Dupilumab interacts in the following cases:
Live and live attenuated vaccines should not be given concurrently with dupilumab as clinical safety and efficacy has not been established. Immune responses to TdaP vaccine and meningococcal polysaccharide vaccine were assessed. It is recommended that patients should be brought up to date with live and live attenuated immunisations in agreement with current immunisation guidelines prior to treatment with dupilumab.
Patients with known helminth infections were excluded from participation in clinical studies. Dupilumab may influence the immune response against helminth infections by inhibiting IL-4/IL-13 signaling. Patients with pre-existing helminth infections should be treated before initiating dupilumab. If patients become infected while receiving treatment with dupilumab and do not respond to anti-helminth treatment, treatment with dupilumab should be discontinued until infection resolves.
Cases of eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA) have been reported with dupilumab in adult patients who participated in the asthma development program. Cases of vasculitis consistent with EGPA have been reported with dupilumab and placebo in adult patients with co-morbid asthma in the CRSwNP development program. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis, conditions which are often treated with systemic corticosteroid therapy. These events usually, but not always, may be associated with the reduction of oral corticosteroid therapy.
There are limited amount of data from the use of dupilumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
It is unknown whether dupilumab is excreted in human milk or absorbed systemically after ingestion. A decision must be made whether to discontinue breast-feeding or to discontinue dupilumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Animal studies showed no impairment of fertility.
Dupilumab has no or negligible influence on the ability to drive or operate machinery.
h2 ®. Atopic dermatitis
The most common adverse reactions were injection site reactions, conjunctivitis, blepharitis, and oral herpes. Very rare cases of serum sickness/serum sickness-like reactions have been reported in the atopic dermatitis development program.
In the monotherapy studies, the proportion of patients who discontinued treatment due to adverse events was 1.9% of the placebo group, 1.9% of the dupilumab 300 mg Q2W group, 1.5% of the dupilumab 300 mg QW group . In the concomitant TCS study, the proportion of patients who discontinued treatment due to adverse events was 7.6% of the placebo + TCS group, 1.8% of the dupilumab 300 mg Q2W + TCS group, and 2.9% of the dupilumab 300 mg QW + TCS group.
The safety of dupilumab was evaluated in four randomized, double-blind, placebo-controlled studies and one dose-ranging study in patients with moderate-to-severe atopic dermatitis. In these 5 trials, 1,689 subjects were treated with subcutaneous injections of dupilumab, with or without concomitant topical corticosteroids (TCS). A total of 305 patients were treated with dupilumab for at least 1 year.
Listed below are adverse reactions observed in atopic dermatitis 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
List of adverse reactions in atopic dermatitis:
Common: Conjunctivitis, Oral herpes
Common: Eosinophilia
Very rare: Serum sickness/serum sickness-like reactions
Common: Headache
Common: Conjunctivitis allergic, Eye pruritus, Blepharitis
Very common: Injection site reactions
The safety of dupilumab was assessed in a study of 250 patients 12 to 17 years of age with moderate-to-severe atopic dermatitis (AD-1526). The safety profile of dupilumab in these patients followed through week 16 was similar to the safety profile from studies in adults with atopic dermatitis.
The long-term safety of dupilumab was assessed in an open-label extension study in patients 12 to 17 years of age with moderate-to-severe atopic dermatitis (AD-1434). The safety profile of dupilumab in patients followed through week 52 was similar to the safety profile observed at week 16 in AD-1526 study. The long-term safety profile of dupilumab observed in adolescents was consistent with that seen in adults with atopic dermatitis.
h2 ®. Asthma
The most common adverse reaction was injection site erythema. Anaphylactic reaction has been reported very rarely in the asthma development program .
In DRI12544 and QUEST studies, the proportion of patients who discontinued treatment due to adverse events was 4.3% of the placebo group, 3.2% of the dupilumab 200 mg Q2W group, and 6.1% of the dupilumab 300 mg Q2W group.
A total of 2,888 adult and adolescent patients with moderate-to-severe asthma were evaluated in 3 randomised, placebo-controlled, multicentre trials of 24 to 52 weeks duration (DRI12544, QUEST, and VENTURE). Of these, 2,678 had a history of 1 or more severe exacerbations in the year prior to enrolment despite regular use of medium-to-high dose inhaled corticosteroids plus an additional controller(s) (DRI12544 and QUEST). A total of 210 patients with oral corticosteroid-dependent asthma receiving high-dose inhaled corticosteroids plus up to two additional controllers were enrolled (VENTURE).
Listed below are adverse reactions observed in asthma 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
List of adverse reactions in asthma:
Very rare: Anaphylactic reaction
Very common: Injection site erythema
Common: Injection site oedema, Injection site pain, Injection site pruritus
h2 ®. Chronic rhinosinusitis with nasal polyposis (CRSwNP)
The most common adverse reactions were injection site reaction and injection site swelling.
In the safety pool, the proportion of patients who discontinued treatment due to adverse events was 2.0% of the dupilumab 300 mg Q2W group and 4.6% of the placebo group.
A total of 722 adult patients with CRSwNP were evaluated in 2 randomised, placebo-controlled, multicentre trials of 24 to 52 weeks duration (SINUS-24 and SINUS-52). The safety pool consisted of data from the first 24 weeks of treatment.
Listed below are adverse reactions observed in CRSwNP 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
List of adverse reactions in CRSwNP clinical studies:
Common: Conjunctivitis
Common: Eosinophilia
Common: Injection site reaction, Injection site swelling
Very rare cases of serum sickness/serum sickness-like reactions and anaphylactic reaction have been reported following administration of dupilumab.
Conjunctivitis occurred more frequently in atopic dermatitis patients who received dupilumab. Most patients with conjunctivitis recovered or were recovering during the treatment period. Among asthma patients frequency of conjunctivitis was low and similar between dupilumab and placebo. Among CRSwNP patients the frequency of conjunctivitis was higher in dupilumab than placebo, though lower than that observed in atopic dermatitis patients.
Eczema herpeticum was reported in <1% of the dupilumab groups and in <1% of the placebo group in the 16-week atopic dermatitis monotherapy studies. In the 52-week atopic dermatitis dupilumab + TCS study, eczema herpeticum was reported in 0.2% of the dupilumab + TCS group and 1.9% of the placebo + TCS group.
Dupilumab-treated patients had a greater mean initial increase from baseline in eosinophil count compared to patients treated with placebo. Eosinophil counts declined to near baseline levels during study treatment.
Treatment-emergent eosinophilia (≥ 5,000 cells/mcL) was reported in < 2% of dupilumab-treated patients and < 0.5% in placebo-treated patients.
In the 16-week atopic dermatitis monotherapy clinical studies, serious infections were reported in 1.0% of patients treated with placebo and 0.5% of patients treated with dupilumab. In the 52-week atopic dermatitis CHRONOS study, serious infections were reported in 0.6% of patients treated with placebo and 0.2% of patients treated with dupilumab.
No increase was observed in the overall incidence of infections with dupilumab compared to placebo in the safety pool for CRSwNP clinical studies. In the 52-week SINUS-52 study, serious infections were reported in 1.3% of patients treated with dupilumab and 1.3% of patients treated with placebo.
As with all therapeutic proteins, there is a potential for immunogenicity with dupilumab. Anti-Drug-Antibodies (ADA) responses were not generally associated with impact on dupilumab exposure, safety, or efficacy.
Approximately 5% of patients with atopic dermatitis, asthma, or CRSwNP who received dupilumab 300 mg Q2W for 52 weeks developed ADA to dupilumab; approximately 2% exhibited persistent ADA responses and approximately 2% had neutralizing antibodies.
Approximately 9% of patients with asthma who received dupilumab 200 mg Q2W for 52 weeks developed antibodies to dupilumab; approximately 4% exhibited persistent ADA responses and approximately 4% had neutralizing antibodies.
Across the 300 mg and 200 mg Q2W dosing regimens, approximately 4% of patients with atopic dermatitis, asthma, or CRSwNP in the placebo groups in the 52 week studies were also positive for antibodies to dupilumab; approximately 2% exhibited persistent ADA response and approximately 1% had neutralizing antibodies.
Less than 0.6% of patients exhibited high titer ADA responses associated with reduced exposure and efficacy. In addition, there was one patient with serum sickness and one with serum sickness-like reaction (<0.1%) associated with high ADA titers.
The safety profile observed in adolescents aged 12 to 17 years in atopic dermatitis clinical trials was similar to that seen in adults.
A total of 107 adolescents aged 12 to 17 years with asthma were enrolled in the 52 week QUEST study. The safety profile observed was similar to that seen in adults.
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