Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Boehringer Ingelheim International GmbH, Binger Str. 173, 55216 Ingelheim am Rhein, Germany
Severe or life-threatening hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).
Clinically important active infections (e.g. active tuberculosis, see section 4.4).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Spesolimab may increase the risk of infections (see section 4.8).
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. Treatment with spesolimab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Patients should be instructed to seek medical advice if signs or symptoms of clinically important infection occur after treatment with spesolimab.
Prior to initiating treatment with spesolimab, patients should be evaluated for tuberculosis (TB) infection. Spesolimab is contraindicated to patients with active TB infection (see section 4.3).
Anti-TB therapy should be considered prior to initiating spesolimab treatment in patients with latent TB, a history of TB or possible previous exposure to people with active tuberculosis in whom an adequate course of treatment cannot be confirmed. After spesolimab treatment, patients should be monitored for signs and symptoms of active TB.
Hypersensitivity and infusion-related reactions may occur with monoclonal antibodies such as spesolimab. Hypersensitivity may include immediate reactions such as anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS).
If a patient develops signs of anaphylaxis or other serious hypersensitivity, spesolimab treatment should be discontinued immediately and appropriate treatment should be initiated (see section 4.3).
If a patient develops mild or moderate hypersensitivity during the infusion, treatment should be stopped and appropriate medical therapy should be considered (e.g., systemic anti-histamines and/or corticosteroids). Upon resolution of the reaction, the infusion may be restarted at a slower infusion rate with gradual increase to complete the infusion (see section 4.2).
There is no experience from the use of spesolimab in patients with an immediate, life-threatening flare of GPP or a flare requiring intensive care treatment.
The safety and efficacy of spesolimab in combination with immunosuppressants, including biologics, have not been evaluated systematically (see section 4.5). 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) (see section 5.1).
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.
Very limited efficacy and safety data are available for re-treatment with spesolimab for a subsequent new flare. Data are available for five patients with GPP who received re-treatment at a subsequent new flare and followed up for a minimum of 8 weeks.
It is unknown whether spesolimab affects the efficacy of vaccines.
No data are available on the potential secondary transmission of infection by live vaccines in patients receiving spesolimab (see section 4.5). The interval between live vaccinations and initiation of spesolimab therapy should be at least 4 weeks. Live vaccines should not be administered for at least 16 weeks after treatment with spesolimab.
The potential for peripheral neuropathy with spesolimab is unknown. Cases of peripheral neuropathy have been reported in clinical trials with spesolimab. Physicians should be vigilant for symptoms potentially indicative of new-onset peripheral neuropathy.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium free’.
No interaction studies have been performed. For the treatment of GPP flares, spesolimab is not expected to cause cytokine mediated CYP interaction as a perpetrator.
Live vaccines should not be given concurrently with spesolimab (see section 4.4).
There is limited experience from the use of spesolimab in combination with immunosuppressants in GPP patients (see section 4.4).
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 (see section 5.3). 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. When treatment has occurred up to the last few months of pregnancy, breastfeeding can be started immediately after birth.
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 (see section 5.3).
Spevigo has no or negligible influence on the ability to drive and use machines.
The most frequent adverse reactions are infections (17.1%) with urinary tract infection reported as serious in 1 patient (2.9%).
Table 1 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).
Table 1. Adverse reactions:
| System organ class | Adverse reactions | Frequencies |
|---|---|---|
| Infections and infestations | Infectiona | Very common |
| Skin and subcutaneous tissue disorders | Pruritus | Common |
| General disorders and administration site conditions | Injection site reactions | Very commonb |
| Fatigue | Common |
a The most commonly reported infections were Urinary tract infection (Common) and Upper respiratory tract infection (Common)
b Not reported in Effisayil 1
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. Serious infection (urinary tract infection) was reported in 1 patient (2.9%) in the spesolimab group and no patients 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 include injection site erythema, injection site swelling, injection site pain, injection site induration, and injection site warmth. Injection site reactions were typically mild-tomoderate in severity.
In patients with GPP treated with spesolimab in Effisayil 1, anti-drug antibodies (ADA) formed with a median onset of 2.3 weeks. Following intravenous administration of spesolimab 900 mg, 24% of patients had a maximum ADA titer greater than 4 000 and were Neutralising antibody-positive by end of the trial (weeks 12 to 17). Females appeared to have higher immunogenicity response; the percentage of patients with ADA titer greater than 4 000 was 30% in females, and 12% in males, respectively.
In some patients with ADA titer values >4 000, plasma spesolimab concentrations were reduced, with no apparent impact on pharmacokinetics at ADA titers below 4 000.
As the majority of patients did not experience a subsequent new flare in Effisayil 1, the data on re-treatment of patients with ADA (n=4) is limited. It is currently unknown if there is a correlation between the presence of ADA to spesolimab and maintenance of efficacy or hypersensitivity reactions upon re-treatment.
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.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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