pleuritic chest pain, dyspnea, and arthralgias. She did not have fever or cough.