Dupilumab improves multiple QoL parameters in patients with prurigo nodularis

Post hoc analyses using pooled data from the phase III LIBERTY-PN PRIME and PRIME2 trials showed that dupilumab improves disease-specific quality of life (QoL), itch, skin pain, and sleep in adult patients with prurigo nodularis.

The analyses evaluated 311 adults with prurigo nodularis that was inadequately controlled with topical treatments, or when such treatments are not advisable. They were randomized 1:1 to either dupilumab 300 mg Q2W (600 mg loading dose) or matching placebo for 24 weeks.

Disease-specific QoL

At baseline, the dupilumab and placebo arms had similar mean DLQI* total scores (18 and 17, respectively). “[These] scores correspond to a ‘very large’ impact of prurigo nodularis on QoL,” noted the investigators led by Dr Shawn Kwatra from the Johns Hopkins University School of Medicine, Baltimore, Maryland, US, at AAD 2023. “These patients had a high disease burden.”

About 5 percent of participants in both arms had a baseline DLQI score ≤5, which corresponded to ‘no’ to ‘small’ effect on QoL. At week 12, nearly half of dupilumab-treated patients have achieved a DLQI score ≤5, as opposed to only 34 percent in the placebo arm. By week 24, the rate in the dupilumab arm rose to 57 percent whereas for placebo, the rate dropped to 30 percent. [AAD 2023, abstract 42014]

The proportion of responders** was significantly higher with dupilumab vs placebo, both at week 12 (62.7 percent vs 27.8 percent) and week 24 (64.7 percent vs 22.8 percent; p<0.0001 for both).

Itch, skin pain, sleep

Participants had severe itch (WI-NRS*** 8.5), with a third of the overall cohort presenting with >100 nodules at baseline.

By week 24, the fraction of dupilumab-treated participants achieving within-patient meaningful improvement in WI-NRS 24 was more than thrice the rate observed in the placebo arm (58.8 percent vs 19.0 percent; p<0.0001). [AAD 2023, abstract 42275]

Similarly, dupilumab trumped placebo in terms of Skin Pain-NRS (49.7 percent vs 20.9 percent) and Sleep-NRS (42.5 percent vs 23.4 percent; p<0.0001 for both).

“The difference was significant starting at week 2 for WI-NRS and Sleep-NRS, and week 3 for Skin Pain-NRS,” said the researchers. For Skin Pain-NRS, although it lost statistical significance at week 6, this was regained by week 7 and sustained throughout the rest of the trial.

High symptom burden

In both analyses, the researchers noted that the safety profile of dupilumab was consistent with its known safety profile in its approved indications.

A chronic inflammatory skin disease characterized by the presence of itchy nodules on the trunk and extremities, prurigo nodularis is often accompanied by skin pain, sensations of stinging and burning, and sleep disruption, which severely impacts QoL. [J Am Acad Dermatol 2021;84:747-760; J Am Acad Dermatol 2020;83:1559-1565]

“[The lesions are] intensely pruritic … The high symptom burden in prurigo nodularis has been shown to impact QoL to a level similar to chronic systemic conditions such as stroke or diabetes mellitus,” said the investigators.

The current findings reflect the significant and clinically meaningful improvements in QoL, worst itch, skin pain, and sleep with dupilumab in this patient setting.