"Preventing itch-scratch cycle…Dupixent for prurigo nodularis"

Mechanism of inhibiting IL-4·IL13, targeting fundamental cause…reduces and improves itch

"Patients experience symptom improvement within three weeks…confirmed consistent effects in clinical trials and practices"

Changes are emerging in the treatment landscape for prurigo nodularis, a condition of patients with an itch so intense it persists until they bleed, destroying their lives.

With the introduction of the biologic 'Dupixent (dupilumab),' which targets the mechanism of the disease, there is a growing call for a reestablishment of treatment strategies, moving beyond the traditional symptom-focused approach.

Tae Young Han, a professor of dermatology at Nowon Eulji University Hospital

Tae Young Han, a professor of dermatology at Nowon Eulji University Hospital, said during a recent meeting with Daily Pharm, "Prurigo nodularis accompanies the most severe itch among all dermatologic conditions, significantly deteriorating quality of life of a patient," adding, "With the introduction of a targeted therapy, such as Dupixent, changes to the treatment paradigm is anticipated."

Prurigo nodularis is characterized by tens to hundreds of hard nodules accompanied by chronic, extreme itching. In over 80% of cases, the itch lasts more than six months, and for more than half, it persists for over two years. The psychological burden, including sleep disorders and depression, is so severe that quality of life is significantly compromised. 

The problem is the low awareness of the disease. It is often confused with atopic dermatitis, leading to diagnostic seeking where the correct diagnosis is significantly delayed. Missing the optimal treatment window can lead to chronicity and an increased risk of comorbidities.

The mechanism of the disease differs from simple skin conditions. The key is a Type 2 inflammatory response where the immune and nervous systems interact. Interleukins such as IL-4, IL-13, and IL-31 trigger and amplify the itch, forming a vicious cycle.

​ Sanofi’s Dupixent, developed based on this pathological mechanism, has emerged.

Dupixent inhibits both IL-4 and IL-13 signals. This approach blocks the root cause of the disease rather than merely alleviating inflammation. It reduces itch, leading to decreased scratching and eventual improvement in skin lesions.

Global clinical trials showed that the proportion of patients achieving significant itch reduction (WI-NRS reduction of 4 points) was approximately 3 times higher with Dupixent than with placebo, with rapid improvement starting in week 3. By week 24, the proportion of patients achieving clear or almost clear skin was significantly higher than that of the control group.

Professor Han stated: "While existing treatments only non-specifically suppress inflammation, Dupixent is significant in that it directly inhibits the key cytokines of Type 2 inflammation to reach the root cause," and that "Reducing the itch leads to less scratching, which eventually improves the lesions."

Q. How severe is the itch and the resulting decrease in quality of life?

The most prominent feature is the itch's extreme intensity. The scale of itch is evaluated with the WI-NRS (0–10 scale): 0 means no pruritus and 10 means very severe pruritus.

Many patients score 8 or higher, indicating very severe itch. Patients often describe not just itching, but stinging, pain, and a stabbing sensation.

In terms of the DLQI (Dermatology Life Quality Index), prurigo nodularis patients experience a much greater decline in quality of life than even psoriasis patients. 

Many suffer from anxiety, depression, and sleep disorders. Some patients even express suicidal ideation, saying they "want to die because it itches so much."

Q. How is the current treatment carried out?

Previously, there were no treatments directly targeting the Type 2 inflammatory response. We typically start with topical steroid ointments. If the nodules are too firm so that ointments cannot be absorbed, direct steroid injections are made into the nodules. 

If the nodules are too numerous, phototherapy is used, and if that is insufficient, immunosuppressants are used.

However, many patients are elderly (60s–80s), making these treatments difficult. Phototherapy requires standing naked in a closed booth for several minutes, which is a burden.

Immunosuppressants carry risks for patients with decreased kidney function or a history of cancer. Consequently, treatment is often limited to ointments, making it hard to achieve a sufficient response.

Under international guidelines (IFSI, US, and EU), biologics like Dupixent are recommended immediately if phototherapy or immunosuppressants are difficult to apply. In fact, biologics are considered the most effective options.

Q. What is the clinical value of Dupixent compared to existing treatments?

While conventional treatments focus on nonspecifically controlling overall inflammation, Dupixent differs mechanistically by directly inhibiting IL-4 and IL-13, the primary mediators of Type 2 inflammation, which is the core mechanism underlying the development of prurigo nodularis. By addressing the underlying cause of the disease, Dupixent approaches the condition at its root.

Because Dupixent targets the fundamental cause to effectively reduce itching, the natural result of decreased pruritus is reduced scratching behavior, which subsequently improves skin lesions. When these immunological abnormalities are controlled, it is possible to break the itch-scratch cycle that forms between the nervous system and the inflammatory response.

Furthermore, Dupixent has a robust safety profile from other indications. 

In fact, prurigo nodularis is strongly associated with repetitive scratching. Some patients even present with both atopic dermatitis and prurigo nodularis, as severe scratching from atopic dermatitis can progress to similar lesions. For such patients, including the elderly or those with underlying medical conditions, Dupixent can be used with relatively little burden, as it holds multiple indications for conditions such as atopic dermatitis, asthma, and chronic rhinosinusitis. 

Q. What improvements, in terms of patient symptoms, are seen after Dupixent treatment?

Clinical studies report a rapid reduction in itching within three weeks of starting treatment. In actual clinical practice, significant relief of pruritus is observed within three to four weeks, leading to a noticeable improvement in the patient’s quality of life. In particular, it serves as a critical treatment option for patients who find it difficult to use immunosuppressants due to medical histories such as hepatitis, dialysis, or tumors.

The administration protocol is specified as a continuous cycle every two weeks. By breaking the vicious itch-scratch cycle, Dupixent reduces scratching and improves skin lesions. Once this fundamental cycle is broken, cases have been observed in which the improved condition is maintained even after treatment is discontinued.

Q. Would you like to provide advice for patients with prurigo nodularis and for medical staff treating them?

Because the name prurigo nodularis is unfamiliar, many patients don't recognize their condition. Patients who do not seek dermatology often mistake their symptoms for simple eczema, being left without a correct diagnosis. They often wander between clinics. If a patient gets an accurate diagnosis from a dermatologist, symptoms can be improved. My advice is that with the emergence of new options such as biologics, patients should pursue treatment.