Experts discuss which outcome instruments are most useful in routine clinical practice and address how patients' tendency to underreport disease burden before experiencing effective treatment affects baseline severity assessment and escalation decision-making.

Outcome Instruments in Practice and Baseline Underreporting in Untreated CSU

Chronic spontaneous urticaria is assessed through several validated instruments that measure distinct but related dimensions of disease: the daily UAS and UAS7 quantify objective disease activity through hive count and itch severity; the Urticaria Control Test (UCT) captures the patient's own perception of disease control; and the Dermatology Life Quality Index (DLQI) measures the broader impact of disease on daily functioning. The updated international guidelines recommend UAS7 and UCT as primary monitoring tools for CSU, with provocation thresholds added for inducible subtypes. In clinical practice, however, implementing a multi-instrument assessment consistently across a busy practice requires deliberate workflow integration, and not all instruments are equally accessible or practical in every clinical setting.

A recurring pattern across multiple CSU data sets — including the REMIX-1/-2 remibrutinib analyses — is that the correlation between UAS7 and UCT is moderate at baseline but strengthens substantially once effective treatment is underway. This dynamic reflects a clinically important phenomenon: patients who have lived with poorly controlled CSU for months or years may lack a meaningful reference point for what disease control actually feels like, and as a result may underreport the degree to which their disease is affecting them at the time of initial evaluation. The implication is that pre-treatment severity assessments, while necessary, may systematically underestimate true disease burden — and that the full impact of untreated CSU may only become legible to both patient and clinician retrospectively, once effective therapy has established a new baseline for comparison.

In this final segment of the video discussion on CSU management updates, Steve Dorman, MD, notes that this underreporting dynamic has direct implications for escalation decisions: a patient whose baseline UCT or UAS7 appears only moderately abnormal may in fact be carrying a heavier burden than the scores reflect, and clinicians should weigh that possibility when deciding whether to advance therapy. Eric Karlin, MD, adds that in his practice he captures both UAS7 and UCT routinely, finding that the 2 instruments together provide a more complete picture than either alone — and that watching the UCT rise in parallel with falling UAS7 scores as treatment takes effect is itself one of the more reliable signals that a step-up therapy is producing genuine disease control rather than partial or transient relief.

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Patrick Campbell is the editorial director of HCPLive. Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter and/or multimedia specialist with the Pocono Record, Star News Group, and NJ Advance Media. He is the executive producer for multiple HCPLive podcasts, including Diabetes Dialogue, Don't Miss a Beat, Kidney Compass, Medical Ethics Unpacked, The Medical Sisterhood, and Skin of Color Savvy. 


Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Ashley Shoemaker, MD, MSCI
Credit: Vanderbilt Health

 has approved an expanded indication for setmelanotide (Imcivreee) to treat acquired hypothalamic 

 (HO) in adults and pediatric patients aged 4 years and older, the company announced on March 19, 2026. 

According to Rhythm Pharmaceuticals, the approval makes setmelanotide the first and only FDA-approved therapy for this rare condition, which is characterized by accelerated and sustained weight gain following injury to or dysfunction of the hypothalamus.¹

“Setmelanotide has shown effectiveness in targeting the underlying biology of acquired HO,” said Ashley Shoemaker, MD, MSCI, associate professor of pediatrics and pediatric endocrinology at Vanderbilt Health. “Patients treated with setmelanotide experienced meaningful reductions in BMI and hunger, demonstrating the therapy’s ability to deliver clinically significant outcomes in both children and adult patients. Acquired HO is a severe disease that requires early and proactive management. With the availability of IMCIVREE, physicians can offer a targeted therapy.”¹

The approval was based on data from the global, randomized, double-blind, placebo-controlled phase 3 TRANSCEND trial enrolling 142 patients with acquired HO aged 4 years and older. According to the company, participants were randomized 2:1 to receive once-daily subcutaneous setmelanotide, titrated up to 1.5 to 3.0 mg depending on age, weight, and tolerability, or placebo for 52 weeks.¹

The trial met its primary endpoint. Patients on setmelanotide (n=94) achieved a mean BMI reduction of 15.8% from baseline at 52 weeks, compared with a 2.6% increase in the placebo arm (n=48), yielding a placebo-adjusted BMI reduction of 18.4% (

 <.0001).¹ The result built on earlier phase 2 findings published in 

, in which 89% of 18 patients with hypothalamic obesity met the primary endpoint of at least a 5% BMI reduction after 16 weeks of setmelanotide treatment, with a mean BMI reduction of 15% across the study population.²

Setmelanotide was generally well tolerated in TRANSCEND, the company noted. Adverse events occurring in more than 20% of participants included skin hyperpigmentation, nausea, vomiting, and headache. 

According to prescribing information, patients with acquired HO and secondary adrenal insufficiency experienced serious adverse reactions related to acute adrenal insufficiency in 5% of setmelanotide-treated patients, and sodium imbalances, including both hyponatremia and hypernatremia, were observed in patients with concomitant central diabetes insipidus. Depression and suicidal ideation have also been reported with setmelanotide across indications and warrant monitoring.¹

A Rare Disease With No Prior Approved Options

Acquired HO most frequently follows the growth or treatment of craniopharyngioma, astrocytoma, or other hypothalamic-pituitary tumors, though traumatic brain injury, stroke, and inflammatory causes are also recognized. Hypothalamic injury disrupts MC4R pathway signaling, resulting in impaired regulation of hunger and energy expenditure, driving rapid and often severe weight gain that proves resistant to conventional anti-obesity approaches. Rhythm estimates there are approximately 10,000 people in the US living with the condition, though the company acknowledged that figure is based on analysis of published literature, tumor registries, and claims data.¹

Setmelanotide is an MC4R agonist that Rhythm describes as designed to restore impaired MC4R pathway signaling. It was first approved by the FDA in 2020 for adults and pediatric patients aged 6 years and older with obesity due to POMC, PCSK1, or LEPR deficiency, and subsequently for Bardet-Biedl syndrome, establishing a prior regulatory track record in MC4R pathway-driven rare obesity.³ The acquired HO approval represents the first indication extending setmelanotide to an obesity phenotype driven by structural rather than genetic disruption of that pathway.

Rhythm Pharmaceuticals, Inc. Rhythm Pharmaceuticals announces FDA approval of IMCIVREE (setmelanotide) for patients with acquired hypothalamic obesity. Press release. Published March 19, 2026. Accessed March 19, 2026. 

https://ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-fda-approval-imcivreer-1

Roth CL, Schulten S, Meeker D, et al. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. 

 2024;12(6):385-393. doi:10.1016/S2213-8587(24)00085-8

Walter K. FDA approves setmelanotide for obesity caused by genetic deficiencies. 

 Published November 27, 2020. Accessed March 19, 2026. 

https://www.hcplive.com/view/fda-setmelanotide-obesity-genetic-deficiencies

Articles

FDA expanded setmelanotide (Imcivree) to treat acquired hypothalamic obesity in adults and children aged ≥4 years, establishing the first approved therapy for this rare, injury-related obesity phenotype. In the phase 3 TRANSCEND trial (n=142), once-daily SC setmelanotide produced a 15.8% mean BMI reduction at 52 weeks versus a 2.6% BMI increase with placebo (placebo-adjusted −18.4%; P<.0001), with parallel hunger improvements. Safety was consistent with prior use, with specific monitoring considerations in adrenal insufficiency, central diabetes insipidus, and mood symptoms.

FDA clears setmelanotide for acquired hypothalamic obesity for ages 4 years and older, delivering 15.8% BMI drop in TRANSCEND.

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FDA Approves Setmelanotide (Imcivree) for Acquired Hypothalmic Obesity

Experts review a phase 2 exploratory analysis of barzolvolimab in CSU, examining off-treatment efficacy at 28 weeks after the final dose, complete response rates, and quality-of-life outcomes among patients who achieved well-controlled disease after 52 weeks of treatment.

Barzolvolimab Post-Treatment Durability —Off-Treatment Data, Complete Response Rates, and Quality-of-Life Outcomes

Among the most clinically striking findings to emerge from recent urticaria research is evidence that therapeutic benefit in CSU may persist substantially beyond the cessation of active treatment — a pattern observed in a phase 2 exploratory analysis of barzolvolimab, an anti-KIT monoclonal antibody targeting the mast cell stem cell factor receptor, presented at the 2026 American Academy of Allergy, Asthma & Immunology meeting. The analysis examined patients who completed 52 weeks of barzolvolimab — at doses of either 150 mg every 4 weeks or 300 mg every 8 weeks — and achieved at least well-controlled disease, defined as a UAS7 of 6 or less, at week 52. Of 55 qualifying patients, 48 had data available at week 76. At study entry, 71% of this subgroup had severe disease and the mean UAS7 was 31.5 at baseline — a substantially burdened population. By week 52, 87% had achieved a complete response (UAS7 = 0) and 13% had well-controlled disease.

The off-treatment follow-up data are notable on multiple levels. At week 76 — 28 weeks after the final dose — 50% of patients maintained a complete response and 19% maintained well-controlled disease, with approximately 69% maintaining at least well-controlled disease without any ongoing therapy. Among those sustaining complete response at week 76, the mean UAS7 was 0.4, the mean Dermatology Life Quality Index (DLQI) was 1.17, and 83% had a DLQI of 0 or 1, indicating no meaningful impact of disease on quality of life. This off-treatment durability was observed despite confirmed clearance of barzolvolimab from circulation and normalization of serum tryptase — a mast cell biomarker — findings the study authors characterize as consistent with disease modification rather than symptom suppression alone, and which provide the scientific basis for the agent's ongoing phase 3 development.

In this segment of the video discussion on CSU management updates, Steve Dorman, MD, walks through the week 76 findings in detail, emphasizing that the persistence of complete response nearly 7 months after the last dose — in a population that entered the study with severe, long-standing disease — is not a pattern previously observed with any other agent in the CSU therapeutic landscape. The normalization of serum tryptase alongside the clearance of drug from circulation is a particularly important mechanistic signal, as it suggests that the disease-modifying effect is not dependent on ongoing drug exposure. Eric Karlin, MD, frames the DLQI outcomes as the patient-centered complement to the activity scores: an 83% rate of DLQI 0 or 1 at week 76 in patients who are no longer on therapy describes a population that has, by their own report, effectively returned to normal life.

Experts review REMIX-1/-2 pooled data on daily Urticaria Activity Score through day 7 and UCT progression through week 52, examining what daily resolution adds to the understanding of BTK inhibition onset and how the trajectory of disease control informs follow-up conversations with patients.

New Remibrutinib Data — Daily Disease Activity, Severity Band Shifts, and UCT Trajectory Through Week 52

Evaluating treatment response in chronic spontaneous urticaria has historically relied on the Urticaria Activity Score over 7 days (UAS7), a weekly composite of hive count and itch severity. Pooled data from the REMIX-1 and REMIX-2 phase 3 studies introduce a complementary daily UAS — derived from averaged morning and evening hive count and itch severity reports — that allows a more granular view of symptom trajectory from the first day of treatment. By day 7, mean daily UAS in the remibrutinib arm had fallen to 2.25, within the well-controlled threshold of less than 2.5, compared with 3.49 in the placebo group — a level consistent with moderate CSU symptoms. The categorical distribution shift is equally instructive: 37% of remibrutinib-treated patients had moved into the lowest UAS severity band by day 7, representing no or minimal symptoms, versus 9.7% on placebo. This means more than 1 in 3 patients on remibrutinib had achieved near-complete symptom resolution within the first week of treatment.

The REMIX data also capture the longer arc of disease control through the Urticaria Control Test (UCT), a validated patient-reported instrument with a well-controlled threshold of 12. At week 2, mean UCT in the remibrutinib arm was 10.5, compared with 7.3 in the placebo group — meaningfully improved but not yet at threshold. By week 12, mean UCT had risen to 11.4 in the remibrutinib group, approaching the well-controlled threshold closely. These improvements were sustained through week 52, and patients who crossed over from placebo to remibrutinib at week 24 achieved comparable UCT outcomes — reinforcing the consistency of the therapeutic effect regardless of when treatment was initiated. Together, the day-7 daily UAS data and the week-2 through week-52 UCT trajectory describe a therapy whose benefits are rapid in onset and durable over time.

In this segment of the video discussion on CSU management updates, Steve Dorman, MD, situates both data sets within the framework of patient communication. The day-7 daily UAS findings provide a concrete and evidence-supported basis for setting early expectations at the time of prescribing, while the UCT progression from week 2 through week 52 offers a practical scaffold for follow-up visits — a patient who has moved from a baseline UCT of 5 to 10.5 at week 2 has experienced a substantial transformation in disease burden even before crossing the formal well-controlled threshold, and framing that progress explicitly is an important part of sustaining engagement with therapy. Eric Karlin, MD, adds that capturing both UAS7 and UCT in practice gives the initiation and follow-up conversation a dual anchor — one instrument quantifying what the clinician observes and the other giving the patient's own experience a structured voice.

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In ‘Overcoming Barriers and Advancing Precision in Colorectal Cancer Screening,’ our experts delve into the ongoing challenges and future directions in colorectal cancer screening implementation. The discussion highlights persistent barriers to screening uptake, including access to care, follow-through after noninvasive testing, and disruptions caused by the COVID-19 pandemic. Faculty emphasize the value of patient navigation and mailed outreach programs in improving screening rates and closing care gaps. The conversation also examines how evolving technologies, including blood-based testing and machine learning–driven precision risk models, may reshape screening paradigms. Finally, the speakers consider the potential for risk-stratified approaches and evolving age recommendations as the field works toward more personalized and effective colorectal cancer prevention strategies.

Our next episode, ‘Individualizing When to Stop Colorectal Cancer Screening,’ features panelists discussing individualized decisions about when to stop colorectal cancer screening based on age, comorbidities, life expectancy, and patient preference, emphasizing shared decision-making, particularly for adults over 75 and those with limited life expectancy.

Learn how FIT, Cologuard, blood tests and colonoscopy compare on accuracy, follow-up timing, and easier prep options for screening.

Experts discuss the most clinically meaningful changes in the 2026 international urticaria guideline update, including the expanded step-up therapy framework and the current limitations of biomarkers in routine CSU practice.

CSU Management Updates: 2026 Guidelines and Latest Data

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Kichler notes that EPI is frequently overlooked in patients with symptoms resembling IBD or celiac disease and offers key insights on diagnosis and management.

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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.

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Latest News

Outcome Instruments in Practice and Baseline Underreporting in Untreated CSU

FDA Approves Setmelanotide (Imcivree) for Acquired Hypothalmic Obesity

Barzolvolimab Post-Treatment Durability —Off-Treatment Data, Complete Response Rates, and Quality-of-Life Outcomes

New Remibrutinib Data — Daily Disease Activity, Severity Band Shifts, and UCT Trajectory Through Week 52

Overcoming Barriers and Advancing Precision in Colorectal Cancer Screening