Inebilizumab interacts in the following cases:
Inebilizumab has not been studied in patients with severe renal or hepatic impairment. However, dose adjustment based on renal or hepatic function is not warranted because immunoglobulin (Ig) G monoclonal antibodies are not primarily cleared via renal or hepatic pathways.
Inebilizumab has been tested, and is intended to be used, as monotherapy for this indication. No data are available on the safety or efficacy of combining inebilizumab with other immunosuppressants. In the pivotal study, a 2-week course of oral corticosteroids (plus a 1-week taper) was given to all subjects following the first administration of inebilizumab.
Concomitant usage of inebilizumab with immunosuppressants, including systemic corticosteroids, may increase the risk of infection. The effects of inebilizumab on B cells and immunoglobulins may persist for 6 months or longer following its administration.
When initiating inebilizumab after other immunosuppressive therapies with prolonged immune effects or initiating other immunosuppressive therapies with prolonged immune effects after inebilizumab, the duration and mode of action of these medicinal products should be taken into account because of potential additive immunosuppressive effects.
Patients with a known congenital or acquired immunodeficiency, including HIV infection or splenectomy, have not been studied.
Patients positive for HCV were excluded from clinical trials with inebilizumab. Baseline screening for HCV is required to detect and start treatment prior to initiating inebilizumab treatment.
Patients who are chronic carriers of HBV [HBsAg+] should consult a liver disease expert before starting and during treatment.
There are limited amount of data from the use of inebilizumab in pregnant women. Inebilizumab is a humanised IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier.
Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell-depleting antibodies during pregnancy.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity; however, they have shown a B-cell depletion in the foetal livers of progeny.
Treatment with inebilizumab should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.
In case of exposure during pregnancy, depletion of B cells may be expected in newborns due to the pharmacological properties of the product and findings from animal studies. The potential duration of B-cell depletion in infants exposed to inebilizumab in utero, and the impact of B-cell depletion on the safety and effectiveness of vaccines, are unknown. Consequently, newborns should be monitored for B-cell depletion and vaccinations with live virus vaccines, such as Bacillus Calmette-Guérin (BCG) vaccine, should be postponed until the infant’s B-cell count has recovered.
The use of inebilizumab in women during lactation has not been studied. It is unknown whether inebilizumab is excreted 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, a risk to the breast-fed child cannot be excluded during this short period. Afterwards, inebilizumab could be used during breast feeding if clinically needed. However, if the patient was treated with inebilizumab up to the last few months of pregnancy, breast feeding can be started immediately after birth.
Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving inebilizumab and for 6 months after the last administration of inebilizumab.
There are limited data on the effect of inebilizumab on human fertility; however, studies in animals have shown reduced fertility. The clinical significance of these nonclinical findings is not known.
The pharmacological activity and adverse reactions reported to date suggest that inebilizumab has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse reactions by inebilizumab-treated patients were urinary tract infection (26.2%), nasopharyngitis (20.9%), upper respiratory tract infection (15.6%), arthralgia (17.3%), and back pain (13.8%) across both the RCP and OLP. The most frequently reported serious adverse reactions by inebilizumab-treated patients across the RCP and OLP were infections (11.1%) (including urinary tract infections (4.0%), pneumonia (1.8%)) and NMOSD (1.8%).
Adverse reactions reported in the clinical trial of inebilizumab in NMOSD are listed in the table below according to the following 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).
Adverse reactions:
| MedDRA System Organ Class | Adverse reaction | Frequency |
|---|---|---|
| Infections and infestations | Urinary tract infection, respiratory tract infection, nasopharingitis, influenza | Very Common |
| Pneumonia, cellulitis, herpes zoster, sinusitis | Common | |
| Sepsis, subcutaneous abscess, bronchiolitis | Uncommon | |
| Blood and lymphatic system disorders | Lymphopenia, Neutropenia, Late-onset neutropenia | Common |
| Musculoskeletal and connective tissue disorders | Arthralgia, back pain | Very Common |
| Investigations | Immunoglobulins decreased | Very Common |
| Injury, poisoning and procedural complications | Infusion-related reaction | Very Common |
Inebilizumab can cause infusion-related reactions, which can include headache, nausea, somnolence, dyspnoea, fever, myalgia, rash, or other symptoms. All patients were given premedication. Infusion reactions were observed in 9.2% of NMOSD patients during the first course of inebilizumab compared to 10.7% of placebo-treated patients. Infusion-related reactions were most common with the first infusion but were observed during subsequent infusions. The majority of infusion-related reactions reported in inebilizumab-treated patients were either mild or moderate in severity.
An infection was reported by 74.7% of NMOSD patients treated with inebilizumab across the RCP and OLP. The most common infections included urinary tract infection (26.2%), nasopharyngitis (20.9%), and upper respiratory tract infection (15.6%), influenza (8.9%), and bronchitis (6.7%).
Serious infections reported by more than one inebilizumab-treated patient were urinary tract infection (4.0%) and pneumonia (1.8%).
During the RCP, no opportunistic infections occurred in either treatment group, and a single Grade 4 infectious adverse reaction (atypical pneumonia) occurred in a patient treated with inebilizumab. During the OLP, 2 inebilizumab-treated patients (0.9%) experienced an opportunistic infection (one of which was not confirmed) and 3 inebilizumab-treated patients (1.4%) experienced a Grade 4 infectious adverse reaction.
Consistent with its mechanism of action, average immunoglobulin levels decreased with inebilizumab use. At the end of the 6.5-month RCP, the proportion of patients with levels below the lower limit of normal was as follows: IgA 9.8% inebilizumab and 3.1% placebo, IgE 10.6% inebilizumab and 12.5% placebo, IgG 3.8% inebilizumab and 9.4% placebo, and IgM 29.3% inebilizumab and 15.6% placebo. A single adverse reaction of IgG decreased was reported (Grade 2, during the OLP). The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal at year 1 was 7.4% and at year 2 was 9.9%. With a median exposure of 3.2 years, the frequency of moderate IgG reduction (300 to <500 mg/dL) was 14.2% and the frequency of severe IgG reduction (<300 mg/dL) was 3.6%.
After 6.5 months of treatment, neutrophil counts between 1.0-1.5 x109/L (Grade 2) were observed in 7.5% of inebilizumab-treated patients versus 1.8% of placebo-treated patients. Neutrophil counts between 0.5-1.0 x109/L (Grade 3) were observed in 1.7% of inebilizumab-treated patients versus 0% of placebo-treated patients. Neutropenia was generally transient and was not associated with serious infections.
After 6.5 months of treatment, a reduction in lymphocyte counts was observed more commonly in patients treated with inebilizumab than placebo: lymphocyte counts between 500 - <800/mm³ (Grade 2) were observed in 21.4% of inebilizumab-treated patients versus 12.5% of placebo-treated patients. Lymphocyte counts between 200 - <500/mm³ (Grade 3) were observed in 2.9% of inebilizumab-treated patients versus 1.8% of placebo-treated patients. This finding is consistent with the mechanism of action of B-cell depletion since B cells are a subset of the lymphocyte population.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
