Opioid Prescription for Sickle Cell Disease Misses Guideline Recommendation, With Ibrahim Gwarzo, MPH

 pain do not receive guideline-adherent opioid pain medication adequately, according to recent research from Nemours Children’s Health.

67th American Society of Hematology (ASH) Annual Meeting and Exposition

 in Orlando, Florida, by Ibrahim Gwarzo, DrPH, MPH, MBBS, a research scientist at Nemours Children’s Health, these data indicate an overall issue in opioid prescription during recurrent pain episodes, which are the leading cause of emergency department (ED) visits among patients with SCD.

The ASH has previously published guidelines for opioid dosage in patients with SCD; these emphasize the rapid initiation and frequent reassessment of tailored opioid dosing. Specifically, they indicated an ideal initiation time within 60 minutes of arriving in the ED. Additionally, in cases where second doses were necessary, the guidelines specify that they should be administered within 30 minutes of the first dose.

“There have been persistent reports of delays before receiving any form of pain intervention,” Gwarzo told 

 in an exclusive interview. “This is despite the clinical guidelines, which recommend swift evaluation and administration of pain medications for these patients.”

Gwarzo and colleagues analyzed de-identified electronic health records of patients from >200 health systems participating in EPIC’s Cosmos research platform. All ED visits with a primary International Classification of Diseases (ICD-10) diagnosis code indicating an SCD pain crisis where ≥1 opioid pain medication was administered were included. Those taking place before 2019 or after 2024 were excluded, along with visits with diagnosis codes of any SCD complication. The study’s primary outcome was the timeliness of ED opioid pain medication for acute, uncomplicated SCD pain, expressed as the percentage of guideline adherence for first and second opioid doses.

Investigators calculated guideline adherence as a percentage of overall visits where the first opioid dose was given within 60 minutes of arrival. For visits with multiple opioid doses, the second dose’s guideline adherence was calculated as the percentage of visits where the second dose was administered within 30 minutes of the first dose. Additionally, patient, visit, and facility factors were explored, including age, sex, type of healthcare setting, payer, and acuity level.

A total of 228 were included, with a total of 394,725 ED visits from 40,977 unique patients. The median age was 31 years (interquartile range [IQR] 24-38), and 55.2% of participants were female. Patients paid through public insurance for 75% of visits.

Across all visits, only 32.5% were guideline adherent for the first opioid dose (95% CI, 32.4-32.6%). For the 76.6% (n = 302,738) of visits with multiple doses, guideline adherence for the second dose was 9% (95% CI, 8.9-9.1%). Stratification by route of administration did not change adherence for the first dose, but investigators saw that orally administered opioids had higher guideline adherence at the second dose – 24.3% (95% CI, 23.7-24.8%) 0 compared to parental doses of 7.7% (95% CI, 7.6-7.8%) (

After univariate analysis, investigators saw that guideline adherence for the first dose was higher among patients aged ≤19 years (52%; 95% CI, 51.6-52.5%) compared to patients aged >19 years (29.6%; 95% CI, 29.5-29.8%) (

 <.001). This relationship held for the second dose. Additionally, male patients were more likely to receive guideline-adherent therapy compared to females for the first dose (36.9%; 95% CI, 36.7-37.1% vs 28.9%; 95% CI, 28.7-29.1%; 

 <.001) and the second dose (10.6%; 95% CI, 10.4-10.8% vs 7.7%; 95% CI, 7.6-7.9%; 

“There is a substantial gap we need to cover in terms of providing pain relief to patients in pain crises,” Gwarzo said. “Despite guidelines that have been around for nearly a decade, we are still falling behind for these patients, not providing enough pain relief for them in the emergency department.”

Editor's Note: Gwarzo reports a disclosure with the National Heart, Lung, and Blood Institute (NHLBI).

Gwarzo I, Dega HC, Brousseau D. Multicenter Evaluation of Guideline Adherence for the Timeliness of Pain Medication for Acute Sickle Cell Disease Pain. Abstract presented at the 67th American Society of Hematology Annual Meeting and Exposition. Orlando, FL. December 6-9, 2025.

Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 Guidelines for Sickle Cell Disease: Management of acute and chronic pain. Blood Advances. 2020;4(12):2656-2701. 

Videos

Gwarzo discussed the shortcomings faced by many patients with SCD during pain crises, due to less frequent opioid prescription than guidelines recommend.

New research on the sex differences in adults with stage 5 

 suggests the female survival advantage observed in the general population may not apply to women with kidney disease, with females >55 years of age less likely to survive or receive a kidney transplant than their male counterparts.

In the general population, women are more likely to outlive men by a 5.8-year gap, according to a previous study. In about 72% of 528 species of mammals, females live about 13% longer. Whether this mortality advantage persists in patients with chronic kidney disease has been previously unexamined.

“To our knowledge, no population-based study has examined sex differences in mortality and treatment among individuals with incident stage 5 CKD. Prior studies have reported lower hazards of all-cause mortality and death without receiving KRT in female individuals with CKD compared with male individuals,” wrote study investigator, Christian Chan, PhD, postdoctoral associate at Cumming School of Medicine. “However, these studies were based on nephrology-referred cohorts with less advanced disease, limiting generalizability to individuals with stage 5 CKD and potentially introducing bias if referral patterns differ by sex.”

To address this gap in research, investigators conducted a retrospective population-based cohort study leveraging data from administrative, laboratory, and provincial kidney programs in Alberta, Canada. The primary outcome assessed was all-cause death, found from Alberta Vital Statistics. Investigators established the study exposure as sex at cohort entry.

To compare mortality rates, investigators stratified patients by 5-year age groups and calculated female-to-male mortality rate ratios for the patient cohort and the general population. Stage 5 CKD was defined as sustained eGFR <15 mL/min/1.73 m2 for > 3 months.

The study included 7506 adults ≥ 18 years of age with incident stage 5 CKD. In the cohort, patients were categorized into groups of 18 to 44, 44 to 54, 55 to 64, 65 to 74, 75 to 84, and ≥ 84 years of age.

In the cohort, 54.9% of participants were male (n = 4121), and 45.1% were female (n = 3385). Investigators included individuals whose legal sex might not reflect that assigned at birth (<0.1%). Female individuals met stage 5 CKD criteria at older ages than male individuals (median [IQR] age at first documentation of stage 5 CKD, 74 [61-83] years vs 70 [58-80] years), with similar baseline eGFR and qualifying period by sex.

In a median 7.9-year follow-up, female individuals with stage 5 CKD experienced increased excess mortality than male patients, particularly at younger ages. Compared with the general population, standardized mortality ratios (SMRs) among those 20 to 44 years were 47.5 (95% Confidence Interval [CI], 34.7-60.3) for females and 12.0 (95% CI, 8.3-15.6) for males. At 65 to 74 years, SMRs were 14.1 (95% CI, 12.8-15.4) for females and 8.5 (95% CI, 7.9-9.2) for males, and by ≥85 years, SMRs were similar: 4.2 (95% CI, 3.9-4.5) for females and 4.1 (95% CI, 3.7-4.4) for males. Female-to-male mortality rate ratios showed a reversal of the usual female survival advantage in younger patients and a reduction in those with stage 5 CKD.

At 5 years after a stage 5 CKD diagnosis, female patients had 58.9% (95% CI, 57.2-60.7) crude risks of all-cause mortality compared with 51.9% of males (95% CI, 50.3-53.5). Death without receiving KRT occurred in 39.9% of females (95% CI, 38.3-41.6) versus 28.3% of males (95% CI, 26.9-29.7). In female patients, 8.5% (95% CI, 7.5-9.5) received a transplant compared to 14.5% of males (95% CI, 13.4-15.7).

Upon age-stratified analyses, investigators observed increased mortality in females <55 years, with similar risks between sexes in older age groups. In adjusted analyses, investigators increased all-cause mortality in females <45 years, increased death without kidney replacement therapy in those 65-74 years, and lower dialysis hazards in females ≥55 years.

“These findings highlight the need for further research into the biological, structural, and societal factors influencing sex differences in treatment decisions and survival,1” concluded investigators.

Chan C, Sawhney S, Ahmed SB, et al. Sex Differences in Mortality and Receipt of Kidney Replacement Therapy Among Adults With Stage 5 Chronic Kidney Disease. 

. Published online November 17, 2025. doi:

https://doi.org/10.1001/jamainternmed.2025.5979

Why do women live longer than men? A study offers clues to close the gap. NPR. Published October 6, 2025. 

https://www.npr.org/2025/10/06/nx-s1-5558184/women-men-longevity-health-life-span

Articles

Research indicates that the female survival advantage seen in the general population does not extend to women with stage 5 chronic kidney disease (CKD). Women over 55 with CKD are less likely to survive or receive a kidney transplant compared to men. A study in Alberta, Canada, found that females with stage 5 CKD have higher mortality rates, especially at younger ages, and lower rates of kidney replacement therapy. These findings suggest a need for further investigation into the factors affecting sex differences in CKD treatment and outcomes.

In women with CKD, there are no general survival advantages compared to the male patient population. 


Stage 5 CKD May Reverse Female Survival Advantage

A recent phase 3 study showed that lumateperone 42 mg as an adjunctive to antidepressant therapy provided statistically significant improvement in depression symptoms and disease severity by day 43 among individuals with 

This long-term pivotal data follows the US Food & Drug Administration (FDA) approval of lumateperone as an adjunctive therapy for MDD, announced by Johnson & Johnson on November 6, 2025. Lumateperone, an oral, once daily atypical antipsychotic, targets 3 neurotransmitters simultaneously: serotonin, dopamine, and glutamate. The drug acts as a 5-HT2A antagonist and modulates dopamine by partially agonizing presynaptic D2 receptors while blocking postsynaptic ones. It also influences D1 signaling, indirectly enhances AMPA and NMDA glutamatergic activity, and exhibits some CERT-inhibitory effects.”

“This complex mechanism, which includes all these 4 mechanisms, is the reason why we have seen a strong efficacy for this in this patient population,” said first author Suresh Durgam, MD, the chief medical officer and executive vice president at Intra-Cellular Therapies, in the

Podcast episode, December 2025: “December 2025: Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial.”

Durgam and colleagues conducted a phase 3, randomized, double-blind, placebo-controlled trial to assess lumateperone 42 mg as an adjunctive to antidepressant therapy in patients with MDD. Primary and secondary outcomes included change from baseline to day 43 in MADRS total score and Clinical Global Impressions Scale severity (CGI-S) score. Safety measures included adverse events, extrapyramidal symptoms, laboratory assessments, and suicidal ideation and behavior.

The sample included adults aged 18 – 65 years old who had DSM-5-defined MDD, an inadequate response to 1 or 2 antidepressant therapies in the current depressive episode, and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 24. Participants were randomized 1:1 to receive evening doses of lumateperone 42 mg plus their current antidepressant (n = 242) or placebo plus antidepressants (n = 238) for 6 weeks. The antidepressant used was the most recent medication to which the participant had shown an inadequate response (<50% improvement).

The trial met the primary and secondary endpoints, with lumateperone plus antidepressants significantly improving MADRS total score (least squares mean difference [LSMD] versus placebo, −4.5; effect size, −0.56) and CGI-S score (LSMD, −0.5; effect size, −0.51) versus placebo plus antidepressants at day 43. The lumateperone arm also had significantly improved patient-reported depression compared to the placebo arm at day 43 (16-item Quick Inventory of Depressive Symptomatology-Self-Report, total score, SMD, −2.2; effect size, −0.45)

The study also showed that lumateperone plus antidepressants was generally well tolerated, though more patients on lumateperone discontinued treatment due to treatment-emergent adverse events (12.4% vs 0.8%). Common adverse events included dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue. Lumateperone had a minimal risk of extrapyramidal symptoms and suicidal ideation; both arms had similar levels of cardiometabolic abnormalities and weight gain.

“This is not new from the standpoint of other atypical antipsychotics have been approved by the FDA for this purpose,” said Ned Kalin, editor-in-chief of the 

and psychiatry department chair at the University of Wisconsin, in the podcast. He listed currently approved antipsychotics: neuropeprazole, brexpiprazole, preprazole, cryptozone, and the combination medication olanzapine/fluoxetine.

“So, we do have other agents in this class of drugs that are already shown and are approved by [the] FDA to help people with depression,” Kalin continued. “But this is another medicine, and it's really helpful for us because it's not identical to the other medications.”

Durgam S, Earley WR, Kozauer SG, et al. Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial. 

. 2025;182(12):1072-1082. doi:10.1176/appi.ajp.20250292

FDA approval of CAPLYTA® (lumateperone) has the potential to reset treatment expectations, offering hope for remission in adults with major depressive disorder. JNJ.com. Published November 6, 2025. https://www.jnj.com/media-center/press-releases/fda-approval-of-caplyta-lumateperone-has-the-potential-to-reset-treatment-expectations-offering-hope-for-remission-in-adults-with-major-depressive-disorder

December 2025: Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial. Apple Podcasts. Published December 2025. Accessed December 8, 2025. https://podcasts.apple.com/us/podcast/december-2025-adjunctive-lumateperone-in-patients-with/id253702215?i=1000739105366

A phase 3 study demonstrated that lumateperone 42 mg, when used as an adjunctive therapy to antidepressants, significantly improved depression symptoms and disease severity in patients with major depressive disorder (MDD) by day 43. Following FDA approval, lumateperone targets serotonin, dopamine, and glutamate neurotransmitters. The trial met primary and secondary endpoints, showing significant improvements in MADRS and CGI-S scores. While generally well-tolerated, lumateperone had a higher discontinuation rate due to adverse events. This adds to the list of atypical antipsychotics approved for MDD treatment.

Following its 2025 FDA approval, lumateperone 42 mg demonstrated meaningful reductions in MADRS and CGI-S scores in adults with major depressive disorder.

Adjunctive Lumateperone Significantly Improves MDD Symptoms by Day 43 

Lindsay Rein, MD | Image Credit: Duke University School of Medicine

Bezuclastinib has displayed significant benefits on patient-reported symptoms and objective measures of mast cell (MC) burden, as well as demonstrated significant correlation between disease pathology and patient-reported symptom severity, in patients with 

nonadvanced systemic mastocytosis (NonAdvSM)

, according to results from the registration-directed part 2 of the phase 2 SUMMIT trial announced by parent company Cogent Biosciences, Inc.

 in Orlando, Florida, SUMMIT was a multicenter, randomized, double-blind, placebo-controlled phase 2 trial investigating bezuclastinib in patients with NonAdvSM who had inadequate symptom control despite best supportive care medications.

“Nonadvanced systemic mastocytosis patients currently have very limited treatment options, and the benefit of bezuclastinib demonstrated in the SUMMIT trial across measures of disease pathology and symptomatic improvement is very exciting for this patient population,” Lindsay Rein, MD, associate professor of medicine in the division of hematologic malignancies and cellular therapy at Duke University, said in a statement. “The SUMMIT trial results match my clinical experience using bezuclastinib with NonAdvSM patients, delivering rapid and deep improvement in symptom control and objective measures of disease without tolerability challenges.”

Part 2 of SUMMIT saw patients randomly assigned in a 2:1 ratio to either 100 mg bezuclastinib or placebo daily, in addition to best supportive care medication. The primary endpoint was 24-week mean change from baseline in Mastocytosis Symptom Severity Daily Diary (MS2D2) total symptom score. Secondary endpoints included the proportion of patients with ≥50% reduction in serum tryptase, 

 p.D816V variant allele frequency (VAF), bone marrow (BM), mast cell burden, and a ≥30% reduction in MS2D2 total symptom score.

Ultimately, investigators enrolled 179 patients; of these, 119 received bezuclastinib and 60 received placebo. The median age was 51 years (range, 23-78) and mean baseline MS2D2 total symptom score was 55.6 (standard deviation [SD], 19.8). Additionally, 82% of patients had indolent systemic mastocytosis (ISM), 11% had bone marrow mastocytosis (BMM), and 7% had smoldering systemic mastocytosis (SSM). At baseline, median 

 p.D816V VAF in whole blood, BM MC burden, and serum tryptase was 0.25% (range, 0-34%), 10% (1-75%), and 40 (6-692) ng/mL, respectively.

By week 24, patients receiving bezuclastinib exhibited substantially greater symptom improvement compared to placebo recipients (least-squares mean MS2D2 total symptom score change: -24.3; 95% CI, -27.6 to -21.1, vs -15.4; 95% CI, -19.6 to -11.2; 

 = .0002). A reduction of serum tryptase ≥50% was achieved by 87.4% of bezuclastinib recipients, versus 0% on placebo (

 <.0001). Additionally, significantly more patients receiving bezuclastinib saw ≥50% reductions in 

 = .01), and ≥30% reduction in MS2D2 total symptom score (

Consistent with data presented on July 7, 2025, most treatment emergent adverse events (TEAEs) were of low grade. The most frequent TEAEs reported on bezuclastinib treatment were hair color change (69.5% bezuclastinib vs 5% placebo), altered taste (23.7% bezuclastinib vs 0% placebo), and nausea (22% bezuclastinib vs 13.3% placebo). Serious adverse events occurred in 4.2% of patients receiving bezuclastinib, versus 5% of patients receiving placebo.

“We are excited to present additional data from the SUMMIT trial that support our conviction that bezuclastinib will be the best-in-class treatment option for patients with nonadvanced systemic mastocytosis,” Andrew Robbins, president and chief executive officer of Cogent Biosciences, said in a statement. “We remain on track to submit our first New Drug Application for bezuclastinib in NonAdvSM with the FDA this month.”

Cogent Biosciences has announced plans to present data from a 48-week follow-up period at an upcoming scientific meeting in Q1 2026.

Rein L, Boggs N, Bose P, et al. Efficacy and Safety Results from the Primary Analysis of the Pivotal SUMMIT Trial: Bezuclastinib in Adults With Non-Advanced Systemic Mastocytosis. Abstract presented at the 67

 American Society of Hematology Annual Meeting and Exposition. Orlando, FL. December 6-9, 2025.

Waarich C. Cogent Biosciences Presents Full SUMMIT Results of Bezuclastinib in Patients With Nonadvanced Systemic Mastocytosis (NonAdvSM) at the 67

 Annual Meeting of the American Society of Hematology (ASH). 

 December 6, 2025. Accessed December 8, 2025. 

https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-presents-full-summit-results-bezuclastinib

Bezuclastinib has shown significant efficacy in improving patient-reported symptoms and reducing mast cell burden in nonadvanced systemic mastocytosis (NonAdvSM) patients, as demonstrated in the phase 2 SUMMIT trial. The trial, presented at the ASH Annual Meeting, involved 179 patients and revealed substantial symptom improvement and reductions in serum tryptase and KIT p.D816V variant allele frequency. Bezuclastinib was well-tolerated, with most adverse events being low grade. Cogent Biosciences plans to submit a New Drug Application and present further data from a 48-week follow-up period in 2026.

Announced by Cogent Biosciences, these data indicate bezuclastinib’s capacity for improving patient-reported symptoms of mast cell burden.

SUMMIT: Bezuclastinib Outperforms Placebo in Nonadvanced Systemic Mastocytosis

The US Food and Drug Administration (FDA) has approved Ayrmid’s omidubicel-onlv (Omisirge) for the treatment of severe aplastic anemia (SAA), making it the first hematopoietic stem cell transplant therapy for this indication.

As described in a December 8, 2025, release from the FDA, with the approval, omidubicel-onlv is indicated for adults and pediatric patients ≥ 12 years of age with hematologic malignancies as well as adults and pediatric patients ≥ 6 years of age with SAA following reduced intensity conditioning and for whom a compatible donor is not available.

“The approval of [omidubicel-onlv] is a significant step forward in the treatment options available for patients with a high unmet medical need,” Richard Childs, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health, said in a statement.

“Patients in the study with aplastic anemia were high risk, but had significantly better than expected outcomes and demonstrated remarkably fast and high rates of neutrophil engraftment. This was achieved with low rates of mild acute GVHD and no chronic GVHD meaning the patients achieved a rapid return to a normal life.”

SAA is a rare, life-threatening blood disorder where the bone marrow fails to produce enough red blood cells, white blood cells and platelets. Treatment for SAA depends on age and consists of immunosuppressive therapy and/or hematopoietic stem cell transplant.

Omidubicel-onlv is a stem cell therapy where donated cord blood stem cells have been chemically enhanced with nicotinamide (a form of vitamin B3) and then given to a patient to help restore their blood and immune system. It addresses the limitations of umbilical cord blood as a source including delayed hematopoietic recovery and increased infections and provides additional graft options for patients with SAA who need hematopoietic stem cell transplant.

“This approval is revolutionary in the therapeutic landscape and fundamentally changes how we approach treatment for SAA, where earlier treatment has potential to alter one’s life course,” Vinay Prasad, MD, MPH, Chief Medical and Scientific Officer and Director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.

The approval is based on results from an ongoing open-label, single-center study in patients 6 years and older with SAA showing a median time to neutrophil recovery of 11 days, 86% of patients experiencing early and sustained neutrophil recovery at 100 days, rapid immune recovery post-transplant, and 86% of patients achieving red blood cell transfusion independence. Additionally, no cases of BMT-CTN severe acute graft-versus-host disease (GVHD), or chronic GVHD occurred, and a 92% disease-free and overall survival rate was observed.

The most common side effects associated with Omisirge include febrile neutropenia, viral and bacterial infections, hyperglycemia, immune thrombocytopenia and pneumonia. Autoimmune cytopenias have occurred in 25% of patients.

“[Omidubicel-onlv] is a novel stem cell product from umbilical cord blood that will be able to offer a therapeutic option for patients with severe aplastic anemia who have limited options for stem cell transplant,” said Megha Kaushal MD, MS, Acting Deputy Director of the CBER Office of Therapeutic Products and pediatric hematologist.

 “[Omidubicel-onlv] will shorten time to neutrophil recovery which leads to shorter recovery times after transplant and may improve infection rates in this patient population.”

Ayrmid. FDA approves Omisirge® as First Approved Cell Therapy to Treat Severe Aplastic Anemia. December 8, 2025. Accessed December 8, 2025. 

https://www.gamida-cell.com/press_release/fda-approves-omisirge-as-first-approved-cell-therapy-to-treat-severe-aplastic-anemia/

FDA. FDA Approves First Cellular Therapy to Treat Patients with Severe Aplastic Anemia. December 8, 2025. Accessed December 8, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-severe-aplastic-anemia

The FDA has approved omidubicel-onlv (Omisirge) for treating severe aplastic anemia (SAA), marking it as the first hematopoietic stem cell transplant therapy for this condition. This therapy is indicated for patients with hematologic malignancies and SAA who lack a compatible donor. Omidubicel-onlv, derived from chemically enhanced cord blood stem cells, addresses limitations of umbilical cord blood, offering rapid neutrophil recovery and high survival rates. The approval is based on promising study results, with minimal graft-versus-host disease and significant improvements in patient outcomes.

The approval of Ayrmid’s omidubicel-onlv makes it the first hematopoietic stem cell transplant therapy to treat patients with severe aplastic anemia.

FDA Approves Omidubicel-onlv (Omisirge) As First Cellular Severe Aplastic Anemia Therapy

Navigating Autoimmune Overlap in Celiac Disease, With Daniel Mallon, MD

The overlap between celiac disease and other autoimmune disorders, especially type 1 diabetes, is an increasingly important area of clinical focus. As research continues to illuminate shared genetic pathways and early-life influences, clinicians are working to refine screening strategies and improve care for patients who may develop multiple autoimmune conditions.

2025 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)

 Annual Meeting, Daniel Mallon, MD, a pediatric gastroenterologist at Cincinnati Children’s Hospital, explained that about 5-10% of patients with type 1 diabetes will also develop celiac disease, while a smaller proportion of patients with celiac disease later develop type 1 diabetes, a crossover he says is driven largely by shared HLA class genetics and additional single nucleotide polymorphisms. He notes that these common genetic features also link other autoimmune diseases like autoimmune thyroid disease to celiac disease and type 1 diabetes.

Mallon also highlights potential early-life environmental contributors, including viral infections, the timing of gluten introduction, and the amount of gluten consumed in toddler years. These factors, he says, may influence the development not only of celiac disease but also of other autoimmune conditions such as type 1 diabetes.

“When physicians, primary care doctors, endocrinologists are on the lookout for celiac disease, they obviously should be looking for the classic symptoms, malabsorption, diarrhea, weight loss, vomiting, GI symptoms, abdominal pain,” Mallon said. “But there are also other more subtle things, like slight delays in growth, or a great proportion of those patients have no symptoms at all, even when you ask a lot of questions.”

He goes on to note particular challenges in diagnosing celiac disease in patients with type 1 diabetes. He explains that false-positive serologies are common, making evaluation by a pediatric gastroenterologist essential. Such specialists can navigate the nuances of laboratory testing and help families manage the emotional burden of adding a second chronic condition.

Mallon further emphasizes why early identification matters, explaining how the combination of both conditions introduces unique risks that require tailored follow-up care. He also describes growing interest in screening patients with celiac disease for type 1 diabetes.

“If we can identify the patients before they get sick, then we can prevent DKA in 80 to 90% of those patients, which is an enormous help to their overall health,” he said.

Editors’ note: Mallon reports no relevant disclosures.

Mallon D. Crossroads Between Celiac Disease and Other Autoimmune Conditions. Session presented at 2025 NASPGHAN Annual Meeting. November 5-9, 2025. Chicago, Illinois.

UChicago Medicine. Are pediatric celiac disease and type 1 diabetes related? May 1, 2023. Accessed December 8, 2025. 

https://www.uchicagomedicine.org/forefront/pediatrics-articles/are-pediatric-celiac-disease-and-type-1-diabetes-related

Mallon explains the shared risks linking celiac disease and type 1 diabetes and why early screening improves outcomes.

Palliative Care Improves Outcomes in Patients with SCD, With Crawford Strunk, MD

Incorporating a palliative care team into a comprehensive 

 care center substantially reduced inpatient length of stay and improved outpatient pain management, according to a recent study.

 in Orlando, Florida, by Crawford Strunk, MD, associate staff member at the Cleveland Clinic, these data have emphasized the importance of further implementing interdisciplinary care in this largely underserved population.

SCD is an extremely morbid condition, with recurrent hospitalizations common for vaso-occlusive crises and complications of end-organ damage. Although prior research has indicated the effectiveness of palliative care in adult patients with SCD, a 2022 study examining data from 987,555 SCD-related hospitalizations showed that only 9.2% of cases received palliative care.

“The big picture for our results is that, if you have access to palliative care, our study demonstrates that integrating them into your sickle cell comprehensive care model is integral to helping reduce length of stay and improve outpatient and inpatient pain management,” Strunk told

 in an interview. “It also improves opioid stewardship and provides wraparound care for patients who suffer from chronic pain and acute-on-chronic pain.”

For this study, the Cleveland Clinic Department of Palliative and Supportive Care collaborated with the Cleveland Clinic Sickle Cell Medical Neighborhood (SCMN), which provides comprehensive lifespan care for patients with SCD. The SCMN includes medical and pediatric subspecialties, but did not initially include palliative care, individualized pain care plans, or guided inpatient pain management.

The SCMN and Department of Palliative and Supportive Care worked to formulate a structured program, with key interventions including the embedding of a palliative care consult and hematology consult trigger into the inpatient SCD hospital admission order set, the establishment of outpatient palliative care follow-up for outpatient pain management recommendations, and the development and implementation of Individualized Care Plans (ICPs) for high utilizing patients.

The inpatient palliative care and hematology consult trigger was activated in the inpatient SCD hospital admission order set in April 2024, and ICPs for high-utilizer patients were implemented in November 2024. From April 2024 to March 2025, enrollment in the SCMN grew from 190 patients to 231; during this time, the mean annualized hospitalization rate per patient decreased from 1.4 to 1.3 admissions per patient, and the mean inpatient length of stay for adults with SCD decreased from 9.1 to 3.2 days.

Additionally, during the study period, patients received care across multiple care settings, including quaternary care centers, community hospitals, and outpatient clinics. Regular interdisciplinary care meetings were shown to build confidence among palliative care and SCMN clinicians, which fostered improved opioid stewardship and the implementation of shared decision-making protocols.

Strunk highlighted reductions in inpatient length of stay and improvements in outpatient pain management resulting from the implementation of a palliative care team. Additionally, the study authors noted plans to continue examining the efficacy of palliative care regarding cost savings and broader applicability outside of SCD patients.

“What I also recommend is that if you have palliative care available through your cancer center or through an independent group, integrating them can be significantly helpful for pain management strategies and cost reduction for the hospitals in terms of services provided,” Strunk said.

Editor's Note: Strunk reports disclosures with Pfizer and Spark Healthcare.

Strunk C, Neale K, Albright C, et al. Integrating palliative care improves pain management and reduces length of stay in a comprehensive Lifespan Sickle Cell Center. Blood. 2025;146(Supplement 1):123-123. 

Nwogu-Onyemkpa E, Dongarwar D, Salihu HM, et al. Inpatient palliative care use by patients with sickle cell disease: a retrospective cross-sectional study. BMJ Open. 2022;12(8):e057361. Published 2022 Aug 16. 

Integrating a palliative care team into a sickle cell disease (SCD) care center significantly reduced inpatient length of stay and enhanced outpatient pain management. This interdisciplinary approach, presented at the ASH Annual Meeting, underscores the importance of palliative care in managing SCD, a condition marked by frequent hospitalizations due to vaso-occlusive crises. The Cleveland Clinic's collaboration led to a structured program with key interventions, resulting in decreased hospitalization rates and improved opioid stewardship. Future research will explore the cost-effectiveness and broader applicability of palliative care beyond SCD patients.

Strunk highlights reduced length of stay and superior outpatient pain management due to palliative care in hospitalized patients.

New research on finerenone treatment in patients with 

 receiving full supportive care has highlighted a significant reduction in the protein-to-creatinine ratio and stable estimated glomerular filtration rate (eGFR) during follow-up.

“Our previous study established that high levels of urinary sodium excretion, a surrogate for dietary sodium intake, were associated with poor renal outcomes in patients with IgA nephropathy,” wrote study investigator Jianghua Chen, the director emeritus and professor in the Kidney Disease Center, the First Affiliated Hospital of Zhejiang University, School of Medicine, and colleagues. “Finerenone may protect renal tissue by inhibiting the reabsorption of sodium ions by renal tubules, which need further mechanistic studies, such as Finerenone with SGLT2 inhibitor or more detailed mechanistic studies to clarify the protective pathway in IgA nephropathy.

Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist. In July 2021, the 

 approved the therapy to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease associated with 

American Society of Nephrology (ASN) Kidney Week 2025

. Investigators' research suggested a protective effect of finerenone on renal function, reduced risk of cardiovascular events, and a statistically significant 25% relative reduction in the urine albumin-to-creatinine ratio compared with the placebo in 6 months.

To evaluate finerenone’s impact in IgAN, Chen and colleagues conducted a retrospective, single-center analysis with follow-up visits at 2, 4, 6, and 8 months at the First Affiliated Hospital of Zhejiang University School of Medicine.

All patients had received full-dose renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) for > 12 weeks. Each patient received finerenone 10 mg daily for ≥3 months and was monitored every 1–3 months.

The study included 18 patients with IgAN receiving comprehensive supportive therapy, including RAS blockade, blood pressure control, and steroids and/or other immunosuppressive agents. Baseline proteinuria was 0.38 (0.28–0.75) g/g, and the average eGFR was 63.18 ± 22.01 mL/min/1.73 m².

At 2 and 6 months, investigators observed 28.48% (

 = .003) reductions in proteinuria, respectively, compared with baseline. At 8 months, proteinuria decreased 39.69%, falling from 0.38 (0.28–0.75) g/g to 0.24 (0.16–0.47) g/g (

Investigators further noted eGFR fluctuations at 2 and 4 months, 54.99 ± 27.49 mL/min/1.73 m² (

= .42) and 58.77 ± 15.78 mL/min/1.73 m² (

= .34), which were not statistically significant. Values remained stable through 6 and 8 months of treatment.

“These results suggest that finerenone is a promising therapeutic approach for reducing proteinuria in patients with IgA nephropathy,” investigators concluded.

Yu G, Wang M, Zhang X, et al. Effect of finerenone on proteinuria reduction in IgA nephropathy. 

 2025;47(1):2588501. doi:10.1080/0886022X.2025.2588501

https://www.sciencedirect.com/topics/medicine-and-dentistry/finerenone

McGill J. Finerenone Marks a Breakthrough for Kidney Protection in Type 1 Diabetes, With Janet McGill, MD, MA. HCPLive. November 11, 2025. Accessed December 8, 2025. 

https://www.hcplive.com/view/finerenone-breakthrough-kidney-protection-type-1-diabetes-mcgill

Finerenone treatment in patients with IgA nephropathy (IgAN) receiving full supportive care has shown a significant reduction in proteinuria and stable estimated glomerular filtration rate (eGFR) over an 8-month follow-up. The study involved 18 patients who had been on renin-angiotensin system blockade and received finerenone 10 mg daily. Results indicated a 39.69% reduction in proteinuria at 8 months, with eGFR remaining stable. These findings suggest finerenone as a promising therapeutic approach for reducing proteinuria in IgAN patients, warranting further mechanistic studies to clarify its protective pathway.

A retrospective cohort in finerenone showed nearly 40% proteinuria reduction at 8 months and stable eGFR in patients with IgA nephropathy.


Finerenone Shows Promise in IgAN: Reduced Proteinuria, Stable Kidney Function 

 with topical roflumilast 0.3% is an effective and safe option for patients, with new data showing the drug outperforms vehicle across clinician- and patient-reported outcomes.

Bibek Shrestha, MBBS, from Tribhuvan University Institute of Medicine in Nepal, led a team of other investigators in authoring the systematic review and meta-analysis leading to these findings. The investigators highlighted the promise of roflumilast, a selective phosphodiesterase-4 (PDE-4) inhibitor, as a therapeutic agent addressing concerns over cutaneous inflammation.

“While individual randomized trials have demonstrated clinical improvement with topical roflumilast, there is no systematic review that summarizes evidence on efficacy and safety in patients…” Shrestha et al wrote.

 “Thus, we performed this systematic review and meta-analysis to evaluate the efficacy and safety of topical roflumilast 0.3% in patients with plaque psoriasis.”

Design and Findings on Topical Roflumilast

The investigative team systematically searched, from their inception through May 2025, the Embase, Cochrane CENTRAL, ClinicalTrials.gov, and PubMed databases. They had sought to identify eligible RCTs for their analysis. Two independent reviewers were asked to screen all RCT titles and abstracts. They would determine which research fulfilled predetermined criteria for full-text evaluation. Any notable disagreements were resolved by the team through consultation with a third reviewer.

In their analysis, Shrestha and coauthors focused on several clinical endpoints in these RCTs, including Investigator’s Global Assessment (IGA) or body-IGA success, which was defined as attainment of clear or almost clear skin with a minimum 2-grade improvement from baseline. They also looked at data related to Psoriasis Area and Severity Index thresholds (PASI-50, PASI-75, PASI-90), to scalp-IGA (S-IGA), to intertriginous-IGA (I-IGA), and to PSSI-75, a score suggesting a 75% Psoriasis Scalp Severity Index improvement.

Additional outcomes highlighted by the investigative team included Numeric Rating Scale (WI-NRS) success attainment, Worst Itch, 8-week Psoriasis Symptoms Diary (PSD) scores, and reported occurrences of adverse events (AEs). The team's statistical calculations were done via Review Manager. They measured heterogeneity across RCTs with the Higgins I² statistic.

Across a set of 5 RCTs, involving 1835 study participants, Shrestha et al pointed to results suggesting topical roflumilast 0.3% led to significant increases in the rates of IGA/body-IGA improvement at the 8-week mark (RR 4.19; 95% CI 2.49–7.04; 

 They also noted substantial increases in S-IGA success (RR 3.37; 95% CI 1.57–7.25; 

 = .002) as well as I-IGA success (RR 3.32; 95% CI 2.11–5.22; 

Superior outcomes resulting from treatment with roflumilast were observed in PASI-50, PASI-75, PASI-90, and PSSI-75 scores.

 Relative risks were shown by the investigators to range from 2.55 to 4.32 (all 

 < .00001). PSD score improvements (MD –25.34; 95% CI –31.77 to –18.92) and WI-NRS improvements (RR 2.12; 95% CI 1.74–2.60) were likewise found to be significant. AEs were identified more frequently among individuals being treated with topical roflumilast (RR 1.29; 95% CI 1.08–1.54; 

While Shrestha and colleagues' findings in this systematic review and meta-analysis provide strong evidence suggesting topical roflumilast 0.3% psoriatic signs and symptoms improvements compared with vehicle, additional research was described as necessary to fill remaining gaps in the data. Future assessments were highlighted as needed to prioritize direct comparisons between roflumilast and other established topical drugs, with the aim being more clearly defining any distinctions in efficacy and safety across various psoriasis therapies.

“Combined with the favorable tolerability profile of topical 0.3% roflumilast, these key findings highlight topical roflumilast's potential to effectively and safely address the therapeutic needs of psoriasis patients,” Shrestha and coauthors concluded.

AA Khattak, A Javed, UA Rahman, et al. Clinical Efficacy and Safety of Topical Roflumilast in Psoriasis: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. JEADV Clinical Practice 0 (2025): 1-13, 

Hatzelmann A, Morcillo EJ, Tenor H, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2010 Aug;23(4):235-56. 

Topical roflumilast 0.3% has been shown to be an effective and safe treatment for plaque psoriasis, outperforming placebo in both clinician- and patient-reported outcomes. A systematic review and meta-analysis of five randomized controlled trials involving 1835 participants demonstrated significant improvements in various clinical endpoints, including Investigator’s Global Assessment and Psoriasis Area and Severity Index scores. While adverse events were more frequent with roflumilast, its favorable tolerability profile suggests it could effectively address therapeutic needs. Further research is needed to compare its efficacy and safety with other topical treatments.

This systematic review and meta-analysis looked at research on the efficacy and safety of topical roflumilast 0.3% in patients with plaque psoriasis.

Topical Roflumilast 0.3% Effective, Safe in Systematic Review of Psoriasis Data

Credit: University of California, San Diego

Pharvaris announced that RAPIDe-3 met its primary endpoint, with deucrictibant relieving 

The phase 3, placebo-controlled RAPIDe-3 trial evaluated deucrictibant, an oral immediate-release capsule (20 mg), for the on-demand treatment of HAE. Investigators evaluated this novel bradykinin B2 receptor antagonist in 134 participants aged ≥ 12 years from 24 countries on 6 continents.

“Bradykinin B2 receptor antagonism is a proven and effective mechanism for treatment of bradykinin-mediated angioedema,” said lead investigator Marc A. Riedl, MD, professor of medicine and clinical director of the US Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California, San Diego (UCSC), in a statement.

 “Injectable and oral on-demand therapies for HAE are available; however, unmet medical needs remain. The comprehensive and compelling outcomes of RAPIDe-3, specifically the fast treatment response and early complete symptom resolution, demonstrate the potential benefits of deucrictibant as an important on-demand treatment for people living with HAE.”

Riedl and colleagues assessed median time to treatment onset using the Patient Global Impression of Change (PGI-C); median time to substantial symptom relief using the PGI-C and Patient Global Impression of Severity (PGI-S); median time to complete symptom resolution using the PGI-S; and the percentage of attacks treated with a single capsule of deucrictibant. The sample included participants both on and off long-term prophylaxis; attacks of varying severity and across all body locations; and HAE subtypes, including type 1, type 2, and HAE with normal C1 inhibitor. This diverse population makes RAPIDe-3 highly representative and the first on-demand HAE study fully aligned with the Core Outcome Set recommended by the AURORA consensus.

Compared to placebo, participants on deucrictibant responded to the treatment quicker— within 1.28 hours, on average, vs > 12 hours (

 <.0001). Even minimal improvement, described as feeling “a little better,” counted as an onset of treatment response. Time to End of Progression 17.47 minutes for participants on deucrictibant vs 228.67 minutes for participants on placebo (

Participants treated with deucrictibant also experienced a shorter median time to substantial symptom relief on the PGI-C—rated as “better”—compared with placebo (2.85 hours vs > 12 hours; 

 <.0001). Time to substantial symptom relief by PGI-S4 ≥ 1-level improvement was 2.41 hours vs > 12 hours, respectively.

The median time to complete symptom resolution by PGI-S was significantly earlier with deucrictibant than placebo (11.95 hours vs > 24 hours; 

<.0001). Additionally, deucrictibant reduced attack burden: within 12 hours, 83% of attacks resolved with a single deucrictibant immediate-release capsule, and 93.2% of attacks required no additional rescue medication.

The study also showed that deucrictibant was well-tolerated with no treatment-related serious adverse events. The safety was consistent with completed and ongoing trials. Currently, investigators are conducting the ongoing RAPIDe-2 Part B, an open-label extension of deucrictibant for the on-demand treatment of HAE attacks.

“These clinically meaningful and statistically significant results demonstrate deucrictibant’s early-onset treatment response, fast symptom relief and resolution, and well-tolerated safety profile,” said Peng Lu, MD, PhD, chief medical officer of Pharvaris, in a statement.

 “This is an important step toward realizing deucrictibant’s potential to offer control of bradykinin-mediated angioedema attacks. With these data in hand, our team is working diligently to prepare for regulatory filings to enable access to this promising therapy.”

Pharvaris plans to submit a New Drug Application (NDA) for deucrictibant to the US Food & Drug Administration (FDA) in the first half of 2026. If approved, this would add yet another HAE treatment option for patients, building on the 

wave of HAE approvals seen in 2025, including garadacimab-gxii (Andembry), sebetralstat (Ekterly), and donidalorsen (Dawnzera)

, and setting the stage for the year ahead.

Pharvaris Announces Positive Topline Data from RAPIDe-3 Pivotal Study Confirming Potential of Deucrictibant for On-Demand Treatment of HAE Attacks - Pharvaris N.V. Pharvaris N.V. Published 2025. Accessed December 5, 2025. 

https://ir.pharvaris.com/news-releases/news-release-details/pharvaris-announces-positive-topline-data-rapide-3-pivotal-study

Soteres D, Tachdjian R, Manning M, et al. Rare Disease, Rapid Progress: FDA's HAE Approvals in 2025 Signal Changing Course. HCPLive. December 3, 2025. 

Pharvaris' RAPIDe-3 trial demonstrated that deucrictibant effectively alleviates hereditary angioedema (HAE) symptoms within 90 minutes. This phase 3 study, involving 134 participants, highlighted the drug's rapid onset and symptom resolution compared to placebo. Deucrictibant, a bradykinin B2 receptor antagonist, showed significant efficacy in reducing attack duration and was well-tolerated with no serious adverse events. The promising results pave the way for a New Drug Application submission to the FDA in 2026, potentially expanding HAE treatment options alongside recent approvals.

Oral bradykinin B2 receptor antagonist resolved HAE attacks in under 90 minutes, with most patients needing only a single dose and no rescue medication.


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