番茄社区

Dupilumab (Dupixent) improved itch and skin lesions compared with placebo in people with prurigo nodularis (PN), according to a study in .

The data, from a pair of phase 3 trials known as LIBERTY-PN PRIME and PRIME 2, came from adults with PN who had ≥20 nodules and severe itch that had not been adequately controlled by topical therapies. Patients were randomized 1:1 to 300 mg of dupilumab or placebo subcutaneously every 2 weeks for 24 weeks.

Patients in both trials saw meaningful improvements after taking dupilumab. A ≥4-point reduction in the Worst Itch Numeric Rating Scale or WI-NRS occurred at week 24 in 60.0% of patients in the dupilumab arm and in 18.4% in the placebo arm in the PRIME trial (95% CI 27.8-57.7 for the difference, P<0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI 2.3-31.2; P=0.022). Safety was consistent with the known dupilumab safety profile.

Co-author Ariane Dubost-Brama, MD, is clinical research director of dupilumab for Sanofi, which funded the study and jointly developed dupilumab. Her exchange with the Reading Room has been edited for length and clarity.

What was the key purpose of this investigation?

Dubost-Brama: PN is frequently inadequately controlled with topical treatments. Although systemic treatments including neuromodulators or immunosuppressive agents are commonly used off-label, their efficacy and safety have not been demonstrated in well controlled clinical trials.

Dupilumab is a fully human monoclonal antibody that inhibits the IL-4 and IL-13 pathways. Dupilumab is currently approved in the U.S., Europe, Japan, and other countries for use in certain patients with moderate-to-severe atopic dermatitis and asthma, among other conditions.

The PRIME and PRIME 2 studies were designed to address this important gap and establish the efficacy and safety of dupilumab in PN in a robust manner.

How would you summarize your primary findings?

Dubost-Brama: These two replicate studies demonstrate that dupilumab provides meaningful improvement to patients with uncontrolled moderate to severe PN, significantly reducing both the severe itch and the extensive skin lesions that were refractory to prior treatments, in comparison to placebo.

After 6 months of treatment with dupilumab, a significant proportion of patients achieved clear or almost clear skin and fewer required other rescue treatments. Treatment also led to significant improvements in quality of life and improvements in mental health measures in these patients. In addition, dupilumab was well tolerated in patients with PN, consistent with its known safety profile.

What are the most important take-home messages?

Dubost-Brama: Patients with moderate-to-severe PN that is not controlled by topical treatments can benefit from dupilumab, with or without topical corticosteroids and/or topical calcineurin inhibitors and irrespective of their atopic or non-atopic background.

By targeting two key and central drivers of the type 2 pathway and potentially interfering with the itch-scratch cycle, dupilumab represents a novel treatment paradigm for PN that not only treats the entire spectrum of its clinical manifestations, including pruritus, skin pain, and skin lesions, but also improves quality of life. Dupilumab also lowers the need for rescue treatment for PN.

What does the foreseeable future hold for dupilumab and dupilumab research?

Dubost-Brama: These studies were conducted in adults with PN. The potential use of dupilumab in children with PN will be also investigated.

In addition, we are continuing our investigation of dupilumab in other chronic skin conditions, including its safety and efficacy in patients with chronic pruritus of unknown origin () -- another chronic itch disease observed most commonly in the elderly population -- and bullous pemphigoid ().