Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Almirall, S.A., Ronda General Mitre, 151, 08022 Barcelona, Spain
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
If a systemic hypersensitivity reaction (immediate or delayed) occurs, administration of lebrikizumab should be discontinued and appropriate therapy initiated.
Patients treated with lebrikizumab who develop conjunctivitis that does not resolve following standard treatment should undergo ophthalmological examination (see section 4.8).
Patients with known helminth infections were excluded from participation in clinical studies. It is unknown if lebrikizumab will influence the immune response against helminth infections by inhibiting IL-13 signalling.
Patients with pre-existing helminth infections should be treated before initiating treatment with lebrikizumab. If patients become infected while receiving lebrikizumab and do not respond to antihelminth treatment, treatment with lebrikizumab should be discontinued until infection resolves.
Prior to initiating therapy with lebrikizumab, it is recommended that patients are brought up to date with all age-appropriate immunisations according to current immunisation guidelines. Live and live attenuated vaccines should not be given concurrently with lebrikizumab as clinical safety and efficacy has not been established. Immune responses to non-live vaccines were assessed in a combined tetanus, diphtheria and acellular pertussis vaccine (TdaP) and a meningococcal polysaccharide vaccine (see section 4.5).
No interaction studies have been performed.
The safety and efficacy of concurrent use of lebrikizumab with live and live attenuated vaccines has not been studied. Live and live attenuated vaccines should not be given concurrently with lebrikizumab.
Immune responses to non-live vaccines were assessed in a study in which adult patients with atopic dermatitis were treated with lebrikizumab 500 mg at weeks 0 and 2 followed by lebrikizumab 250 mg every other week. After 12 weeks of lebrikizumab administration, patients were vaccinated with a combined tetanus, diphtheria, and acellular pertussis vaccine TdaP vaccine (T cell-dependent) and a meningococcal polysaccharide vaccine (T cell-independent) and immune responses were assessed 4 weeks later. Antibody responses to both non-live vaccines were not negatively impacted by the concomitant lebrikizumab treatment. No adverse interactions between the non-live vaccines and lebrikizumab were noted in the study. Therefore, patients receiving lebrikizumab may receive concurrent inactivated or non-live vaccinations. For information on live vaccines see section 4.4.
Given that lebrikizumab is a monoclonal antibody, no pharmacokinetic interactions are expected.
There are limited amount of data from the use of lebrikizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of lebrikizumab during pregnancy.
It is unknown whether lebrikizumab is excreted in human milk or absorbed systemically after ingestion. Maternal IgG is known to be present in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue from lebrikizumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Animal studies showed no impairment of fertility (see section 5.3).
Lebrikizumab has no or negligible influence on the ability to drive and use machines.
The most common adverse reactions are conjunctivitis (6.9%), injection site reactions (2.6%), conjunctivitis allergic (1.8%) and dry eye (1.4%).
Across all clinical studies in atopic dermatitis, a total of 1720 patients were administered lebrikizumab, of which, 891 patients were exposed to lebrikizumab for at least one year. Unless otherwise stated, the frequencies are based on a pool of 4 randomised, double-blind studies in patients with moderate-tosevere atopic dermatitis where 783 patients were treated with subcutaneous lebrikizumab during the placebo-controlled period (first 16 weeks of treatment).
Listed in Table 1 are adverse reactions observed from clinical trials 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).
Table 1. List of adverse reactions:
| MedDRA System Organ Class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | Common | Conjunctivitis |
| Uncommon | Herpes zoster | |
| Blood and lymphatic system disorders | Uncommon | Eosinophilia |
| Eye disorders | Common | Conjunctivitis allergic Dry eye |
| Uncommon | Keratitis Blepharitis | |
| General disorders and administration site conditions | Common | Injection site reaction |
During the first 16 weeks of treatment conjunctivitis, conjunctivitis allergic, blepharitis and keratitis were reported more frequently in patients treated with lebrikizumab (6.9%, 1.8%, 0.8% and 0.6% respectively) compared to placebo (1.8%, 0.7%, 0.2% and 0.3%).
During maintenance treatment period (16-52 weeks) the incidence of conjunctivitis and conjunctivitis allergic with lebrikizumab was 5.0% and 5.9% respectively.
Across all clinical studies, among lebrikizumab-treated patients treatment discontinuation due to conjunctivitis and conjunctivitis allergic occurred in 0.7% and 0.3% of cases, respectively. Severe cases of conjunctivitis and conjunctivitis allergic occurred in 0.1% and 0.2% of cases, respectively. 72% of patients recovered, of those 57% recovered within 90 days.
Lebrikizumab-treated patients had a greater mean increase from baseline in eosinophil count compared to patients treated with placebo. In lebrikizumab treated patients 20.3% had any increase in eosinophil count compared to 11.7% with placebo. In general, the increase in the lebrikizumab-treated patients was mild or moderate and transient. Eosinophilia >5000 cells/mcL was observed in 0.4% lebrikizumab-treated patients and none of the placebo-treated patients. Adverse reactions of eosinophilia were reported in 0.6% of patients treated with lebrikizumab and with a similar rate in patients treated with placebo during the initial treatment period. Eosinophilia did not result in treatment discontinuation and no eosinophil-related disorders were reported.
Injection site reactions (including pain and erythema) were reported more frequently in patients who received lebrikizumab (2.6%) compared to placebo (1.5%). The majority (95%) of injection site reactions were mild or moderate in severity, and few patients (<0.5%) discontinued lebrikizumab treatment.
Herpes zoster was reported in 0.6% of the patients treated with lebrikizumab and none of the patients in the placebo group. All herpes zoster events reported were mild or moderate in severity and none led to permanent discontinuation of treatment.
The long-term safety of lebrikizumab was assessed in 5 clinical studies. In the two monotherapy studies (ADvocate-1, ADvocate-2) up to 52 weeks and in patients enrolled in the TCS combination therapy study (ADhere) and followed in a long-term extension study (ADjoin) for a total of 56 weeks and the monotherapy ADore study in adolescents for also up to 52 weeks. The safety profile of lebrikizumab as monotherapy through week 52 or in combination with TCS through week 56 is consistent with the safety profile observed up to week 16.
The safety of lebrikizumab was assessed in 372 patients 12 to 17 years of age with moderate-to-severe atopic dermatitis, including 270 patients exposed for at least one year. The safety profile of lebrikizumab in these patients was similar to the safety profile in adults with atopic dermatitis.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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