乌鸦传媒

SAN DIEGO -- More than two-thirds of patients with prurigo nodularis obtained long-term relief from itching, skin lesions, and sleep disturbance with the interleukin (IL)-31 antagonist nemolizumab, according to the largest-ever trial in the disease.

After 52 weeks of continuous treatment, 88.9% of patients had a ≥4-point improvement in pruritus score, and 81.5% had a ≥4-point improvement in sleep disturbance. Improvement in skin lesions occurred in 69.2%, and 79.1% of patients had healing of >75% of pruriginous lesions.

Patients who switched from placebo to nemolizumab had 52-week outcomes similar to those of patients who received the drug continuously, reported Shawn G. Kwatra, MD, of the Johns Hopkins Itch Center in Baltimore, at the American Academy of Dermatology meeting.

"Ongoing improvements are seen in itch, skin lesions, sleep disturbance, and quality of life," said Kwatra. "Itch-free or nearly itch-free state is achieved in two-thirds of patients, and very clinically meaningful improvement in quality of life. Long-term safety data are consistent with previously reported safety data from phase III trials."

The drug has a couple of "new twists" that dermatologists will have to consider when treating patients, said Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland.

"This is a drug that can worsen asthma, but just how bad is it?" asked Blauvelt. "Is it something we should be worried about? I know the [reported frequency] is 3.7%, but still, that is not rare. The other issue is peripheral edema. Can you tell us what it looks like and how to manage it?"

The incidence of new-onset asthma is about 1% in patients treated with nemolizumab, said Kwatra. That compares with a rate of 0.6% in placebo-treated patients from randomized trials.

"So there really wasn't an imbalance in the number of cases," Kwatra continued. "We did have some patients with existing asthma, and we saw worsening of asthma in some of those patients. The worsening was intermittent and resolved in many cases, and a majority did not lead to any discontinuation."

Some cases of edema occurred in and around skin lesions, said Kwatra. Lower-extremity edema did occur in some patients but resolved during treatment in most cases.

One of the , prurigo nodularis causes severe itch in association with multiple nodular skin lesions. The condition quality of life and physical, emotional, and psychological well-being. Patients have few effective therapeutic options.

The neuroimmune cytokine IL-31 has a key role in regulation of itch and inflammation and contributes to keratinocyte hyperproliferation and fibrosis, said Kwatra. In the phase III OLYMPIA 1 and OLYMPIA 2 trials, nemolizumab led to significant improvement in itch and nodules, beginning as early as 4 weeks and continuing to 24 weeks.

Kwatra reported updated findings from the OLYMPIA research program, including 52-week follow-up data from an (OLE). The analysis included 508 patients: 307 treated with nemolizumab, 174 who crossed over from placebo to nemolizumab, and 27 patients who were retreated with the IL-31 inhibitor.

Key outcomes for the OLE included the proportion of patients who achieved and maintained a ≥4-point improvement in itch and sleep disturbance at week 52, Investigator Global Assessment (IGA) of 0/1 (clear/almost clear), >75% lesion healing, a ≥4-point improvement in the Dermatology Life Quality Index (DLQI), and mean DLQI to week 52.

The analysis focused on the 307 patents who received continuous nemolizumab and the 174 who switched to nemolizumab. The data showed that 88.8% of patients on continuous treatment had a ≥4-point improvement in itch at 28 weeks, and 88.9% had that improvement at 52 weeks. Patients who switched to nemolizumab quickly caught up, as 82.4% achieved a ≥4-point improvement in itch by week 28, increasing slightly to 83.3% at week 52.

The minimum 4-point improvement in weekly mean sleep disturbance was achieved by 75.4% of the continuous therapy group at 28 weeks and 75.7% of the crossover group. Rates at 52 weeks were 81.5% with continuous therapy and 79.2% for the crossover group.

After 52 weeks of follow-up, 69.2% of continuous-therapy patients had an IGA rating of 0/1, compared with 64.5% for the switch group. Also at 52 weeks, 79.1% of patients in both groups had >75% healing of lesions. Kwatra reported that 67.8% of continuous-therapy patients attained a weekly average Peak Pruritus Numerical Rating Scale <2, as did 64.4% of the patients who switched to nemolizumab. From 90-91% of patients in both groups had a least a 4-point improvement in the DLQI at 52 weeks.

The nemolizumab safety profile remained consistent with the findings after 24 weeks.

Drugmaker Galderma recently announced that it has to FDA seeking approval for nemolizumab as a treatment for prurigo nodularis and atopic dermatitis.

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