SDPA Poster Reports Positive Phase 3 Results of Dupilumab for PN

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When compared with placebo, dupilumab improved itch and skin lesions in both atopic and non-atopic prurigo nodularis (PN), according to a poster presented at the 2024 Society for Dermatology Physician Assistants Annual Dermatology Summer Conference.¹

The poster by Brian S. Kim, MD, MTR, FAAD, vice chair of research in the department of dermatology at the Icahn School of Medicine at Mount Sinai and director of the Mark Lebwohl Center for Neuroinflammation and Sensation, and colleagues reported on results from LIBERTY-PN PRIME (NCT04183335) and PRIME 2 (NCT04202679), both of which are phase 3 trials of dupilumab for the treatment of PN.2,3 Participants included adult patients between 18 and 80 years with PN whose disease was not adequately controlled by topical medications or for those in which those therapies were contraindicated. The study groups were divided into atopic and non-atopic disease; to be included in the atopic disease group, participants must have had a history of atopic comorbidities (eg, atopic dermatitis, allergic rhinitis/rhinoconjunctivits, asthma, or food allergy) or a current diagnosis of at least 1 atopic comorbidity. All participants were randomized to receive either dupilumab 300 mg or placebo every 2 weeks for 24 weeks.

Patients across the 4 groups (atopic + placebo [N=68]; atopic + dupilumab [N=67]; nonatopic + placebo [90]; nonatopic + dupilumab [N=86]) were similarly aged (about 50 years old), and weight was similar across the groups. About half of the patients among all 4 groups were White; Asian was the second most common race. Skin pain at baseline as measured by the Worst Itch Numerical Rating Scale (WI-NRS) were similar for all groups; skin pain NRS scores ranged from 6.9 to 7.5. About one-quarter to one-third of patients had Investigator's Global Assessment PN-Stage (IGA PN-S) of 4; 62% to 74% had IGA-PNS of 3 at baseline.

To determine efficacy of dupilumab for patients with PN regardless of atopic status, Kim et al were looking at the proportion of participants with: at least a 4 point reduction in the WI-NRS, an IGA PN-S score of 0 or 1, and with concomitant 4 point minimum WI-NRS reduction and IGA PN-S score of 0 or 1 at the midway (12 weeks) and endpoint of the study (24 weeks).

Kim and colleagues found dupilumab proved to be efficacious in both the atopic and nonatopic groups by achieving at least a 4-point improvement from baseline in WI‑NRS at 12 and 24 weeks of treatment (p = 0.0012 and p < 0.0001, respectively, for atopic and p = 0.0072 and p < 0.0001, respectively, for the nonatopic group). Dupilumab also showed statistically significant improvement in patients achieving an IGA PN‑S score of 0 or 1 at 12 weeks and 24 weeks for the atopic (p = 0.0008 and p < 0.0001, respectively) and nonatopic (p = 0.0596 and p = 0.0005, respectively). At 24 weeks, dupilumab was effective on both improvement in IGA PN-S and WI-NRS across both the atopic and nonatopic groups (P = 0.0057 and P = 0.007, respectively).

Overall, the researchers noted dupilumab’s safety profile in this study was comparable with its known safety profile. Treatment-related adverse events occurred at similar rates in patients treated with dupilumab in both the atopic and nonatopic groups (66.7% and 61.6%, respectively) compared with placebo across the atopic and nonatopic groups (52.9% and 59.6%, respectively).

Nearly half of all adult patients diagnosed with PN have either a history of atopic disease or have current comorbid atopic disease, Kim et al noted.

“These observations suggest that interleukin-4 receptor alpha (IL-4Rα) signaling is involved in PN regardless of patient history of atopic comorbidities,” Kim and colleagues concluded.

References

1. Kim BS, Gonçalo M, Ugajin T, et al. Dupilumab is Efficacious in Patients With Prurigo Nodularis Regardless of Atopic Comorbidities: Pooled Results From Two Phase 3 Trials (LIBERTY-PN PRIME and PRIME2). Poster presented at 2024 SDPA Annual Summer Dermatology Conference; June 5 -9; San Diego, California.

2. Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (LIBERTY-PN PRIME). ClinicalTrials.gov identifier: NCT04183335. Updated December 12, 2022. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT04183335

3. Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2). ClinicalTrials.gov identifier: NCT04202679. Updated December 12, 2022. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT04202679