Could dupilumab put an end to the therapeutic draught in prurigo nodularis?

For patients with prurigo nodularis, dupilumab therapy led to significantly higher treatment success rates compared with placebo in terms of improved itch and disease stage in the phase 3 LIBERTY-PN PRIME 2 trial. The results also confirmed the known safety profile of dupilumab.

Prurigo nodularis (PN) is a chronic inflammatory disease characterised by hyperkeratotic nodules that appear particularly on the trunk and extremities [1]. To date, no treatments have been approved by the American or European medical agencies for this condition that has a pronounced negative influence on the quality of life [2,3]. As off-label therapies such as topicals, phototherapy, or systemic neuromodulators do not offer satisfactory disease control in many cases of moderate-to-severe PN, there is an unmet need for effective therapeutics [3–5].

The phase 3 LIBERTY-PN PRIME 2 study (NCT04202679) evaluated dupilumab for its efficacy on itch and lesion-healing in adult patients with pronounced PN [4]. The 160 randomised participants all suffered from ≥20 PN lesions and had been unsuccessfully treated with medium-to-very high potency topical corticosteroids. Of note, 38% of participants had more than 100 nodules. Baseline features of the study cohort included 64.4% women, with a mean age of 48.8 years, and a disease duration of 5.4 years. On a numerical rating scale (NRS), they presented a Worst Itch (WI-NRS) score of at least 7 (i.e. severe pruritus) in the week before the trial started. The mean WI-NRS score was 8.5, and 38.4% of participants presented an Investigator Global Assessment PN-Stage (IGA PN-S) score of 4.

The study treatment consisted of placebo or dupilumab with a loading dose of 600 mg, followed by 300 mg every 2 weeks until week 24 and a subsequent post-treatment monitoring of 12 weeks. The primary endpoint was the rate of participants experiencing a ≥4-point reduction in their WI-NRS score at week 12. Prof. Gil Yosipovitch (University of Miami, FL, USA) presented the results.

At 12 weeks, the results showed significant differences between placebo- and dupilumab-treated patients. The primary endpoint was reached by 37.2% in the dupilumab group and 22.0% in the placebo group (P=0.0216). Until week 24, the proportion with a ≥4-point improvement of WI-NRS score rose to 57.7% (P<0.0001 vs placebo). Another secondary endpoint, the achievement of IGA PN-S of 0/1 at week 24, was reached by 44.9% of participants on dupilumab versus 15.9% on placebo (P<0.0001).

Any kind of treatment-emerging adverse events were reported in 51.2% in the placebo and 57.1% in the dupilumab group. “The safety profile of dupilumab was consistent with the known safety profile in its approved indications,” Prof. Yosipovitch elaborated. No severe adverse events were seen. “I have lived all my life to see drugs that specifically treat itch – I think this result opens a lot of new opportunities for our patients.”

 

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   1. Huang AH, et al. J Am Acad Dermatol. 2020;83(6):1559–1565.
   2. Kwon CD, et al. Medicines (Basel). 2019;6(4):97.
   3. Elmariah S, et al. J Am Acad Dermatol. 2021;84(3):747–760.
   4. Yosipovitch G, et al. Dupilumab Significantly Improves Itch and Skin Lesions in Patients with Prurigo Nodularis: Results from a Phase 3 Trial (LIBERTY-PN PRIME2). S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.
   5. Qureshi AA, et al. J Am Acad Dermatol. 2019;80(3):756–764.

 

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Posted on 17 May, 202227 March, 2024