Guselkumab interacts in the following cases:
Guselkumab has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary.
There are no data from the use of guselkumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of guselkumab during pregnancy.
It is unknown whether guselkumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, and decrease to low concentrations soon afterwards; consequently, a risk to the breast-fed infant during this period cannot be excluded. A decision should be made whether to discontinue breast-feeding or to abstain from guselkumab therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Women of childbearing potential should use effective methods of contraception during treatment and for at least 12 weeks after treatment.
The effect of guselkumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Guselkumab has no or negligible influence on the ability to drive and use machines.
The most common adverse reaction was respiratory tract infections (approximately 8% of patients in ulcerative colitis studies, 11% of patients in the Crohn's disease studies, and 15% of patients in the psoriasis and psoriatic arthritis clinical studies).
The overall safety profile in patients treated with guselkumab is similar for patients with psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease.
Table 1 provides a list of adverse reactions from psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease clinical studies as well as adverse reactions reported from post-marketing experience. The adverse reactions are classified by MedDRA System Organ Class and frequency, 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 (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1. List of adverse reactions:
| System Organ Class | Frequency | Adverse reactions |
|---|---|---|
| Infections and infestations | Very common | Respiratory tract infections |
| Uncommon | Herpes simplex infections | |
| Uncommon | Tinea infections | |
| Uncommon | Gastroenteritis | |
| Immune system disorders | Rare | Hypersensitivity |
| Rare | Anaphylaxis | |
| Nervous system disorders | Common | Headache |
| Gastrointestinal disorders | Common | Diarrhoea |
| Skin and subcutaneous tissue disorders | Common | Rash |
| Uncommon | Urticaria | |
| Musculoskeletal and connective tissue disorders | Common | Arthralgia |
| General disorders and administration site conditions | Uncommon | Injection site reactions |
| Investigations | Common | Transaminases increased |
| Uncommon | Neutrophil count decreased |
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, liver function test abnormal, hypertransaminasaemia) were reported more frequently in the guselkumab-treated groups (8.6% in the 100 mg subcutaneous q4w group and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1 year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in the q4w group and 11.7% of patients in the q8w group.
Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤3 x upper limit of normal (ULN). Transaminase increases from >3 to ≤5 x ULN and >5 x ULN were low in frequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8w group (Table 2). A similar pattern of frequency by severity and by treatment group was observed through the end of the 2-year Phase III psoriatic arthritis clinical study.
Table 2. Frequency of patients with transaminase increases post-baseline in two Phase III psoriatic arthritis clinical studies:
| Through week 24a | Through 1 yearb | ||||
|---|---|---|---|---|---|
| Placebo N=370c | guselkumab 100 mg q8w N=373c | guselkumab 100 mg q4w N=371c | guselkumab 100 mg q8w N=373c | guselkumab 100 mg q4w N=371c | |
| ALT | |||||
| >1 to ≤3 x ULN | 30.0% | 28.2% | 35.0% | 33.5% | 41.2% |
| >3 to ≤5 x ULN | 1.4% | 1.1% | 2.7% | 1.6% | 4.6% |
| >5 x ULN | 0.8% | 0.8% | 1.1% | 1.1% | 1.1% |
| AST | |||||
| >1 to ≤3 x ULN | 20.0% | 18.8% | 21.6% | 22.8% | 27.8% |
| >3 to ≤5 x ULN | 0.5% | 1.6% | 1.6% | 2.9% | 3.8% |
| >5 x ULN | 1.1% | 0.5% | 1.6% | 0.5% | 1.6% |
a placebo-controlled period
b patients randomised to placebo at baseline and crossed over to guselkumab are not included
c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period
In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in the psoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did not increase by year of guselkumab treatment. Most transaminase increases were ≤3 x ULN.
In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In pooled Phase II and Phase III Crohn's disease clinical studies, through the placebo-controlled induction period (Week 0-12), adverse events of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased) were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebo group (0.6% of patients). In pooled Phase II and Phase III Crohn's disease clinical studies, through the reporting period of approximately one year, adverse events of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, hepatic function abnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 2.4% in the placebo group.
Based on laboratory assessments in pooled Phase II and Phase III Crohn's disease clinical studies, the frequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase III clinical studies. In pooled Phase II and Phase III Crohn's disease clinical studies, through the placebo-controlled period (Week 12), ALT (<1% of patients) and AST (<1% of patients) elevations ≥3x ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn's disease clinical studies, through the reporting period of approximately one year, ALT and/or AST elevations ≥3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse reaction of decreased neutrophil count was reported more frequently in the guselkumab-treated group (0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophil count was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in blood neutrophil count was mild, transient, not associated with infection and did not lead to discontinuation of treatment.
In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the guselkumab-treated group (1.1%) than in the placebo group (0.7%). Through Week 264, 5.8% of all guselkumab-treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumab through Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through the placebo-controlled period were similar to those observed in the psoriasis clinical studies.
In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 264, 0.4% of guselkumab injections were associated with injection site reactions. Injection site reactions were generally mild to moderate in severity; none were serious, and one led to discontinuation of guselkumab.
In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients that reported 1 or more injection site reactions was low and slightly higher in the guselkumab groups than in the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in the guselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinued guselkumab due to an injection site reaction during the placebo-controlled period of the psoriatic arthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection site reactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups respectively. Overall, the rate of injections associated with injection site reactions observed in psoriatic arthritis clinical studies through the placebo-controlled period was similar to rates observed in the psoriasis clinical studies.
In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections) in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two 100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection site reactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mild and none were serious.
In Phase II and Phase III Crohn's disease clinical studies through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in the treatment group which received guselkumab 200 mg intravenous induction followed by 200 mg subcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenous induction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild; none were serious.
In a Phase III Crohn's disease clinical study through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment group which received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3% (0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by 100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.
The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay. In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that were classified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumab developed antidrug antibodies in up to 264 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 5% had antibodies that were classified as neutralising, which equates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
In pooled Phase II and Phase III analyses in patients with ulcerative colitis, approximately 12% (n=58) of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified as neutralising, which equates to 2% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or the development of injection site reactions.
In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn's disease who were treated with intravenous induction followed by subcutaneous maintenance dose regimen, approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that were classified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients. In a Phase III analysis up to Week 48 in patients with Crohn's disease who were treated with subcutaneous induction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of these patients, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
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