Pranav Garimella, MBBS, MPH, is chief medical officer of the American Kidney Fund.

For decades, a significant proportion of 

 in Black patients has been attributed to hypertension. This mislabeling may have obscured a distinct and underrecognized genetic driver, variants in the 

APOL1-mediated kidney disease (AMKD) affects an estimated 6 million African Americans who carry a high-risk genotype,¹ with approximately 13% of the self-identified African American population carrying two risk alleles that confer substantially elevated kidney disease risk.² Yet AMKD remains largely absent from routine clinical practice.

In recognition of the third annual AMKD Awareness Day, HCPLive spoke with Pranav Garimella, MD, Chief Medical Officer of the American Kidney Fund, about the scope of the misclassification problem embedded in the "hypertensive nephrosclerosis" diagnosis, the systemic and patient-level barriers slowing genetic testing uptake, and what nephrologists outside major academic centers should be doing differently — right now — for patients who carry two high-risk APOL1 variants.

The American Kidney Fund has described APOL1-mediated kidney disease as historically underdiagnosed, with many cases likely labeled as hypertension-associated kidney disease. How significant is that misclassification problem in practice, and how should nephrologists be rethinking patients currently labeled with 'hypertensive nephrosclerosis'?

The misclassification problem is real and clinically important. Hypertensive nephrosclerosis is often a diagnosis of exclusion, so some patients labeled that way actually have APOL1-associated kidney disease, FSGS, glomerulonephritis, or another primary kidney disorder. One biopsy-based study found that current clinical criteria for nephrosclerosis had very low sensitivity, 0.13, and even an optimized algorithm only rose to 0.19, while 40% of test-positive cases had other treatable diagnoses such as glomerulonephritis or interstitial nephritis.

In practice, that means nephrologists should be more skeptical of the label, especially in younger patients, those with proteinuria, hematuria, rapid eGFR decline, or an atypical course. Rather than accepting hypertension as the full explanation, we should rethink those cases as 'kidney disease with hypertension' and consider whether biopsy, genetic testing, or a broader workup is warranted.

Genetic testing for APOL1 is becoming more available, but uptake in clinical practice remains limited. What are the biggest barriers—clinical, systemic, or patient-level—to broader testing in high-risk populations, and where does responsibility for closing that gap ultimately fall?

Despite increasing availability of genetic testing, several barriers continue to limit its broader uptake in clinical practice. At the clinical level, many health care professionals remain uncertain about how to act on results, particularly if the downstream implications for treatment and monitoring are not clearly defined in guidelines. In addition, genetic testing is still not well integrated into routine clinical workflows.

At the patient level, awareness of APOL1 variants remains relatively low, even among high-risk populations. Concerns about genetic privacy, potential discrimination and mistrust of the healthcare system can further reduce uptake, particularly in communities that have historically been underserved or marginalized.

Addressing these gaps will require shared responsibility across stakeholders. Professional societies and researchers must develop consensus guidelines on monitoring, including incorporating genetic counseling services. To make meaningful progress, there needs to be equitable access, coverage for genetic counseling services, and an infrastructure. At the same time, community engagement and patient education are essential to building trust and awareness, requiring coordinated efforts across the care continuum.

The third annual APOL1-mediated kidney disease Awareness Day just passed. When you talk about 'awareness,' who is the primary target—patients, clinicians, or both? And what does meaningful awareness look like in practice versus awareness that doesn't change clinical care?

Both patients and clinicians. The American Kidney Fund is working to reach all of these audiences. Given how relatively recent the link between APOL1 and kidney disease was identified, we know that awareness among patients is low, and it's fair to say that health care professionals outside of nephrology likely have not received specialized education about AMKD.

For patients, awareness means understanding that APOL1 can be relevant to kidney disease risk and knowing when to ask questions or seek testing. For clinicians, especially outside nephrology, it means recognizing when APOL1 or AMKD should be part of the differential and when a "hypertensive nephrosclerosis" label deserves a second look. The new ICD code for AMKD is a big step forward as it gives clinicians a formal way to name APOL1-mediated kidney disease instead of forcing patients into nonspecific labels like hypertensive nephrosclerosis. In practice, that should improve recognition, data capture, family counseling, and trial referral.

Awareness only matters if it changes decisions such as diagnosis, counseling, testing, referral, or follow-up — not if it just increases familiarity with the term. Actionable awareness is the goal with the American Kidney Fund's efforts surrounding AMKD awareness.

With APOL1-targeted therapies in clinical trials, what should nephrologists outside of major academic centers be doing right now for a patient with two high-risk APOL1 variants—if anything differently today compared to standard chronic kidney disease management?

Nephrologists should treat the CKD phenotype, not just the genotype, using standard measures that slow progression: RAAS blockade when indicated, SGLT2 inhibitors when appropriate, BP control, statins when indicated, nephrotoxin avoidance, and sick-day counseling.

They should monitor closely if the patient is high risk. A two-risk-variant APOL1 genotype raises concern for progressive disease, so you should be more alert to rising albuminuria, falling eGFR, and faster-than-expected progression, but the treatment backbone remains standard CKD care.

Nephrologists should also discuss family member testing to identify other high-risk carriers who may need close monitoring as well, and refer to a clinical trial if eligible and if access exists.

Lastly, use shared decision-making. If discussing APOL1 results, explain that many people with two risk variants never develop kidney disease, so genotype is risk information, not an outcome. Partner with a clinical genetic counselor for better patient understanding.

Editor’s Note; Garimella reported no relevant financial disclosures.

Srinivasan V, So PN, Kwakyi EPK, Lerma EV, Wiegley N. APOL1 mediated kidney disease: a review and look toward the future. 

Pollak MR, Friedman DJ. APOL1 and APOL1-associated kidney disease: a common disease, an unusual disease gene — proceedings of the Henry Shavelle Professorship. 

Articles

APOL1 high-risk genotypes—present in ~13% of self-identified African Americans—may underlie kidney disease long attributed to hypertension, leaving millions with unrecognized AMKD. “Hypertensive nephrosclerosis” often functions as a low-specificity diagnosis of exclusion; biopsy data show poor clinical sensitivity and frequent alternative, treatable pathology. Broader APOL1 testing is slowed by unclear actionability, workflow gaps, limited counseling access, and privacy/mistrust concerns. A dedicated ICD code can improve recognition, data capture, counseling, and trial referral. Management remains phenotype-driven CKD care with intensified monitoring and shared decision-making.

Garimella, MBBS, unpacks what clinicians need to know about APOL1-mediated kidney disease, including misclassification, testing barriers, and management gaps. 

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Beyond Hypertensive Nephrosclerosis: A Closer Look at APOL1-Mediated Kidney Disease

Abigail Brooks is an assistant managing editor for 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

 remains one of the most common, but complex, gastrointestinal disorders in clinical practice. Defined by abdominal pain and altered bowel habits, IBS has historically been difficult to characterize, treat, and even explain to patients.

In recent years, the field has undergone a meaningful shift, with advances in understanding the gut-brain axis, microbiome, and underlying pathophysiology reshaping how clinicians approach diagnosis and management. At the same time, new therapies and evolving treatment strategies are expanding options for patients.

: clinical assistant professor at Rosalind Franklin University Chicago Medical School and director of the IBD program at Sinai Health System Chicago

: medical director of the GI Motility Program at Cedars-Sinai

: gastroenterologist with Baptist Health South Florida

As IBS Awareness Month highlights both progress and ongoing needs, experts emphasize a dual reality: care is improving, but major gaps remain.

For decades, IBS was categorized as a “functional” disorder, a label that often reflected uncertainty around its biological basis. Today, that framework is rapidly evolving.

“Our understanding of IBS has expanded significantly, leading to meaningful changes in how we approach disease management,” said 

 advisory board member Adelina Hung, MD. “It is increasingly recognized as a complex disorder of the gut-brain-microbiome rather than the traditional ‘functional’ condition.”

This shift reflects growing recognition that IBS arises from multiple interacting mechanisms, including dysregulation of the gut-brain axis, microbial imbalance, altered motility, immune activation, and visceral hypersensitivity. Rather than a single disease entity, IBS is now widely viewed as a spectrum of related conditions with overlapping features.

That complexity has important implications for care. Because the condition is highly heterogeneous with symptoms that vary widely between patients, standardized treatment approaches are inherently limited.

From Symptom Control to Targeted Management

Historically, IBS management focused on symptom relief, including antidiarrheals for IBS-D, laxatives for IBS-C, and general dietary advice. While these strategies remain important and still play an important role in care, they are no longer seen as sufficient as standalone approaches.

, Ali Rezaie, MD, noted that the field has moved away from purely empirical treatment toward more tailored strategies informed by underlying mechanisms.

“20 or 30 years ago, we would empirically treat patients, mostly just targeting symptoms,” he explained. “Now, we recognize that IBS has multiple underlying pathophysiologies, and depending on the patient, we can tailor therapy more precisely.”

For more from Rezaie on our evolving understanding of IBS treatment, check out 

Modern care begins with a thorough evaluation to exclude alarm features and conditions that may mimic IBS, such as 

 or malignancy. From there, clinicians can build a layered treatment approach that integrates lifestyle changes, pharmacotherapy, and targeted interventions based on symptom patterns and suspected drivers.

Dietary modification remains a cornerstone, but its effectiveness is often limited, with many patients ultimately requiring pharmacologic therapy and treatment selection guided by predominant symptoms such as constipation, diarrhea, or bloating.

Although several US Food and Drug Administration (FDA)-approved medications are now available, most continue to focus on symptom control rather than addressing root causes, a limitation that underscores the need for continued therapeutic innovation.

Recent years have brought important developments in IBS therapeutics, reflecting both incremental progress and broader shifts in treatment philosophy.

New investigational agents are exploring novel mechanisms across IBS subtypes, one of the most recent being EnteroBiotix Limited’s EBX-102-02, a next-generation oral full-spectrum microbiome therapeutic for IBS-C and IBS-D. In the phase 2a TrIuMPH trial, EBX-102-02 demonstrated clinically meaningful improvements in the IBS symptom severity score versus placebo, with clear separation from placebo observed as early as week 1 and sustained throughout the 6-week follow up period in both the IBS-C and IBS-D cohorts.

At the same time, regulatory milestones like the FDA approval of linaclotide (Linzess) for pediatric IBS-C are expanding access to care for younger patients. In November 2025, the guanylate cyclase C agonist from Ironwood Pharmaceuticals was approved for pediatric patients ≥ 7 years of age with IBS-C, making it the first treatment approved for IBS-C in this patient population.

Growing attention is also being paid to microbiome-directed therapies. Research suggests that, for some patients, alterations in the gut microbiome may play a central role in symptom development.

“There is no doubt that a subgroup of IBS patients has disease driven by the gut microbiome,” Rezaie said.

This recognition has supported the use of targeted interventions such as antibiotics, dietary strategies, and other microbiome-modulating approaches in select patients. However, identifying which patients will benefit most remains an ongoing challenge.

The Rise of Multimodal, Patient-Centered Care

As understanding of IBS has evolved, so has the approach to treatment. Care is increasingly being defined not by a single intervention, but by a combination of strategies tailored to the individual.

“Treatment involves a combination of diet, medications, lifestyle changes, and adjunctive therapy like CBT, hypnosis, acupuncture, and yoga,” Caroline Soyka, DO, told 

This multimodal framework reflects the interconnected nature of IBS pathophysiology, particularly the role of the gut-brain axis. Behavioral therapies, in particular, are gaining recognition for their ability to address symptom perception, stress response, and central processing of pain.

Rather than prioritizing one modality over another, Soyka said she approaches treatment as a collaborative process shaped by patient preferences, disease severity, and response to prior therapies. In a condition where no single treatment works universally, this flexibility is critical.

One of the defining features of IBS is its chronicity. Many patients are diagnosed in early adulthood and require long-term management, often with periods of symptom fluctuation.

“A lot of patients are diagnosed in their 20s, 30s, or 40s,” Rezaie said. “If you start them on a medication, this is not necessarily a curable disease, so they might be on that medication for years or decades.”

This reality makes expectation-setting a key component of care. Clinicians must balance the goal of symptom improvement with the understanding that complete resolution is often unrealistic.

Soyka emphasized the importance of reframing success for patients, particularly those with persistent or refractory symptoms.

“I remind [my patients] that we are not always aiming for perfection, but rather improvement each time,” she said.

This approach can help patients remain engaged in care while navigating the trial-and-error process that often accompanies IBS management.

Despite advances in understanding and treatment, IBS care often remains inconsistent in practice. One major challenge is the condition’s lack of a clear, algorithmic treatment pathway.

IBS requires individualized care, extensive patient education, and often ongoing adjustments to therapy, all of which are factors that can be difficult to accommodate in routine clinical settings. As a result, care may vary significantly depending on provider experience and available resources.

Soyka noted that many clinicians receive limited formal training in IBS, particularly in areas such as the gut-brain axis and microbiome-targeted therapies. This gap can contribute to variability in care and underutilization of certain treatment modalities. Access also remains a barrier, especially for non-pharmacologic interventions like cognitive behavioral therapy and complementary therapies, which are not always covered by insurance.

At the same time, real-world data suggest that these gaps continue to have a measurable impact on patients’ daily lives. Findings from the 2024 IBS in America survey indicate that IBS symptoms interfere with work productivity for nearly 11 days each month, while also disrupting personal and social activities for approximately 8 days monthly. Absenteeism has increased compared with prior years, and fewer than one-third of patients report being able to reliably predict when symptoms will occur, underscoring the persistent unpredictability of the condition.

Taken together, these data highlight a disconnect between advances in clinical knowledge and the lived experience of patients. While therapeutic options have expanded and understanding of IBS pathophysiology has deepened, many patients continue to face significant functional impairment and reduced quality of life.

Meanwhile, the underlying heterogeneity of IBS continues to complicate both diagnosis and treatment selection, reinforcing the need for more precise tools and biomarkers to guide care.

Looking Ahead: Precision Medicine and the Microbiome

The future of IBS care will likely be shaped by continued advances in microbiome science and precision medicine. Researchers are working to better characterize the diverse biological pathways involved in IBS and to identify targeted interventions for specific patient subgroups.

“The fecal microbiome holds so much of the key,” Soyka said.

However, translating this promise into clinical practice will require overcoming significant challenges. The microbiome is highly individualized and dynamic, making it difficult to define universal targets or standardized interventions.

Still, the broader trajectory of IBS research is clear: toward more personalized, mechanism-based care that moves beyond symptom management alone. As IBS Awareness Month underscores, the progress is real, but so is the work that remains.

NIDDK. Irritable Bowel Syndrome (IBS). November 2017. Accessed April 30, 2026. 

https://www.niddk.nih.gov/health-information/digestive-diseases/irritable-bowel-syndrome/definition-facts

Brooks A. EBX-102-02 Shows Benefit for IBS-C and IBS-D in Phase 2a TrIuMPH Trial. HCPLive. January 28, 2026. Accessed April 30, 2026. 

https://www.hcplive.com/view/ebx-102-02-shows-benefit-for-ibs-c-and-ibs-d-in-phase-2a-triumph-trial

Brooks A. FDA Approves Linaclotide (Linzess) Capsules for Pediatric IBS-C. HCPLive. November 5, 2025. Accessed April 30, 2026. 

https://www.hcplive.com/view/fda-approves-linaclotide-linzess-capsules-for-pediatric-ibs-c

Rezaie A. Rethinking IBS Management: The Shift Toward Precision Care, With Ali Rezaie, MD. HCPLive. April 13, 2026. Accessed April 30, 2026. 

https://www.hcplive.com/view/rethinking-ibs-management-the-shift-toward-precision-care-with-ali-rezaie-md

Brooks A. Positive Psychological Gut-Brain Behavior Therapy Shows Early Benefit for IBS. HCPLive. August 29, 2025. Accessed April 30, 2026. 

https://www.hcplive.com/view/positive-psychological-gut-brain-behavior-therapy-shows-early-benefit-for-ibs

AGA. IBS in America: Despite advances, IBS remains a burden for many millions. August 7, 2025. Accessed April 30, 2026. 

https://gastro.org/press-releases/ibs-in-america-despite-advances-ibs-remains-a-burden-for-many-millions/

AGA. Landmark Survey Reveals Physical and Emotional Challenges Faced by Patients Living with IBS. April 12, 2016. Accessed April 30, 2026. 

https://gastro.org/press-releases/landmark-survey-reveals-physical-and-emotional-challenges-faced-by-patients-living-with-ibs/

Irritable bowel syndrome is increasingly viewed as a heterogeneous gut–brain–microbiome disorder driven by interacting mechanisms including dysbiosis, motility disturbances, immune activation, and visceral hypersensitivity. Management is shifting from empiric symptom suppression to mechanism-informed, layered care after exclusion of alarm features and mimicking disease. Therapeutic options are expanding, spanning FDA-approved agents (including pediatric linaclotide) and investigational microbiome therapeutics such as EBX-102-02. Multimodal strategies incorporating dietary, pharmacologic, and behavioral interventions are emphasized, yet real-world care remains variable, burdensome, and in need of biomarkers to enable precision treatment.

IBS care is evolving with personalized, multimodal strategies, but gaps in access, education, and real-world outcomes continue to impact patients’ lives

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Navigating Progress, Personalization, and Persistent Gaps in IBS Care

IL-23 or IL-17 for Preventing Psoriasis Progression into PsA, With Andrew Blauvelt, MD, MBA

The longstanding debate over IL-23 versus IL-17 inhibitors in moderate to severe plaque psoriasis has largely been framed around skin clearance — a competition that most experts characterize as effectively too close to call. At the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, Colorado, that debate extended to a more clinically consequential and mechanistically charged question: whether biologic class selection in psoriasis patients without current joint involvement might determine who goes on to develop psoriatic arthritis.

Andrew Blauvelt, MD, MBA, owner of Blauvelt Consulting, in Annapolis, Maryland, and a principal investigator on the ONWARD program, argued the affirmative in a formal debate at the meeting, with Richard Langley, MD, professor of dermatology at Dalhousie University in Halifax, Nova Scotia, taking the opposing view. The debate drew on an emerging body of observational evidence suggesting that treatment with IL-23 pathway inhibitors — agents targeting the IL-23p19 subunit such as guselkumab, risankizumab, and iltaekizumab — may reduce the rate of PsA development in patients with psoriasis who do not yet have joint disease.

The clinical context for the debate is well established. Up to 30% of patients with psoriasis develop PsA over their disease course, with a lag of 5 to 7 years on average between skin and joint onset — a window that, in principle, creates an opportunity for preventive intervention. IL-17 inhibitors are currently regarded by most experts as the preferred biologic for patients who already have established PsA, given their more robust joint outcome data from controlled trials. The more provocative and contested question is whether IL-23 inhibitors might have a distinct preventive role upstream of PsA onset — a hypothesis Blauvelt characterized as biologically coherent in a conversation with 

IL-23 is an orchestrator cytokine sitting proximal to multiple downstream inflammatory cascades, including the IL-17 axis; inhibiting it theoretically disrupts the upstream regulatory signal before it can drive synovio-entheseal inflammation, rather than blocking the downstream effector cytokine once the inflammatory cascade is already established.

Several observational analyses have provided preliminary support for this hypothesis. Real-world studies of patients with psoriasis and early musculoskeletal symptoms treated with IL-23 inhibitors have reported lower rates of PsA progression compared with historical rates and with patients on other biologic classes. The ongoing PAMPA (Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort) trial, a randomized, double-blind, placebo-controlled phase 4 study, is directly testing this hypothesis prospectively, with guselkumab versus placebo in psoriasis patients at elevated PsA risk; co-primary endpoints include a power Doppler ultrasound musculoskeletal score at week 24 and the proportion of patients with new PsA at week 96. PAMPA data are not yet mature.

The central methodological objection to the existing observational evidence — and the core of Langley's opposing argument — is selection bias. In routine practice, patients with any musculoskeletal symptoms are more likely to be placed on IL-17 inhibitors, which have established joint efficacy, while patients without joint involvement are more likely to receive IL-23 inhibitors. If this prescribing pattern holds across the observational datasets, then the apparently lower PsA incidence in IL-23-treated cohorts may simply reflect the fact that those patients were less predisposed to joint disease at baseline — not that the drug prevented it. Conversely, IL-17-treated cohorts may appear to have higher PsA rates because they were enriched for patients already on a joint disease trajectory. Blauvelt acknowledged this confounding risk directly, framing it as the critical limitation of the current literature and the reason prospective randomized data from PAMPA and similar trials are needed to settle the question.

The debate did not yield a consensus — nor was it designed to — but it distilled the clinical decision point that will face dermatologists as the evidence base matures: whether, for a psoriasis patient without current joint symptoms but with risk factors for PsA progression such as nail disease, scalp involvement, high body mass index, or a family history of PsA, IL-23 inhibition should be considered not only for skin control but as a strategy to delay or prevent joint disease onset. Blauvelt's position is that the mechanistic rationale is compelling and the emerging observational data are hypothesis-generating enough to take seriously, even before prospective confirmation. Langley's counterpoint is that prescribing decisions of this magnitude require randomized evidence that does not yet exist, and that acting on biologically plausible but methodologically compromised data risks systematically misallocating treatment in a disease where IL-17 inhibitors offer established and proven joint protection.

“Anybody with any kind of musculoskeletal disease may have preferentially been put on 17 blocker, and then they may be more predisposed to develop PsA. So that's the controversy. I'm taking the stance that 23 blockers do indeed have the potential to block PsA,” Blauvelt said.

Langley RG, Blauvelt A. Debate: IL-23 versus IL-17 inhibitors — does biologic class prevent psoriatic arthritis development? Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

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Are IL-23 inhibitors, rather than IL-17 inhibitors, the preferred biologic for psoriasis patients at risk of developing psoriatic arthritis?

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Leena Shahla, MD, is the medical director at the Duke Pituitary Center and an associate professor of medicine and neurosurgery at Duke University.

Real-World Data Reinforces Paltusotine’s IGF-1 Reductions in Acromegaly, With Leena Shahla, MD

Paltusotine reduces insulin-like growth factor 1 (IGF-1) levels in adult patients with 

 while lessening treatment burden and without new safety signals, based on a recent study.

American Association of Clinical Endocrinology (AACE) Annual Meeting 2026

 in Las Vegas, Nevada, by Leena Shahla, MD, medical director at the Duke Pituitary Center and associate professor of medicine and neurosurgery at Duke University, these data highlight the safety and efficacy of paltusotine, as well as its capacity for reducing injection burden in adult patients.

“These injections are not easy – they’re painful, they may cause bruises, tenderness, patients worry about where and how to take them,” Shahla told 

 in an exclusive interview. “They may need an office visit every month to take the injection, or they may need home visits by a nurse to help with the injection, which will affect their schedule. Having another option like paltusotine, an oral medication, is excellent for patients.”

, under the name PALSONIFY. The decision was based on a pair of pivotal phase 3 trials, PATHFNDR-1 and PATHFNDR-2, which displayed paltusotine’s safety and efficacy in medically untreated adults with acromegaly. Paltusotine exhibited rapid onset, sustained efficacy, and reliable biochemical control throughout both trials.

The present study included adult patients with a confirmed diagnosis of acromegaly who had been prescribed paltusotine at 1 of 3 US-based pituitary centers and who had ≥1 IGF-1 level available after drug initiation. Medical records were scanned for demographic and clinical characteristics, treatment history, IGF-1 levels, acromegaly symptoms, and paltusotine dosing.

A total of 6 patients were enrolled in the study. Patient ages ranged from 25 to 58 years, and all patients had undergone a prior pituitary adenoma resection. 3 of these patients had no history of acromegaly medications, while the others had received and eventually discontinued lanreotide, ocreotide, carbergoline, or any combination of these drugs. Each patient received a dose of paltusotine between 20 and 40 mg per day.

At baseline, IGF-1 levels ranged from 304 to 674 ng/mL. After 3-4 weeks, IGF-1 levels dropped to around 164-281 ng/mL in all but 1 patient. The upper limit of normalized IGF-1 ranged from 328 to 347 ng/mL across all 3 study centers.

Additionally, Shahla and colleagues analyzed individual patient outcomes before and after treatment. After 3-4 weeks of treatment, patient 1 saw more regular menses, resolved joint pain, and increased energy, among other outcomes. Patient 2 saw improved sleep and sleep apnea, improved blood pressure, smoother facial features, and increased energy. Patient 3 saw a reduction in speech slurring and resolution of headaches, while patient 4 saw improved sleep and decreased joint pain and sweating. Patient 5 saw their hand joint pains resolved and their headaches improved, while Patient 6 saw improved blood glucose levels after treatment.

Shalha and colleagues determined that this study proved paltusotine’s efficacy and reinforced its safety profile. However, the team also encourages additional real-world studies, including larger sample sizes.

“Rather than worrying or going through the struggles with the injections and the pain and the hassle, taking oral medication is easier,” Shahla said. “It’s more convenient, and it will maintain their biochemical and symptom control. If a patient would rather avoid an injection, they now have the option to.”

Editors’ Note: Shahla reports disclosures with Camurus, Chiesi Farmaceutici, Crinetics Pharmaceuticals, and Recordati Rare Diseases.

Shahla L, Galbiati F, Blevins L, Yuen K. Once-Daily Oral Paltusotine in the Treatment of Adults With Acromegaly: Initial Real-World Experience. Presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.

Crinetics Pharmaceuticals. Crinetics Announces FDA Approval of PALSONIFY (paltusotine) for the Treatment of Acromegaly in Adults. September 25, 2025. Accessed April 30, 2026. 

https://crinetics.com/press-releases/crinetics-announces-fda-approval-of-palsonify-paltusotine-for-the-treatment-of-acromegaly-in-adults/

Shahla discusses a recent real-world study analyzing the clinical outcomes of patients prescribed paltusotine after its September 2025 approval.

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Adriana Le Thanh-Thao, MBBS, FRACP, from the Royal Hobart Hospital Jack Jumper Allergy Program.

demonstrated similar protection to standard 50 mcg dosing, with 85% of participants tolerating a sting challenge after 12 months.

These findings come from a phase 1/2 single-blind randomized controlled trial of 49 adults aged 18 – 65 years with prior systemic allergic reactions to JJA stings, with 44 initiating treatment (either 25 mcg venom + delta-inulin (n = 10), 25 mcg venom with no delta-inulin (n = 11), 50 mcg venom + delta-inulin (n = 12), or 50 mcg venom with no delta-inulin (n = 11)) and 40 undergoing a sting challenge. Investigators observed no difference between dosing groups (odds ratio [OR], 0.89; 95% CI, 0.38–2.09; 

 =.98) or with the addition of delta-inulin (Advax) (OR, 0.99; 95% CI, 0.42–2.33). Greater dosing reduced systemic reactions (OR, 0.53; 95% CI, 0.28–0.98).

 spoke with investigator Adriana Le Thanh-Thao, MBBS, FRACP, from the Royal Hobart Hospital Jack Jumper Allergy Program to contextualize these findings for clinical practice. In this Q&A, Le Thanh-Thao discussed dose selection, safety trade-offs, the role of delta-inulin, and how clinicians should interpret emerging biomarker data in venom immunotherapy.

 What do the findings suggest about the comparative efficacy of 25 mcg versus 50 mcg maintenance dosing for jack jumper ant venom immunotherapy?

 85% of participants who completed the trial protocol passed [the] deliberate sting challenge after 12 months of maintenance [with] JJA VIT. The sting challenge outcomes were similar between the 25mcg and 50mcg VIT groups, suggesting low-dose JJA VIT may be non-inferior to the current standard dose.

 Given similar efficacy, what are the potential advantages and trade-offs of using a lower 25 mcg maintenance dose in clinical practice?

 JJA venom for VIT is costly and resource-intensive to produce. A lower maintenance dose would be associated with significant healthcare savings for the institutions providing JJA VIT and potentially increase the capacity to treat more patients.

Shortages of JJA venom are a risk, as there is only one manufacturer of the product, and a lower maintenance dose would mitigate the impact of a shortage should it occur.

It is unknown if the 25 mcg dose is protective against multiple stings or will be less likely than higher VIT doses to induce mechanisms of long-term immune tolerance, which are desired to provide ongoing protection from stings after completing a 3–5-year course of VIT.

While we expected a lower VIT dose to be associated with [fewer] allergic side effects (as has previously been found when comparing 50 mcg vs. 100 mcg JJA VIT), in our current study, systemic allergic reactions were more common with the lower VIT dose. Further studies would be required to determine if this is a true effect, in which case it may reflect the observation that some patients require a higher VIT dose compared to others to induce tolerance.

 How did the addition of delta-inulin influence clinical outcomes, and should it be considered in routine venom immunotherapy protocols?

 Advax enhanced sIgG4 responses when combined with the standard JJA VIT dose, but this did not correlate with an improvement in clinical outcome in terms of either efficacy or treatment-related side effects. As a result, it should not yet be considered in routine VIT protocols. Advax may still have immunomodulatory benefits with longer-term VIT treatment, including after cessation of treatment, but this would require further studies.

 How should clinicians weigh the finding that greater maintenance dosing was associated with fewer treatment-related systemic reactions?

 The number of participants in this study was relatively small, so it is possible this is a chance result, and a larger study would be required to confirm this finding. However, it is well recognized that some bee and wasp venom-allergic patients do not have clinical protection with standard 100 mcg maintenance dosing, which is evidenced by systemic reactions to VIT or stings while in the maintenance phase of therapy. Increasing to a higher VIT maintenance dose (e.g., 200 mcg) in these patients has been shown to confer protection. It may be a similar scenario with the low-dose JJA VIT patients having systemic reactions to VIT, requiring a higher dose to induce tolerance.

 What do the safety data indicate about the risk of systemic reactions during the build-up versus maintenance phases of therapy?

 Systemic reactions are most common during the build-up phase and uncommon during the maintenance phase of therapy. While systemic reactions to JJA VIT are common, occurring in around one-third of patients when using a semi-rush build-up protocol, the majority of these reactions are mild and non-recurrent.

 How might basophil activation test trends inform clinical decision-making or risk stratification in venom immunotherapy?

 This study found a decrease in basophil activation from baseline was associated with having a negative sting challenge after 12 months of VIT. A decline in BAT sensitivity, therefore, has the potential [to be] a biomarker for predicting the development of clinical tolerance to stings. However, these findings would need to be replicated in larger studies to confirm BAT’s robustness as a biomarker of successful VIT.

 In the absence of clear biomarker predictors, how should clinicians currently assess treatment success and protection against future stings?

 At present, there is still no established biomarker for gauging VIT success, which is instead assessed clinically by reactivity to stings (either accidental field stings or with deliberate sting challenge) during and after a course of VIT. However, while stings are the ‘gold standard’ test, they have some limitations in regard to their negative predictive value. Tolerance to a single sting during or following a course of VIT is still not a guarantee of tolerance to subsequent stings, as the natural history of reactivity to stings is variable in allergic patients, who may tolerate their next sting [and] then react to a subsequent sting.

 Based on these findings, is there sufficient evidence to support adopting lower-dose venom immunotherapy?

 This was a pilot phase 1/2 study, and the number of participants was relatively small. Larger studies would be required to confirm the non-inferiority of lower VIT dosing.

Le TA, Wanandy T, Perkins GB, et al. A Pilot Randomised Controlled Dose-Ranging Trial of Ant Venom Immunotherapy With and Without Delta-Inulin Adjuvant. 

Q&A with Le Thanh-Thao on trial data showing 25 mcg of JJA VIT matched 50 mcg efficacy, with safety and biomarker insights.


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Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

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