"CHE, limitations of steroids…attention is now focused on 'Anzupgo'"

Patients undergo repeated treatment despite ineffective treatments…"must be transitioned at the right clinical window"

Has secured long-term data at 52 week…provided evidence for improving skin barrier

In the treatment of chronic hand eczema (CHE), treatment strategies are shifting toward to match individual patient conditions, moving away from the  repeated topical corticosteroid (TCS) use.

With the introduction of LEO Pharma's 'Anzupgo (delgocitinib),' a non-steroidal topical pan-Janus kinase (JAK) inhibitor, clinical experts evaluate that a viable therapeutic option for use before advancing to systemic therapy is now available.

Professor Margitta Worm, Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Germany

During a meeting with DailyPharm, Professor Margitta Worm emphasized the critical importance of "timely intervention" in treating chronic hand eczema.

Professor Worm explained that rather than cycling through ineffective topical corticosteroid treatments, shifting the therapeutic strategy at the right clinical window based on the patient's disease severity is essential to mitigating long-term disease progression and functional decline.

Chronic hand eczema (CHE) is a chronic inflammatory skin condition characterized by itching and pain. It causes a heavy socioeconomic burden, including absenteeism, reduced productivity, impaired hand function, occupational limitations, and diminished quality of life (QoL).  

Because the hands are the most actively utilized body parts in both daily routines and professional activities, persistent symptoms disrupt work performance, interpersonal relationships, and general daily living. The disease burden is particularly pronounced among professions that require repetitive hand use, such as healthcare professionals, hairdressers, chefs, and manufacturing workers, often making career retention difficult.  

In real-world clinical practice, we often see identical TCS regimens repeated or to delay transitions to systemic therapy, even for patients who fail to respond adequately to initial topical corticosteroids. This therapeutic delays is cited as a major driver of chronic disease persistence and relapses. Consequently, "timely treatment," modifying the therapeutic strategy at the optimal juncture, is emerging as a new core management principle.

The topical JAK inhibitor Anzupgo is leading the shift in the therapeutic landscape. Anzupgo cream was developed for use across various clinical subtypes of chronic hand eczema by targeting the JAK-STAT signaling pathway to modulate multiple inflammatory cytokines, rather than suppressing a single pathway.

In the global Phase 3 DELTA 1 and DELTA 2 clinical trials, one in two patients achieved a 75% or greater improvement in symptoms (HECSI-75) after 16 weeks of treatment. The long-term efficacy and safety profiles were further validated in the DELTA 3 open-label extension study, which followed patients for up to 52 weeks.  

Furthermore, the investigator-initiated trial (IIT) known as the 'Del-Bi study' demonstrated upregulation of key structural proteins responsible for maintaining the skin barrier. This has drawn significant industry attention to the drug's potential for restoring the skin barrier beyond simple symptomatic relief.

Professor Worm emphasized, "A substantial number of chronic hand eczema patients miss the optimal therapeutic window by repeatedly relying on topical corticosteroids when they actually require stepped-up therapy. If initial efficacy is inadequate, clinicians should pivot the therapeutic strategy promptly rather than waiting, thereby preventing long-term disease exacerbation and deterioration of the patient's quality of life."

Q.Delayed treatment remain the primary issue  in chronic hand eczema management. 

Delayed diagnosis and treatment are currently recognized as critical clinical challenges in CHE. A Danish cohort study involving approximately 4,000 patients found that a significant proportion of patients with chronic hand eczema experience prolonged delays before initiating systemic therapy.

Notably, approximately 44% of the total patients required more than 8 years to reach their first systemic treatment line. While clinical timelines vary by patient severity, these findings suggest that at least 50% of moderate-to-severe CHE patients are essentially candidates for immediate transition to stepped-up therapy.

During these periods of delayed treatment, patients typically undergo multiple cycles of repeated topical corticosteroid (TCS) applications. While TCS remains the foundational first-line therapy for chronic hand eczema, there is a distinct clinical tendency to cycle through identical or similar TCS regimens repeatedly without transitioning to higher-tier therapies at the appropriate time aligned with disease severity.

Q. Given the disease burden of CHE, what is the clinical significance of having this new therapeutic option available?

Chronic hand eczema severely impacts a patient's life. It not only disturbs individual daily routines but also compromises overall workplace operational capabilities, while severe pain and pruritus significantly degrade health-related quality of life (HRQoL).  

If adequate therapy is not initiated promptly, the condition inevitably worsens over time. Crucially, the affected patient group is not confined to the elderly but includes a significant proportion of the young and working-age population. In these cases, the negative impact reverberates across individual labor capacity, career longevity, and the broader macroeconomic landscape, translating into a societal economic burden driven by absenteeism and lost productivity.  

Chronic hand eczema absolutely demands appropriate therapeutic intervention, and fortunately, dedicated treatments are now available. With the advent of novel therapeutics driven by innovative R&D, it is vital to actively leverage these safer, more effective clinical options for patients.  

Existing topical corticosteroids carry risks of adverse events that can paradoxically worsen the patient's skin condition over the long term, particularly by further degrading the critical skin barrier function. In this regard, a novel alternative was a highly anticipated clinical unmet need.  

Q. What changes have been brought to the CHE treatment landscape since the introduction of Anzupgo cream?

The emergence of a novel topical agent capable of controlling the disease while reducing dependence on topical corticosteroids (TCS) represents a significant paradigm shift in the treatment landscape of chronic hand eczema.

Previously, the standard clinical pathway was to transition directly to systemic therapies if symptoms remained uncontrolled despite TCS use. Now, clinicians have an additional, highly effective topical option to use before that escalation step. Consequently, this provides a new clinical window to pursue a safer, more effective treatment before deploying systemic regimens, thereby curbing the overreliance on topical corticosteroids.

Q. What are the reasons for Anzupgo cream to be applicable across diverse clinical subtypes, and what are its key clinical advantages?

A clinical strength of this agent is its excellent local tolerability. Both in clinical trials and real-world experience, adverse events related to local skin irritation were rarely reported, demonstrating a highly favorable local tolerability profile. This encourages high patient compliance and supports long-term adherence without treatment resistance or aversion.  

Another critical differentiator is its rapid onset of action and sustained long-term efficacy. Pruritus, a hallmark symptom that severely compromises patient quality of life, demonstrates marked improvement as early as Day 1 of application. Statistically significant reductions in pain are also observed within days of initiation, specifically by Day 3 in clinical trials.  

Clinical data show that this rapid initial efficacy and disease control are overall sustained in long-term studies extending up to 1 year (approximately 52 weeks). This swift symptomatic relief, combined with durable efficacy, directly drives high patient satisfaction and encourages treatment persistence.  

While some patients respond well and experience delayed recurrence even after temporary discontinuation, others experience a relatively rapid return of symptoms post-cessation. For the latter group who experience swift recurrence, long-term maintenance therapy can be evaluated based on the 52-week long-term safety and efficacy data established in the DELTA 3 study.

Q. Could you elaborate on the background, key findings, and clinical implications of the 'Del-Bi study,' an investigator-initiated trial (IIT)?

The Del-Bi study was specifically designed to evaluate whether Anzupgo cream triggers downstream physiological changes within the skin barrier beyond superficial symptom suppression. The trial enrolled active, working-age patients with chronic hand eczema, with a mean age of approximately 43.

Following a 12-week treatment regimen, skin tissue biopsies revealed a statistically significant upregulation of key structural proteins essential for maintaining the skin barrier compared with baseline. ​These findings suggest that Anzupgo cream goes beyond simply resolving visible lesions; it actively contributes to the structural repair and restoration of the damaged skin barrier. This can potentially mitigate the penetration of external irritants and lower the risk of subsequent inflammatory flares, providing meaningful clinical evidence for stable, long-term disease management.  

Q. What are the key advantages of Anzupgo cream that clinicians can anticipate in real-world practice?

Even with topical formulations, there are often clinical apprehensions regarding systemic drug absorption leading to systemic exposure issues. However, even in the 52-week long-term extension study, Anzupgo cream did not exhibit clinically significant or elevated systemic concentrations in blood samples.

Consequently, there is no need for routine blood monitoring or laboratory testing, which is a significant advantage for both patients and healthcare providers. From a patient convenience standpoint, this agent alleviates the burden of unnecessary diagnostic testing, while also positively impacting healthcare economics by reducing ancillary medical expenditures. 

Furthermore, in terms of clinical efficacy, Anzupgo cream demonstrated consistent therapeutic outcomes across the various chronic hand eczema subtypes. This uniform efficacy represents a major practical advantage in real-world settings, allowing clinicians to use the treatment broadly without having to strictly categorize patients into rigid clinical subgroups. Overall, the successful development and availability of such an innovative therapeutic agent is highly encouraging,