Nemolizumab

Interactions

Nemolizumab interacts in the following cases:

Vaccinations

It is recommended that patients complete all age-appropriate vaccinations in agreement with current immunisation guidelines prior to initiating treatment. Concurrent use of live vaccines in patients treated with nemolizumab should be avoided. It is unknown if administration of live vaccines during treatment will impact the safety or efficacy of these vaccines. No data are available on the response to non-live vaccines.

Asthma, current medical history of COPD and/or chronic bronchitis

Patients with an exacerbation of asthma requiring hospitalization in the preceding 12 months, patients with uncontrolled asthma during the preceding 3 months and patients with a current medical history of COPD and/or chronic bronchitis were excluded from clinical studies. No information on the efficacy or safety of nemolizumab in those patients is available.

Pregnancy

There is a limited amount of data on the use of nemolizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of nemolizumab during pregnancy.

Nursing mothers

No data are present on the excretion of nemolizumab in human milk. In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, which is decreasing to low concentrations soon afterwards. Consequently, transfer of IgG antibodies to the newborns through milk, may happen during the first few days. In this short period, a risk to the breastfed child cannot be excluded. Afterwards, nemolizumab could be used during breast-feeding if clinically needed.

Carcinogenesis, mutagenesis and fertility

Fertility

Animal studies showed no impairment of fertility.

Effects on ability to drive and use machines

Nemolizumab has no or negligible influence on the ability to drive and use machines.

Adverse reactions


Summary of the safety profile

The most common adverse reactions in atopic dermatitis and prurigo nodularis are type I hypersensitivity (1.1%; includes urticaria 1.0% and angioedema 0.1%) and injection site reactions (1.2%). Additional adverse reactions such as headache (7.0%), atopic dermatitis (4.6%), eczema (3.8%) and eczema nummular (3.5%) were reported in prurigo nodularis.

Tabulated list of adverse reactions

The table below includes all adverse reactions observed in clinical studies presented by system organ class and frequency, using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

List of adverse reactions:

MedDRA System
Organ Class
FrequencyAdverse reactions
Infections and
infestations
CommonSuperficial fungal infections#*
Blood and
lymphatic
system disorders
UncommonEosinophilia
Immune system
disorders
CommonType I hypersensitivity (incl. urticaria and
angioedema*)
Nervous system
disorders
CommonHeadache* (incl. tension headache)
Respiratory,
thoracic and
mediastinal
disorders
CommonWorsening of asthma* (incl. asthma, wheezing, peak
expiratory flow rate decreased)
Skin and
subcutaneous
tissue disorders
CommonAtopic dermatitis*,
Eczema*,
Eczema nummular*
General disorders
and administration
site conditions
CommonInjection site reactions (incl. erythema, pruritus,
haematoma, pain, irritation, bruising*, and injection
site oedema)

Occurred in atopic dermatitis studies
* Occurred in prurigo nodularis studies
# Superficial fungal infections include: body tinea, tinea pedis, onychomycosis, fungal infection, tinea versicolor, tinea cruris, fungal skin infection and fungal foot infection

Description of selected adverse reactions

Hypersensitivity

Type 1 hypersensitivity reactions (Ig-E mediated reactions), including mild urticaria and mild facial (peri-ocular) angioedema, were commonly observed in subjects treated with nemolizumab during the clinical studies. These reactions did not lead to treatment discontinuation.

Headache

In patients with prurigo nodularis, headache was more frequently reported in patients treated with nemolizumab (7.0%) compared to patients treated with placebo. Headache was more frequently observed in female patients in both groups. In the nemolizumab group, headache was mostly mild or moderate in severity and did not lead to discontinuation of treatment.

Worsening of asthma

In the PN patients with pre-existing asthma (n=51), 8 (15.7%) patients experienced a worsening of asthma (WOA) after initiation of nemolizumab, 5 of whom had a body weight >90 kg and received 60 mg nemolizumab every 4 weeks. In the population of PN patients with pre-existing asthma, WOA was 3 times more frequent in patients with a body weight >90 kg who received 60 mg nemolizumab every 4 weeks than in patients with a body weight <90 kg who received 30 mg nemolizumab every 4 weeks.

The majority of WOA events occurred within the first two months of treatment initiation and all were reported as mild or moderate in severity. Most patients experienced a single event of WOA during treatment and the event resolved with standard of care asthma medications (inhalers) without the use of systemic steroids. None led to permanent discontinuation of treatment. The incidence of WOA did not increase with longer term exposure to nemolizumab (up to Week 52) in the PN open-label long- term extension study.

Eczematous reactions

In patients with prurigo nodularis, eczematous reactions such as atopic dermatitis, eczema nummular or eczema were more frequently reported in nemolizumab-treated patients compared to patients treated with placebo: Atopic dermatitis (4.6%), eczema (3.8%) and eczema nummular (3.5%). These eczematous reactions were mild or moderate in severity. Atopic dermatitis led to nemolizumab discontinuation in 2 (0.5%) patients. Patients >65 years of age had a higher rate of eczematous reactions.

Eosinophilia

Proportion of patients with clinically significant elevated eosinophils (>700 cells/mcL) was 10,2% in the AD population (in the initial period) and 5,5% in the PN population. Severe eosinophilia (>5000 cells/mcL) was not observed in AD nemolizumab-treated patients in the initial treatment period. Adverse reactions of eosinophilia were reported in 0.2% of AD patients treated with nemolizumab during the initial treatment period up to Week 16. All events in AD subjects were mild in intensity and not associated with clinical symptoms. No TEAE of eosinophilia led to discontinuation of treatment. Apart from one case of eosinophilic colitis in an AD subject with other atopic comorbidities, there were no other reports of eosinophilic disorders.

Paediatric population

Atopic dermatitis

Adolescents (12 to 17 years of age)

The safety of nemolizumab was assessed in 176 paediatric subjects 12 to 17 years of age with moderate-to-severe atopic dermatitis enrolled in the ARCADIA 1 and ARCADIA 2 studies. The safety profile of nemolizumab in these subjects through Week 16 was similar to the safety profile seen in adults with atopic dermatitis.

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