There are no available data from the use of teplizumab in pregnant women. Studies in animals have shown reproductive toxicity. Teplizumab is not recommended during pregnancy.
It is unknown whether teplizumab is excreted in human milk. Toxicological data in animals suggest excretion of teplizumab in milk of lactating mice. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with teplizumab and for 30 days after the last dose of treatment.
Women of childbearing potential have to use effective contraception during treatment with teplizumab and for 30 days after the last dose of treatment. Teplizumab is not recommended in women of childbearing potential not using contraception.
There are no clinical data available for teplizumab on the effects on fertility. Fertility and reproductive performance were unaffected in female and male mice treated with a surrogate anti-mouse CD3 antibody.
Teplizumab has a minor influence on the ability to drive and use machines. Fatigue has been reported.
The most frequently reported adverse reactions were lymphopenia (75%), leukopenia (58%), neutropenia (37%), and rash (36%). The most frequent serious adverse reaction was cytokine release syndrome (0.9%). Other serious adverse reactions included alanine aminotransferase increased (0.2%), aspartate aminotransferase increased (0.2%), lymphopenia (0.2%), neutropenia (0.2%), and infection (0.2%).
The adverse reactions occurring in patients in the pooled safety analysis of clinical studies and post-marketing setting are shown in the table below per MedDRA System Organ Class presented by frequency 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), not known: (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Adverse reactions:
| System organ class | Frequency | |||
| Very common | Common | Uncommon | Not known | |
| Infections and infestations | Infections1 | Epstein-Barr virus reactivation | ||
| Blood and lymphatic system disorders | Lymphopenia, Thrombocytopenia, Leukopenia, Neutropenia, Haemoglobin decreased | Eosinophilia | ||
| Immune system disorders | Cytokine release syndrome | Hypersensitivity1 | ||
| Nervous system disorders | Headache | |||
| Gastrointestinal disorders | Vomiting, Nausea | Diarrhoea, Abdominal pain | ||
| Hepatobiliary disorders | Alanine aminotransferase increased, Aspartate aminotransferase increased | Bilirubin increased | ||
| Skin and subcutaneous tissue disorders | Rash, Pruritus | Rash maculo- papular, Rash pruritic, Urticaria, Skin exfoliation | ||
| General disorders and administration site conditions | Pyrexia, Fatigue | Chills | Pain, Illness | |
1 Reported as serious – see "Description of selected adverse reactions".
In study TN-10, CRS was reported in 2% of patients treated with teplizumab.
In the pool of 7 clinical studies, 6% of patients treated with teplizumab developed CRS. In 14% of these patients, CRS was reported as serious. Liver transaminase elevations were observed more frequently in patients treated with teplizumab who experienced CRS.
In study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% of patients treated with teplizumab.
In the pool of 7 clinical studies, serious infections were reported in 3.1% of patients treated with teplizumab, including gastroenteritis, cellulitis, pneumonia, abscess, sepsis, and infectious mononucleosis.
In study TN-10, lymphopenia was reported in 73% of patients treated with teplizumab. The average lymphocyte count nadir occurred at day 5 of treatment, with recovery and return to baseline by week 6.
In the pool of 7 clinical studies, severe lymphopenia (<0.5 x 109 cells/L) lasting 1 week or longer occurred in 2% of patients treated with teplizumab and 0.5% of patients permanently discontinued treatment because of lymphopenia.
Hypersensitivity reactions were reported with teplizumab in study TN-10. Serum sickness was observed in 2% of patients treated with teplizumab.
In the pool of 7 clinical studies of patients:
In the pool of 7 clinical studies, haemoglobin decreased was reported in 23% of patients treated with teplizumab and thrombocytopenia was reported in 17% of patients treated with teplizumab; recovery occurred within 2 to 4 weeks of treatment. In clinical studies, 1.2% of patients treated with teplizumab discontinued treatment due to haemoglobin less than 85 g/L (or a decrease of more than 20 g/L to a value less than 100 g/L), and 1% discontinued teplizumab due to platelet count less than 50 x 109 platelets/L.
Liver enzyme and bilirubin elevations were observed in patients treated with teplizumab, both in the context of CRS and in patients without CRS. On laboratory analysis, 7.8% of patients treated with teplizumab experienced a peak ALT more than 3 times the ULN. For AST, 5.3% of patients treated with teplizumab experienced a peak AST more than 3 times the ULN. Most liver enzyme elevations were transient and resolved 1-2 weeks after treatment.
The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies.
In the placebo-controlled study in patients aged 8 years of age and older with stage 2 T1D (study TN-10), approximately 57% of patients treated with teplizumab developed treatment emergent anti-teplizumab antibodies, 46% of whom developed neutralising antibodies.
Based on the available data, no definitive conclusion can be made to characterise the effects of ADA on pharmacokinetics, pharmacodynamics, or effectiveness of teplizumab.
Immunogenicity data in children younger than 8 years of age have not been established.
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