Time is the answer: Dupilumab effectiveness in prurigo nodularis patients

Prurigo nodularis (PN) is a highly impactful skin condition, frequently occurring in the context of older patients with comorbidities. In this setting, identifying effective, safe and long-lasting treatments has been a topic of active discussion amongst clinicians.¹ Very few licenced medications are currently available to alleviate patients' clinical manifestations and to improve symptoms of high impact such as itch and sleep disturbance.

This issue of the Journal contains a further valuable contribution to this discussion by Chiricozzi and colleagues, who present their real-world experience in Italy of the long-term response to dupilumab for this indication. The authors present a series of 64 patients, half of whom have been followed up for almost 2 years, whose life has been transformed by a beneficial long-term use of dupilumab for PN.²

Prior to receiving this medication, most patients received a plethora of other systemic treatments, including phototherapy, systemic steroids (50 patients), ciclosporin (31 patients) and methotrexate (four patients), which had all been discontinued either because of inefficacy or side effects. While the authors do not mention on the length of treatment on the aforementioned immunosuppressants, it is reasonable to postulate that it would have been relatively short, since only methotrexate is commonly used beyond 52 weeks because of well-known side effects of oral steroids and ciclosporin.

Data on effectiveness and safety of dupilumab in PN is well-established and extensively described.³ However, several reported aspects of real-world experience addressed in this letter provide new insights into the appropriate management of these patients.

In this cohort, patients without an atopic diathesis and normal IgE respond less quickly to the given medication, but went on to achieve a IGA CPNs 0–1 (Investigator global assessment [IGA]—CPN) at 52 weeks. Thus, when commencing dupilumab in the setting of PN patients with no atopic background, and a normal IgE at baseline, pre-treatment counselling should include informing the patient of the possibility of a slower response to treatment. This observation will also provide clinicians with the confidence to continue treatment to 52 weeks, even when initial response is less impressive than one typically sees in the context of eczema.

The other important finding is the demonstrated progressive and sustained downtrend of patient-reported outcomes, such as itch severity (NRS itch), sleep deprivation (NRS sleep) and quality of life (DLQI) scores, far beyond the 16 weeks required by NICE for continuation of the given medication. Again, this will allow clinicians to be optimistic with their patients about the likelihood of continuing improvement beyond 16 weeks.

Dupilumab has been demonstrated to have an excellent safety profile, with no known organ specific toxicity to liver or kidney, and no risk of reactivations of latent infections such as hepatitis and tuberculosis.⁴ In this study, Chiricozzi et al provide further reassurance in this regard, with a low rate of adverse events in their cohort. It would have been interesting to know the rate of ocular complications in this Italian cohort—it has previously been reported that the incidence of conjunctivitis in PN patients treated with dupilumab is higher than that of atopic dermatitis patients treated with this drug.⁵

These new insights are precious and give further evidence that dupilumab is a highly effective therapeutic option in PN, and that patience is needed from both patient and clinician when expecting positive outcomes. Chronic skin conditions such as PN are deeply ingrained in body and mind; thus, it is perhaps not surprising that a longer than postulated time is needed for the negative effects to be reversed.

The author has no conflict of interest to declare.