Steroid Dose Research Articles

DIPG-42. PHASE 1/2 CLINICAL TRIAL OF OMBIPEPIMUT-S IN JAPANESE PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY DIFFUSE INTRINSIC PONTINE GLIOMA, GLIOBLASTOMA, OR HIGH-GRADE GLIOMA

Abstract BACKGROUND Pediatric patients with recurred/relapsed diffuse intrinsic pontine glioma (DIPG), glioblastoma, or high-grade gliomas (HGGs) have a dismal prognosis. The present study investigated the impacts of 1) the absolute count of Wilms tumor 1 (WT1)-specific cytotoxic T cells (CTLs) at the initiation of WT-1 specific peptide vaccine (Ombipepimut-S) consisting of a killer peptide—adegramotide, a helper peptide—nelatimotide, and adjuvant MontanideTM ISA 51 VG and of 2) cumulative steroid dose on patients’ survival. We aimed to explore the optimal timing for initiating this cancer immunotherapy for them. METHODS The absolute counts of WT1-specific CTLs and lymphocytes were examined at the initiation of vaccination. This first-in-child phase 1/2 study investigated survival (overall survival [OS] and progression-free survival [PFS]), as well as cumulative steroid dose until day 28 after vaccination initiation and immune responses according to the Kaplan-Meier method and receiver-operating curve (ROC) analysis, respectively. RESULTS 18 patients (median age: 8.9 years [range: 2.8–18.7]), 11 (61.1%), 5 (27.8%), and 2 (11.1%) had DIPG, glioblastoma, and HGG, respectively) were intradermally injected with ombipepimut-S. WT1-specific immune responders accounted for 70.6% of patients. Median OS was significantly longer (P = 0.024) in WT1-specific immune responders (9.9 months [6.0−33.4]) than in nonresponders (4.9 months [2.2−16.5]). Under a low cumulative steroid dose (< 0.66 mg/kg body weight), ombipepimut-S significantly extended both OS (P=0.0015) and PFS (P=0.007). Immune responders tended to show the higher absolute counts of WT1-specific CTLs (P=0.091) and lymphocytes (P=0.087) at the initiation of vaccination. CONCLUSIONS Ombipepimut-S exhibited antitumor activity, and this cancer immunotherapy appeared to be preferably initiated when the patient’s immunity is relatively preserved immediately after the completion of standard therapy for primary disease or before the tumor recurs or relapses.

Impact of steroids indication on the efficacy of immunotherapy in a multi-tumor cohort of patients: Time and dose-dependent evaluation.

12083 Background: The detrimental impact of steroids (ST) on patients receiving immune checkpoint inhibitors (ICI) has been described in several studies. However, the influence of indication, time of administration, and dosage is more controversial. Methods: This is a retrospective analysis of 475 patients with advanced solid tumors treated with ICI at a tertiary university hospital, between 2015 and 2022. Data related to baseline characteristics and clinical outcomes were collected. For each patient, the daily ST dose (equivalent in mg/kg of prednisone) and indication were registered until progression or death. We evaluated the impact of ST indication on the objective response rate (ORR) and progression-free survival (PFS). In addition, we analyzed the potential influence of cumulative dose (CD) (patients were divided into quartiles (Q) based on the total dose of steroids received throughout ICI treatment) and time of administration (30 days from C1 (D1-30), 3 months from C1 (D1-D90) and after 6 months (m) from C1 (>6m)). Results: We analyzed 475 pts with advanced solid tumors (NSCLC: 33.9%; urothelial: 17.3%; renal: 13.7%; melanoma: 11.2%; head and neck: 11.0%; others: 12.9%) treated with ICI (anti-PD1 [64.4%], anti-PDL1 [20.4%], anti-PD1 plus anti-CTLA4 [13.3%] or anti-CTLA4 [1.9%]). 49.5% of pts received ST during ICI treatment (20.6% due to an immune-related adverse event [irAE] and 33.9% with other indications). 24.2% of patients received ST in D1-30 (5.7% irAE vs 20.6% other indications), 32.6% in D1-D90 (10.7% vs 25.1%) and 17.1% in >6m (12% vs 8%). The ORR was significantly higher in pts who received ST for irAES than in those treated with ST for other reasons both in D1-30 (40% vs 15.3%; p = 0.028) and in D1-90 (42.6% vs 17%; p = 0.001). Furthermore, the ORR was very similar to that of patients who did not receive any ST treatment (40% vs 37.8% in D1-30, and 42.6% vs 37.7% in D1-90). There was an inverse correlation between the CD of ST in D1-30 and the ORR (37.78% [no steroids], 29.63% [Q1], 21.42% [Q2], 11.11% [Q3] and 22.22% [Q4]). However, this association was not observed among patients receiving ST for irAEs during D1-30 (37.8% [no steroids], 100% [Q1], 0% [Q2], 33.3% [Q3] and 42.9% [Q4]; p = 0.21) and in D1-90 (37.7% [no steroids], 0% [Q1], 41.7% [Q2], 42.9% [Q3] and 52.9% [Q4]; p = 0.29). Finally, among patients without progression after 6 months from C1, PFS tended to be longer in those exposed to ST. However, PFS was similar regardless of the reason for ST use. Conclusions: Exposure to ST is associated with poorer ICI outcomes. Our study showed that the impact of ST is time- and dose-dependent. Interestingly, these results were not observed among patients exposed to ST due to irAEs, suggesting that immune toxicity may attenuate ST detrimental effects.

Real world tebentafusp-tebn experience at a tertiary care referral center.

e21526 Background: Tebentafusp-tebn is an FDA approved therapy specifically for patients with metastatic uveal melanoma (MUM). The major challenge of this treatment is the weekly infusion schedule and potentially significant toxicity during the dose escalation and induction phase (Cycle 1). To overcome this challenge, we developed a treatment model consisting of an induction phase at a tertiary center of MUM and subsequent treatments at a local cancer center. Methods: This retrospective cohort study included patients who received Cycle 1 at our institution since FDA approval. Patients who received initial induction doses at other health systems were excluded. Data was collected by chart review. Cytokine release syndrome (CRS) was graded by ASTCT consensus guidelines. Results: From 3/14/2022-11/7/23, 26 patients received at least one dose of tebentafusp-tebn at our institution. 14/26 were female and median age was 69 (range 51-80). 24/26 patients had metastatic disease to the liver, followed by bone (6/26), lung (3/26), and others (5/26). Patients underwent a median of 2 (range 0-5) lines of therapy prior to tebentafusp-tebn initiation. Major side effects during Cycle 1 included CRS (22/26), rash/itching (24/26), and nausea (3/26). One patient developed grade 4 liver enzyme elevations. Of the patients who developed CRS, 77.3% (17/22) were grade 1, 13.7% (3/22) were grade 2, and 9.1% (2/22) were grade 3. 5/26 (19.2%) patients required at least one dose of steroid for management of CRS. The median number of hospitalizations for Cycle 1 was 3 (range 3-6). After Cycle 1, 21/26 (80.8%) patients were successfully transitioned to local health systems to continue outpatient weekly tebentafusp-tebn infusions, including 2 patients who went were able to continue of therapy in their home countries. 1 patient is in the process of transferring, 1 patient discontinued after dose escalation due to disease progression, and 3 patients decided to continue treatment at our institution. 19 patients who were transitioned to their local cancer centers in the US traveled a median of 107 miles (range 30-298 miles) for Cycle 1 at our institution, and a median of 23 miles (range 4-58 miles) after transition to local health systems. The median number of days patients received therapy was 203 days (range 22-610 days). Median time to progression was 12.6 weeks (range 5.8-65.6). 6/26 (23.1%) patients have received additional therapy upon progression while continuing tebentafusp-tebn. 12/26 patients are currently receiving therapy and 2 patients were lost to follow up after transferring to a local site. At time of review 19/26 patients were alive. Conclusions: This hybrid model of treatment (Cycle 1 at a tertiary center followed by continuation at a local cancer center) made weekly tebentafusp-tebn treatment safe and feasible for patients with MUM. Our single center experience demonstrates side effects and outcomes similar to what has been reported in the clinical trial.

Daily compared with alternate-day levamisole in pediatric nephrotic syndrome: an open-label randomized controlled study.

Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2-3mg/kg/dose) for 12months. Prednisolone was tapered off by 3months. Patients were monitored for relapses, further steroid requirement, and adverse effects. A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects.

Ultra-low-dose rituximab is effective for the treatment of patients with minimal change disease - A retrospective study

Background purposeRituximab (RTX),an anti-CD20 monoclonal antibody can effectively treat minimal change disease (MCD),with low toxicity and a reduced steroid dosage. The optimal dosage of RTX for treating MCD remains unclear. This study aimed to investigate the efficacy of an ultra-low-dose regimen of RTX (100 mg per week for 4 weeks) for treating MCD. MethodsWe retrospectively analyzed clinical data from 31 patients with MCD who received RTX. Seventeen patients received ultra-low-dose RTX (ULD-RTX) therapy, and 14 patients received standard-dose RTX (SD-RTX) therapy (500 mg weekly for 4 weeks). All patients were followed up for at least 6 months. ResultsBoth groups showed significant increases in the serum albumin levels and notable decreases in the urinary protein levels in the 1st and 6th months after RTX therapy. There were no significant differences in the plasma albumin or urinary protein levels between the groups (p > 0.05). B-cell depletion was observed in all patients after 1 month of RTX administration. At 6 months after RTX treatment, the remission rate was 93% in the SD-RTX group and 88% in the ULD-RTX group (p > 0.05). The ULD-RTX therapy incurred lower costs than did the SD-RTX therapy. One patient in the SD-RTX group developed community-acquired pneumonia. ConclusionUltra-low-dose RTX is effective at inducing remission in patients with MCD at a lower cost.

Early combination with mycophenolate mofetil for immune-related hepatitis in patients with solid tumors treated with immune checkpoint inhibitors.

12133 Background: Hepatitis, as an immune-related adverse event (irAE), occurs in 2%-10% of patients treated with immune checkpoint inhibitors (ICIs). Although guidelines recommend the use of mycophenolate mofetil (MMF) for steroid-refractory and steroid-resistant ir-hepatitis, there has been no evidence on the efficacy of MMF. Methods: We retrospectively reviewed consecutive patients with solid tumors who developed grade 2 or higher ir-hepatitis requiring systemic steroids after ICIs (nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab and ipilimumab) between January 2015 and August 2023. The changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin level, according to the CTCAE version 5.0, were used to assess ir-hepatitis. ALT improvement was calculated as the ratio of the change in ALT values from onset to day 7, normalized by the ALT values at onset. Results: Among 4405 patients treated with ICI during the study period, 130 patients (3%) developed grade 2 or higher ir-hepatitis requiring systemic steroids. The median age was 62 (range: 19-85) years-old, and 122 patients (94%) had an ECOG performance status (PS) 0/1. These patients included 67 (52%) with melanoma, 35 (27%) with lung cancer, 7 (5%) with esophageal cancer, and 21 (16%) with other cancers. Among 123 evaluable patients, 46 patients (46/123, 37%) received MMF including 20 patients experiencing steroid-refractory and 26 steroid-resistant. The median duration from the start of systemic steroids to MMF was 11 days (range: 0-113 days). Improvement of hepatitis to grade 1 with MMF was observed in 40 patients (40/46, 87%) with a median time of 18 (range: 3-176) days. Of the patients evaluated for the impact of the timing of MMF on the improvement of ir-hepatitis (n=38), ALT improvement at day 7 after ir-hepatitis onset in patients who initiated MMF within 3 days of ir-hepatitis onset (early combination group, n=8) was significantly higher compared with the patients who initiated MMF after 3 days of ir-hepatitis onset (late combination group, n=30) (72.3% vs. 41.7%, p=0.02). Additionally, among patients evaluable for systemic steroid dosage (n=45), the total systemic steroid dosage in patients in the early combination group (n=8) was significantly less than in the late combination group (n=37) (median: 2120mg vs 4005 mg, p=0.02). Conclusions: MMF was effective for both steroid-refractory and steroid -resistant ir-hepatitis. Early combination with MMF in addition to systemic steroids can lead to a more rapid improvement of ir-hepatitis compared to late combination with MMF consequently reducing the total systemic steroid dosage. [Table: see text]

Health-related quality of life (HRQoL) with tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) with brain, liver, adrenal, or bone metastases in the phase II VISION trial.

8575 Background: Tepotinib, a highly selective MET inhibitor, showed robust and durable activity in patients with METex14 skipping NSCLC in the VISION trial (NCT02864992) (1). Systemic and intracranial activity was seen in patients with brain metastases. Secondary endpoints in the overall population showed stability in overall HRQoL, dyspnea and chest pain, with clinically meaningful improvement in cough. We analyzed HRQoL in patients with brain, liver, adrenal or bone metastases. Methods: Eligible patients (including patients with brain metastases if asymptomatic or neurologically stable on a stable steroid dose) received oral tepotinib 500 mg (450 mg active moiety) once daily. HRQoL was assessed at baseline and during follow-up using the EORTC QLQ-C30 Global Health Score (GHS), EQ-5D-5L visual analog scale (VAS), and EORTC QLQ-LC13 cough, dyspnea, and chest pain scores. Subgroup analyses evaluated patients with brain, liver, adrenal or bone metastases at baseline per independent review (data cut-off: November 20, 2022). Mean change from baseline across all visits was evaluated by linear mixed model regression in patients with baseline and ≥1 post-baseline score. Results: Of 313 enrolled patients, change from baseline in HRQoL was evaluable in 52 patients with brain (16.6%), 56 with liver (17.9%), 54 with adrenal (17.3%), and 86 with bone metastases (27.5%). At baseline, mean ± standard error (SE) EORTC QLQ-C30 GHS was worst in patients with bone metastases (49.90 ± 2.03), followed by patients with adrenal (51.85 ± 2.51), liver (58.33 ± 2.77), or brain metastases (59.94 ± 2.53). A similar pattern was observed for baseline EQ-5D-5L VAS (bone: 60.42 ± 1.94; adrenal: 63.06 ± 2.45; liver: 65.30 ± 2.46; brain: 66.75 ± 2.57). During tepotinib treatment, overall HRQoL (i.e. EORTC QLQ-C30 GHS and EQ-5D-5L VAS) remained stable in patients with brain, liver, adrenal or bone metastases (Table). Symptom scores in these patients showed trends for improvement in cough, with stability in dyspnea and chest pain. Conclusions: In the VISION trial in METex14 skipping NSCLC, patients with brain, liver, adrenal or bone metastases maintained overall HRQoL during tepotinib treatment, with trends for improvement in cough, consistent with results for the overall population. 1. Mazieres et al. JAMA Oncol 2023;9:1260–66. Clinical trial information: NCT02864992 . [Table: see text]

Evaluation of the frequency and risk factors of spontaneous intramuscular hemorrhage associated with dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myositis (IIM) characterized by skin manifestations and muscle involvement. Spontaneous intramuscular hemorrhage (SIH) is a fatal complication that is very rare in the course of DM, but not well known to rheumatologists. Our aim was to determine the frequency and possible risk factors of DM-related SIH. A retrospective analysis was conducted on a cohort of DM patients who were observed in the rheumatology department of the university hospital between 1998 and January 2024. The clinical, laboratory, radiological data of the patients and the treatments they received during the follow-up were analyzed. To determine possible risk factors for the development of SIH in the course of DM, our patients with DM were analyzed together with other rare SIH cases in the literature. The study included 42 of our DM patients. 32 of the patients (76.2%) were female. The median age of the patients was 53 (24–82) years, the median age of DM diagnosis of the patients was 47 (18–75) years, and the median duration of DM of the patients was 36 (2-276) months. 7.1% of patients had dysphagia, and 16.7% had intertitial lung disease (ILD). 5 (11.9%) patients were diagnosed with malignancy. The incidence rate of SIH development in our DM cohort was 0.238/100 patient years (95% CI 0.006–1.256). We tried to identify independent risk factors for SIH development by comparing our 41 DM patients without SIH with the data of patients with 23 DM-related SIH collected from the literature by adding our 1 patient (24 pts). Male sex (OR 4.97, 95% CI 1.66–14.92, p = 0.003), ILD presence (OR 9.71, 95% CI 2.99–31.47, p < 0.001), anti-MDA5 positivity (OR 16.0, 95% CI 1.60-159.3, p = 0.006), anti-Ro52 positivity (OR 11.6, 95% CI 2.93–46.34, p < 0.001), heparin use (OR 4.42, 95% CI 2.68–7.24, p < 0.001), intravenous immunoglobulin (IVIG) use (OR 11.7, 95% CI 2.26–60.54, p < 0.001), and steroid dose (OR 1.03, 95% CI 1.00-1.05, p = 0.005) were identified as risk factors for the development of SIH in the univariate analysis. The death rate due to hemorrhage was 50%. No single risk factor was found to be associated with death. As a result, SIH may occasionally arise in patients with DM. Rheumatologists should be aware that patients with dysphagia and/or ILD, who are on heparin, getting high doses of steroids, and test positive for anti-MDA5 and/or anti-Ro52 antibodies may develop SIH in the early stages of DM.

P.053 Concomitant corticosteroid use in ravulizumab-treated adults with anti-AChR antibody-positive gMG: results from the CHAMPION MG open-label extension

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could receive ravulizumab in the open-label extension (OLE; NCT03920293); corticosteroid adjustments were permitted. Methods: Patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg at Week 28 and every 8 weeks thereafter) for ≤4 years. Results: Among 161 patients (78 ravulizumab, 83 placebo) who entered the OLE and received ravulizumab for ≤164 weeks, 113 received oral or enteral corticosteroids during the OLE; the proportion treated with &gt;10 mg/day corticosteroids decreased from 58% (n=66) at first OLE dose to 37% (n=42) (35 [31%] received ≤5 mg/day and 71 [63%] received ≤10 mg/day) at last reported dose. Fourteen patients (12%) discontinued corticosteroids. The mean (SD) corticosteroid dosage/patient decreased from 17.5 (11.9) mg/day at first OLE dose to 11.7 (10.9) mg/day at last assessment. Conclusions: Ravulizumab decreased corticosteroid use in patients with AChRAb+ gMG, suggesting a steroid-sparing role for ravulizumab.

#567 Early application of treatment to patients with IgA nephropathy who were supposed to have steroid regimen predicts good renal outcome

Abstract Background and Aims Progressive deterioration of proteinuria and glomerular filtration rate (GFR) is notified in 20-30% of patients with IgA nephropathy during 20-30 years follow-up period. Popular traditional approach for patients with rapid deterioration of renal function is the immunosuppressive treatment with steroid, which efficacy is still remained in debate. We searched the factors related to renal outcomes among patients presumed to need steroid treatment. Method Among 472 adult patients with IgA nephropathy diagnosed by renal biopsy during 2003-2017 in a tertiary hospital, we selected 86 patients with initiation of steroid treatment for more than 1 months and with dose of more than 1000 mg of prednisolone after renal biopsy. We excluded patients with steroid treatment started one month or more before renal biopsy. The renal outcome was defined as decrease of GFR more than 50% from GFR at renal biopsy, decrease of GFR to less than 15 ml/min/1.73 m2, or a status to need renal replacement therapy during follow-up period after renal biopsy. Results At admission for renal biopsy, estimated GFR by CKD-EPI 2009 equation was 68.5 ± 33.3 ml/min/1.73 m2 and urine protein to creatinine ratio (UPCR) was 2.81 ± 2.23 g/g creatinine (no missing data). The renin-angiotensin-aldosterone inhibitor was used in 80 patients (93.0 %) after renal biopsy. Steroid was started at 8.4 ± 23.1 months after renal biopsy. Majority of patients (63 patients) had been prescribed steroid medication within 2 months after renal biopsy. Total dose of steroid was 13.5 ± 13.1 g. The results of eGFR and UPCR before starting steroid medication were 63.7 ± 31.2 ml/min/1.73 m2 and 2.82 ± 2.01 g/g creatinine, respectively. During 63.6 ± 48.8 months of follow-up period after renal biopsy, there were 39 patients (45.3 %) developed the renal outcome. Factors related to development of the renal outcome searched by correlation coefficient were eGFR and UPCR at renal biopsy, medications of anti-diabetic agent, anti-hypertensive agent, immunosuppressive agent other than steroid, dose of steroid, or vitamin D3 agent after renal biopsy, pathologic findings of segmental sclerosis, interstitial inflammation, and tubular atrophy on light microscopic examination, deposition of C3 and IgA on immunofluorescent staining, and Oxford classification of T, period of starting steroid treatment after renal biopsy, and eGFR before starting steroid medication. With Cox's hazard proportional model, the independent factors to predict the renal outcome were eGFR before steroid treatment or eGFR at renal biopsy, immunosuppressive medication other than steroid, pathologic finding of C3 deposition, and period of starting steroid treatment. Hazard ratio to estimate the renal outcome (HR) was 1.025 (95% CI: 1.010-1.039, p = 0.001) for one-month delay of starting steroid medication after renal biopsy. The HR for the renal outcome in patients started steroid medication at 2 months after renal biopsy was 2.353 (95% CI: 1.140-4.856, P = 0.021) compared to patients started steroid within 2 months after renal biopsy. Conclusion For the patients supposed to have indications for steroid treatment at renal biopsy, early initiation of steroid treatment would indicate better renal outcome.

#97 Study of association between post transplant diabetes mellitus (PTDM) and hypomagnesemia

Abstract Background and Aims New onset diabetes after transplantation (NODAT) or PTDM (Post-transplant Diabetes Mellitus) is associated with increased morbidity, renal graft loss, cardiovascular complications, mortality and increased health care costs. It has been shown that incidence of NODAT is rising in recent years. It is suggested that there is more prominent role of beta cell dysfunction rather than insulin resistance in patients with PTDM. Hypomagnesemia which is commonly seen in post-transplant patients is suggested to have a role in promoting beta cell dysfunction. Emerging modifiable risk factors for PTDM like hypomagnesemia need to be studied which may help to improve its prevalence and outcomes. Method This study was single centre study to assess association of PTDM or NODAT with hypomagnesemia. Other risk factors like body mass index (BMI) &amp;gt;25 kg/m2, higher age and sex of the recipient were also studied. This study was a prospective, non-randomised, comparative, observational study. Duration of the study was from 1st October 2016 to 28th February 2018. Recipients with age &amp;gt; 18 years with at least 2 fasting blood sugar readings of &amp;gt;126 mg/dl or 2 post prandial readings of &amp;gt;200 mg/dl or need for antidiabetic medications beyond 1-month post-transplant were studied as PTDM or NODAT. Patients with deceased donor transplant, second kidney transplant, simultaneous other organ transplant, active Hepatitis C infection, active cytomegalovirus infection, patients with acute rejection, patients with polycystic kidney disease and patients with basiliximab induction were excluded. Results After applying exclusion and exclusion criteria, 98 patients were studied in total. Among 98 patients around 40 patients developed PTDM. When assessed independently higher age of the patient (age more than 50 years) was associated with PTDM (p = .030) while sex of the recipient was not associated with PTDM (P = .188). BMI &amp;gt;25 kg/m2 was significantly associated with PTDM at 1 month (p = .0001), 2 month (p &amp;lt; .0001), 3 month (p &amp;lt; .0001), 6 month (p &amp;lt; .0001), 9 month (p = .0001) and 12 month (p = .003) post-transplant. No statistical difference between doses of steroids were seen in patients with or without PTDM. All 98 patients received tacrolimus as part of their immunosuppressant regime. Time varying serum tacrolimus trough levels were not associated with PTDM and was removed as confounder by using univariate cox proportional hazard model (p = 0.691). After univariate and subsequently multivariate logistic regression analysis only hypomagnesemia was significantly associated with PTDM (p = .0001). After using univariate and subsequently multivariate cox proportional hazard model to study time varying risk factors, both hypomagnesemia (HR, 0.099; 95% CI, 0.016-0.624, p = .014) and BMI &amp;gt;25 kg/m2 (HR, 3.435; 95% CI, 1.657-7.119, p = .001) were associated with PTDM. Significantly a greater number of patients with lower magnesium levels developed PTDM early as compared to patients with normal magnesium levels (Spearman's coefficient of rank correlation (rho) = 0.53; 95% CI, 0.261-0.722, p = .0004). Conclusion Hypomagnesemia and overweight are modifiable risk factors significantly associated with PTDM even after removing confounding factors. Early development of PTDM in patient with hypomagnesemia further corroborates its role. Active interventions should be sought to control hypomagnesemia and overweight which may improve the morbidity and mortality of kidney transplant patients in long run.

#3140 Investigating the impact of Anti-IL5 therapy in eosinophilic granulomatosis with polyangiitis (EGPA): a three year longitudinal perspective

Abstract Background and Aims In the randomized, placebo-controlled MIRRA trial [1] for relapsing and refractory eosinophilic granulomatosis with polyangiitis (EGPA), adjuvant therapy with 300 mg anti-IL5 mAB Mepolizumab [MEPO] for 12 months (M), accrued longer times in remission, reduced steroid exposure and reduced relapse rates [1]. The aim of this study is to analyze the outcome of 100 mg MEPO monthly s/c for a minimum of 36 months. Changes to adjuvant immunosuppression and indications for anti-IL5 class switch from MEPO 100 mg s/c to Benralizumab (BRZ) or Reslizumab (Res) were assessed. Method In this observational study, 20 EGPA patients received anti-IL5 therapy for a minimum of 36M (range 49-68M). All commenced on 100 mg s/c MEPO every four weeks. Anti-IL5 therapy switched to BRZ or Res due to partial response or intolerance. Assessment time points included MEPO commencement, 6, 12, 18, 24 and 36 months. Results Overall, there was a 50% reduction in steroid dose by 12 months. This continued to reduce to 24M, by which time 2 were off steroids and a further 10/20 (50%) on weaning dose ≤ prednisolone 5 mg/day. Mean steroid dose continued to decrease to 36 months. The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10/20 (50%) at M0 to 4/20 (20%) by M24. Clinical benefits included ANCA serology normalized in all four positive patients by 12 months. Mean eosinophil count reduced from 0.42 mg ± 0.33 × 109/L at M0 to 0.04 ± 0.03 × 109/L at 12 and 24M. BVAS reduced from median 5 [3-7], to 0 [0-1] by 24M. The change in mean FEV1 over 12 months was from (M0) 2.11 ± 0.66 to (M12) 2.39 ± 0.62 and FVC (M0) 3.42 ± 0.87 to (M12) 3.67 ± 0.93/105.60 ± 20.47 respectively. All 20 EGPA patients receiving anti -IL5 therapy, ranging from 49-68M remain on therapy. At 36M, 9 have remained on 100 mg s/c MEPO. 10 (50%) have switched to an alternative anti-IL5 agent—10 switched to benralizumab, 1 initially on benralizumab to reslizumab. 9/10 had achieved partial response prior to switch (reduction in steroids / relapse rate), 1/10 had no response.. During the duration of the study, 3 patients had a break of therapy, but all resumed anti-IL5 treatment with good response. Hence, all 20 remain on anti-IL5 beyond 24M. After 36M, one patient required cyclophosphamide along with anti-IL5 therapy for myocarditis. A further patient had Rituximab for EGPA/ Rheumatoid arthritis overlap between anti-IL5 agents. Conclusion In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 36M. By 24 months 2 are steroid free and a further 10 on weaning dose ≤5 mg. Furthermore, the number on adjuvant conventional immunosuppression reduced over the 24M (n = 4 at 24M). This study demonstrates that anti-IL5 therapy serves as a favorable model for steroid and conventional immunosuppressant minimization in EGPA. Clinical benefits of reduction in BVAS, improved pulmonary function tests and reduced serum eosinophilia were recorded. The relapsing nature of EGPA places a dependency of therapy on steroids and this study demonstrated sustained and ongoing improvement annually with continued anti-IL5 therapy. Some participants required a switch in anti-IL5 agent.

#2101 Beyond corticosteroids: rituximab in managing minimal change disease and glucocorticoid-related toxicity

Abstract Background and Aims Minimal Change Disease (MCD) is the primary cause of Nephrotic Syndrome in children, accounting for 10 to 20% of cases in adults. Glucocorticoids (GC) remain the cornerstone of treatment. Despite a positive response in the majority of patients, up to 25% experience frequent relapses, and up to 30% are GC-dependent, exposing them to significant GC-related toxicity. Rituximab has been increasingly used in these patients, although 2021 KDIGO guidelines still points to cyclophosphamide as the preferred second-line therapy. This study aims to describe a single-centre experience with RTX, examining its effectiveness and assessing its potential to reduce GC exposure. Method A retrospective cohort study was conducted on 19 patients with MCD who were considered for RTX at adult age at a tertiary hospital centre between 2015 and 2023. Patients who refused treatment, those with MCD associated with other glomerular diseases, and those with less than 6 months of follow-up post-RTX were excluded from the study. Results Twelve patients met the inclusion criteria, including 5 diagnosed before the age of 18. The mean age at RTX initiation was 38.8 ± 14.8 years, with 75% being male. The median MCD duration pre-RTX was 140.5 [18.8–353.5] months, and the median follow-up post-RTX was 18.0 [12.5–41] months. All patients had preserved renal function and exhibited GC-dependency and/or frequent relapses, with 8 patients having received prior cyclophosphamide and/or cyclosporine A (CsA) treatment. At RTX initiation, all patients were on GC therapy (median 11.1 [10–50] mg/day), with 4 also on CsA. 10 patients were in complete remission, while 2 were in a relapse phase, subsequently achieving complete remission. Various induction regimens were employed: 6 patients received 1000 mg of RTX twice within 2 weeks, 1 received a single dose of 1000 mg, and 5 received a single dose of 500 mg. Out of the 12 patients, 5 did not receive RTX maintenance administrations, while 6 received 500 mg of RTX every 6 to 9 months and 1 patient received 1000 mg every 6 months. Only one adverse event was reported, one uncomplicated upper respiratory tract infection. Regardless of the induction regimen, all patients maintained a sustained response with complete remission for the following 6 months. All the 7 patients who underwent RTX maintenance did not experience disease relapse, although 2 continued GC therapy (one due to an associated autoimmune disease). Among the 5 patients who did not undergo RTX maintenance, 3 maintained complete remission throughout the follow-up, with a mean time free from any immunosuppression of 14.8 ± 10.6 months. The other 2 patients relapsed at a mean time of 27.5 ± 0.7 months. After relapse, 1 patient resumed GC therapy, and both started RTX maintenance with 500 mg every 6 to 9 months, subsequently achieving and maintaining complete remission. Among the 12 patients, 9 discontinued GC (1 continued CsA) after an average of 5.9 ± 4.2 months post-RTX, with a mean GC-free period of 16.6 ± 13.2 months during the follow-up period. Conclusion RTX proved to be safe and effective for steroid-dependent and/or frequently relapsing MCD, even with a low induction single dose of 500 mg. This low induction regimen may be an effective and potentially preferable option to minimize toxicity. RTX can significantly reduce relapse rate and steroid dose, avoiding complications associated with extended and high-dose GC administration. Notably, this outcome was not achieved previously with cyclophosphamide or CsA. RTX maintenance therapy may not be universally required for all patients with MCD, since a long period without relapse can be observed after induction therapy. Considering the current absence of a marker for disease activity, it should be taken into account individual patient characteristics and disease severity, particularly previous relapses after RTX induction. Considering the RTX effectiveness, ability to extend remission, safety, and GC sparing ability, it should be seriously considered as the preferred second-line treatment.

#1602 Lupus nephritis multidisciplinary consultation: a new strategy for increasingly complex patients

Abstract Background and Aims Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. Recent management advances require greater collaboration between specialists and individualized treatments in severe cases. Method We conducted a retrospective, single-center study of a cohort of incident patients which were diagnosed with LN between 2015 and 2022 and began follow-up in the multidisciplinary rheumatology and nephrology consultation of our institution. Clinical and analytical characteristics at diagnosis and during follow-up were studied. The primary endpoint was complete remission rate at follow-up end, according to GLOSEN (Grupo de Estudio de Enfermedades Glomerulares de la SEN) [1] criteria. Changes in immunosuppression schemes over time were studied. Results 26 patients (92.3% women) were included. Median age at SLE diagnosis was 30.5 years [Interquartile range (IQR) 23.7 – 44.2]. Most patients were Hispanic (14 patients, 53.8%). Median time between SLE and LN diagnosis was 21 months (IQR 0-129 months). In 9 patients (34.6%), SLE and LN onset happened simultaneously. Most common renal manifestation was hematuria, which appeared in 19 patients (73.1%). Median proteinuria was 1.83 g/d (IQR 0.88-2.92) and serum creatinine level, 0.69 (IQR 0.51-1.18). Hypocomplementemia (88.5%) and positivity to anti-DNA (69.2%) were common. Most frequent classes found in renal biopsies were IV (30.8%) and V (23.1%). At LN debut, SLEDAI score, which assesses SLE manifestations, had a median value of 16 (IQR 12-20). Mycophenolate mofetil (96.2%) was the main induction agent. Intravenous steroids were administered in 14 patients (53.8%) and the rest received steroids at a dose of 0.5 mg/kg/day. Addition of another therapy, mainly tacrolimus (6 patients, 23.1%) and belimumab (4 patients, 15.4%), was needed to achieve remission in 12 patients (46.2%). In 8 of them (66.6%), treatments were added within the first 6 months. These 12 patients had less chronicity in the biopsy (median chronicity index: 0 vs. 2; p 0.004) and had higher proteinuria (median 1.41 g/day vs. 0.4 g/day; p 0.001). Likewise, SLEDAI score at 3 months was significantly higher in these 12 patients than in the standard of care group (median SLEDAI score 13 vs. 8; p 0.016). No differences were found in 3 month serum creatinine (p 0.181) or 3 month hematuria (p 0.496) After a median follow-up of 47 months, 15 (57.7%) and 9 patients (34.6%) achieved complete and partial remission, respectively. No differences in percentages of remission were observed between the 2 groups. Steroids were withdrawn in 12 patients (46.2%). Median steroid dose at the end of follow-up was 5 mg (IQR 3-5). Conclusion In our LN cohort, higher SLEDAI and proteinuria indicated the need for an individualized approach. Collaboration between Rheumatology and Nephrology specialists is essential to identify patients with these needs.

#2475 Glomerulonephritis associated with anti -TNF-α therapy

Abstract Background and Aims Biologic agents like tumor necrosis factor α inhibitors/ anti-TNF-α/, IL6 and CD80/26 are widely used in many rheumatologic diseases but these may also elicit effects on renal function. These drugs, as well as rheumatic diseases themselves, can cause autoimmune renal disorders. Though effective on the main inflammatory process the incidence of kidney injury associated with their administration is increasing. Various forms of glomerulopathies have been described in connection with biological therapy - proliferative lupus nephritis, oligo immune necrotizing crescentic glomerulonephritis, membranous glomerulonephritis, IgA nephropathy and others. Method We report the clinical and pathologic findings in two patients with Rheumatoid arthritis and Ankylosing spondylitis on biologic therapy with an anti-TNF-α agent. During the treatment they presented with nephritic syndrome requiring kidney histology. Results Case 1: The first patient is a 52-year-old man diagnosed with ankylosing spondylitis, HLA-B27 positive, 15 years before admission. Four years before admission treatment with Golimumab /anti-TNF-α/ has been initiated. During the follow-up period urine tests revealed proteinuria and hematuria, which required more detailed tests. The patient presented with clinical features of nephritic syndrome, marked lower extremity edema, hematuria, nephrotic range proteinuria, impaired hypertension control. Kidney biopsy revealed membranoproliferative glomerulonephritis. It was assumed that kidney injury was most likely associated with Golimumab therapy. Its administration was discontinued, and therapy was started with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Mycophenolate Mofetil 1500 mg was started from the third month. General condition and laboratory results improved considerably. The occurrence of stiffness and pain in the sacroiliac joints several months after stopping biologic treatment necessitated the inclusion of Sulfasalazine to the therapy. Initiation of therapy with another class of biologic agent, Anti-IL-17 monoclonal antibody, was discussed with the follow-up rheumatologists. Case 2: The second patient is a 66-year-old woman, with a history of hypertension and essential thrombocythemia, who was diagnosed with seropositive rheumatoid arthritis 3 years before admission, treated with Adalimumab /anti-TNF-α/. Follow-up examinations revealed low-grade proteinuria, hematuria and impaired renal function. Kidney biopsy revealed IgA nephropathy. Following the discontinuation of Adalimumab, the patient was treated with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Kidney function significantly improved at the third month of treatment and proteinuria was gradually reduced. Initiation of Rituximab /antiCD20/ treatment was discussed with rheumatologists. Conclusion Treatment with biological drugs can cause immune-mediated glomerular disorder/IGD/. These events are rare, and the causative effects of a specific drug is hard to establish. When a patient is suspected of having an IGD, kidney biopsy should be performed for the exact diagnosis. The drug should be discontinued, and the treatment for the new-onset renal disorder should be promptly started. A rechallenge test of the same or a similar drug should be avoided, whereas switching to a different therapy is a reasonable option.

#2623 Homeostatic Model Assessment (HOMA) in pediatric patients with nephrotic syndrome receiving tacrolimus

Abstract Background and Aims Children with nephrotic syndrome (NS) receive diabetogenic drugs like tacrolimus (TAC) and steroids. TAC is toxic to pancreatic β-cells and suppresses insulin production in a time and dose dependent manner. This is well documented in renal transplant patients who develop post-transplant diabetes mellitus (PTDM). Although overt diabetes is uncommon in children receiving TAC for NS, the subclinical effect on β cell function has not been studied. Our aim was to study pancreatic beta cell function as assessed by homeostasis model assessment (HOMA) indices in children with NS who received TAC therapy for at least 1 year duration. Method We performed a prospective descriptive study where we followed children (1-18 years) with NS who received TAC therapy for at least 1 year. We noted patient demographics, clinical and histologic pattern of NS, cumulative steroid dose (mg/kg/day) received 90 days prior and TAC C0 levels. Fasting insulin, blood sugar to calculate HOMA indices for IR (insulin resistance), HOMA % β for beta cell function, HOMA-IS (insulin sensitivity), C-peptide and HbA1C were done once at study inclusion and yearly intervals when required. Statistical analysis included Pearson's correlation, paired t test and regression analysis. Results We performed HOMA indices in 37 children (19 males, 18 females) between September 2021-February 2023. Six patients had 2 measurements during the study period. The mean age of onset of NS was 28 months (95% CI [20; 36]) and mean age at HOMA indices measurement was 69 months (95% CI [59; 79]). Of the 37 patients, 54% (20/37) had late steroid resistance, 32% (12/37) had early steroid resistance, 8% (3/37) had steroid dependent NS, 6% (2/37) had frequently relapsing NS. Kidney biopsy performed in 36 children showed minimal change disease in 55.5% (20/36) and focal segmental glomerulosclerosis in 44.5% (16/36). The mean TAC duration, TAC Co level and mean cumulative steroid dose received in last 90 days were 27 months (95% CI [22;32]), 4.54 ng/ml (95% CI [4.12;4.97]) and 0.36 mg/kg/d (95% CI [0.28;0.44]) respectively. Eleven (30%) patients had cutaneous signs of insulin resistance like acanthosis nigricans and 9 (24%) patients had fasting blood sugar of &amp;gt;100 mg/dl. In Pearson's correlation analysis we found positive correlation between TAC Co level, HOMA IR (r = 0.4, P = 0.008) and TAC Co, HOMA %β (r = 0.44, P = 0.003) and cumulative steroid dose, fasting blood glucose (r = 0.3, P = 0.46). There was negative correlation between TAC Co level, HOMA IS (r = −0.4, P = 0.007). In regression analysis, only TAC Co level significantly influenced all HOMA indices including insulin resistance, insulin sensitivity and beta cell function. A HbA1C of &amp;gt; 5.7 (pre-diabetes range) was found in 32.4% (12/37) patients which warrants further monitoring. C-peptide levels were significantly higher after 12 months of TAC therapy in 6 patients who had two measurements (p = 0.032). Conclusion Tacrolimus therapy for nephrotic syndrome in children can affect pancreatic beta cell function as assessed by HOMA indices. Long term monitoring of pancreatic beta cell function in children with NS on TAC is needed to assess the full extent of these subclinical alterations.

COVID-19 Associated Mucormycosis and Risk Factors: A Case-Control Study from Turkey

Background: Mucormycosis, a fatal fungal infection, has increased during the COVID-19 pandemic and posed significant challenges for clinicians. Objectives: Our research focused on identifying the clinical traits of patients with COVID-19-associated mucormycosis (CAM), comparing them with a control group, and identifying risk factors for the development of CAM. Methods: Our study was conducted on 39 CAM patients and 78 control patients from September 2020 to October 2022 at a tertiary education center and regional hospital. The control group was selected blindly in a 1:2 ratio among patients who did not develop mucormycosis, were hospitalized due to COVID-19, and were either discharged or deceased. The control group was matched to the case group regarding age and hospitalization date. To test potential risk factors for CAM, we performed a binary logistic regression analysis. The variables included in the multivariate binary logistic regression model were gender, diabetes, cumulative steroid dose (dexamethasone equivalent), duration of steroid treatment, and tocilizumab/anakinra treatment. Results: In our study, 39 patients were diagnosed with CAM. The average age of the patients was 66 ± 11.5 years. Of the patients, 54.7% (n = 64) were male, with a statistically significantly higher proportion of men in the CAM group (74.4% vs. 44.9%, P = 0.003). The diabetes rate was 51.3% (n = 60) among all patients, and it was higher in the CAM group (69.2% vs. 42.3%, P = 0.006). Regarding in-hospital mortality, the rate was higher in the CAM group (56.4% vs. 14.1%, P &lt; 0.001). The median length of stay in the hospital was 37 days for the CAM group and 10 days for the control group (P &lt; 0.001). The cumulative steroid dose was elevated in the CAM group compared to the control group (191 ± 61.4 mg vs. 117 ± 69.8 mg, P &lt; 0.001). The duration of steroid treatment was 16.5 ± 6.2 days in the CAM group, compared to 9.8 ± 4.7 days in the control group (P &lt; 0.001). Among CAM cases, paranasal involvement was the most common (56.4%), followed by rhino-orbital involvement (33.3%). In binary logistic regression analysis, male gender (OR, 3.9; 95% CI, 1.4 – 11.3), diabetes mellitus (OR, 4.4; 95% CI, 1.5 – 12.4), more than ten days of steroid use (OR, 5.5; 95% CI, 1.3 – 22.4), and tocilizumab/anakinra use (OR, 0.23; 95% CI, 0.06 – 0.8) were identified as risk factors for the development of CAM (p values 0.011, 0.005, 0.019, and 0.020, respectively). Conclusions: Male gender, diabetes mellitus, and steroid use for more than ten days were identified as positive risk factors, while tocilizumab/anakinra use was identified as a negative risk factor for the development of CAM.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study

PurposeRadiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. MethodsIn Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. ResultsResponse rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. ConclusionsThis Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Patients with Steroid Sensitive Nephrotic Syndrome: A Case Series

Nephrotic syndrome (NS) is one of the most common kidney diseases found in childhood. The prevalence of nephrotic syndrome worldwide is approximately 16 cases per 100,000 children with an incidence of two to seven per 100,000 children. Nephrotic syndrome may affect adults and children of both genders and any race. Nephrotic syndrome in children can be classified into three groups; secondary, congenital, infantile, and idiopathic. In first case, a 3-year-old male patient was presented with complaints of fever, cough for 6 days and swelling all over the body, decreased urine output, oral intake for 2 days, edema of face, body and tiredness for 3 days. Laboratory investigations showed elevated ESR, ferritin and lipid profile. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis conveyed right basal pleural effusion. In second case, a 4-year-old male patient was presented with complaints of facial puffiness, fever, breathing difficulty, abdominal distension and pain but no edema. He had history of right inguinal hernia and atrial septal defect. Cholesterol level was found to be elevated. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis showed mild ascites and right pleural effusion. Presenting third case, a 12-year-old female patient was presented with complaints of edema and decreased urine output. Patient had history of recurrent episodes of edema and decreased urine output for 11 months. Laboratory investigations showed elevated total cholesterol, declined LFT test and RFT test was found to be normal. Urine routine examination showed elevated urine albumin levels (+++), pus cells, RBC, granular cast and bacteria present. USG abdomen and pelvis indicate acute glomerulo nephritis and acute to moderate ascites. Here case series with 3 cases showed the sequence of nephrotic syndrome which is treated with corticosteroid with its side effects and cumulative dose of steroid in children. Keywords: Nephrotic syndrome, Hypocholesteremia, Hypoproteinuria, Hyponatremia, pediatric

Protocol for the systematic review of the Pneumocystis jirovecii-associated pneumonia in non-HIV immunocompromised patients.

Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy. Despite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine. The protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review of literature published between January 2010 and July 2023, using the databases PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies. It is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research. Here, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients.