Spesolimab

The safety and efficacy of spesolimab in combination with immunosuppressants, including biologics, have not been evaluated systematically. In the GPP flare treatment clinical study, there was a washout period for most other treatments (biologics, other systemic immunomodulating treatments), while some treatments were discontinued before initiation of spesolimab treatment with no washout period required (methotrexate, cyclosporine, retinoids, topical treatments).

Concomitant use of other immunosuppressants and spesolimab is not recommended. At initiation of spesolimab treatment, other GPP treatments should be stopped and other treatments (e.g. with systemic immunosuppressants) should not be used concomitantly to treat the flare.

In patients with a chronic infection or a history of recurrent infection, the potential risks and expected clinical benefits of treatment should be considered prior to prescribing spesolimab.

There are no or limited data from the use of spesolimab in pregnant women. Non-clinical studies using a surrogate, mouse specific anti-IL36R monoclonal antibody do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Human immunoglobulin (IgG) is known to cross the placental barrier. As a precautionary measure, it is preferable to avoid the use of spesolimab during pregnancy.

No data are present on excretion of spesolimab 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, spesolimab can be used during breastfeeding if clinically needed. If treatment was discontinued before the last trimester of pregnancy, breastfeeding can be started immediately after birth.

Fertility

There are no data available on the effect of spesolimab on human fertility. Studies in mice using a surrogate, mouse specific anti-IL36R monoclonal antibody, do not indicate direct or indirect harmful effects with respect to fertility from antagonism of IL36R.

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

Summary of the safety profile

The most frequently reported adverse reactions are infections (17.1%) with urinary tract infection reported as serious in 1 patient (2.9%) (see Description of selected adverse reactions).

Tabulated list of adverse reactions

The table below provides a list of the adverse reactions reported from clinical trials. The adverse reactions are listed by MedDRA System Organ Class (SOC) and frequency category using the following convention: 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), not known (frequency cannot be estimated from the available data).

Adverse reactions:

^a The most commonly reported infections were Urinary tract infection (Common) and Upper respiratory tract infection (Common)
^b Not reported in Effisayil 1

Description of selected adverse reactions

Infections

During the 1-week placebo-controlled period in Effisayil 1, infections were reported in 17.1% of patients treated with spesolimab compared with 5.6% of patients treated with placebo. In Effisayil 1, serious infection (urinary tract infection) was reported in 1 patient (2.9%) in the spesolimab group and no patient in the placebo group. During the placebo-controlled period of up to 48 weeks in Effisayil 2, infections were reported in 33.3% of patients treated with spesolimab and 33.3% of patients treated with placebo. In Effisayil 2, serious infections were reported in 3 patients (3.2%) in the spesolimab group and no patient in the placebo group.

Infections observed in clinical trials with spesolimab were generally mild to moderate with no distinct pattern regarding pathogen or type of infection.

Injection site reactions

Injection site reactions include erythema, swelling, pain, induration, warmth, exfoliation, papule, pruritus, rash, and urticaria at the injection site. Injection site reactions were typically mild to moderate in severity.

Paediatric population

The available data for adolescents are limited. 8 adolescent patients with GPP, 14 to 17 years of age, were enrolled in trial Effisayil 2. Overall, the safety profile in adolescents treated with spesolimab (n=6) was consistent with the safety profile in adults and no new safety concerns have been identified.