Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Summary of the safety profile

The most common adverse reactions are conjunctivitis (6.9%), injection site reactions (2.6%), conjunctivitis allergic (1.8%) and dry eye (1.4%).

Tabulated list of adverse reactions

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-to- severe 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               Frequency                Adverse reaction Organ Class
Infections and              Common                   Conjunctivitis infestations                Uncommon                 Herpes zoster
Blood and lymphatic         Uncommon                 Eosinophilia system disorders
Eye disorders               Common                   Conjunctivitis allergic Dry eye
Uncommon                 Keratitis
Blepharitis

General disorders and      Common                   Injection site reaction administration site conditions

Description of selected adverse reactions

Conjunctivitis and related events
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.

Eosinophilia

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

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

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.

Long term safety

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.



Paediatric population

Adolescents 12 to 17 years of age
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 of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il