Cibinqo Adverse Reactions

Summary of safety profile: The most commonly reported adverse reactions occurring in ≥2% of patients treated with CIBINQO in placebo-controlled studies were nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), vomiting (3.5%), dizziness (3.4%), blood creatine phosphokinase increased (3.1%), and abdominal pain upper (2.2%). The most frequent serious adverse reactions were infections (0.3%) (see Precautions).
Tabulated list of adverse reactions: A total of 3,802 patients were treated with CIBINQO in clinical studies in atopic dermatitis; among them 3,004 patients (representing 3,680 patient-years of exposure) were integrated for safety analysis, 1,549 patients with at least 48 weeks of exposure. The integrated safety analysis included 1,981 patients receiving a constant dose of abrocitinib 200 mg and 1,023 patients receiving a constant dose of 100 mg. Five placebo-controlled studies were integrated (703 patients on 100 mg once daily, 684 patients on 200 mg once daily and 438 patients on placebo) to evaluate the safety of CIBINQO in comparison to placebo for up to 16 weeks.
Listed in Table 5 are adverse reactions observed in atopic dermatitis clinical studies 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, adverse reactions are presented in order of decreasing seriousness. (See Table 5.)

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Description of selected adverse reactions: Infections: In placebo-controlled studies, for up to 16 weeks, infections have been reported in 27.4% of patients treated with placebo and in 34.9% and 34.8% of patients treated with CIBINQO 100 mg and 200 mg, respectively. Most infections were mild or moderate.
The percentage of patients reporting infection-related adverse drug reactions in the 200 mg and 100 mg groups compared to placebo were: herpes simplex (4.2% and 2.8% vs 1.4%), herpes zoster (1.2% and 0.6% vs 0%), pneumonia (0.1% and 0.1% vs 0%). Herpes simplex was more frequent in patients with a history of herpes simplex or eczema herpeticum. Most of the herpes zoster events involved a single dermatome and were non-serious.
Among all patients treated in clinical studies with consistent dosing regimens of either CIBINQO 100 mg or 200 mg, including the long-term extension study, the incidence rate of herpes zoster in patients treated with abrocitinib 200 mg (4.70 per 100 patient-years) was higher than that of patients treated with 100 mg (2.11 per 100 patient-years). Incidence rates of herpes zoster were also higher for patients 65 years of age and older (HR 3.83), patients with a medical history of herpes zoster (HR 3.53), patients with severe atopic dermatitis at baseline (HR 1.16), and a confirmed ALC <1.0 × 10³/mm³ prior to the event of herpes zoster (HR 2.04) (see Precautions).
In placebo-controlled studies, for up to 16 weeks, the rate of serious infections was 1.81 per 100 patient-years in patients treated with placebo, 3.32 per 100 patient-years in patients treated with CIBINQO 100 mg, and 1.12 per 100 patient-years in patients treated with CIBINQO 200 mg. Among all patients treated in clinical studies with consistent dosing regimens of either CIBINQO 100 mg or 200 mg, including the long-term extension study, the rate of serious infections was 2.20 per 100 patient-years in the CIBINQO 100 mg group and 2.69 per 100 patient-years in the CIBINQO 200 mg group. The most commonly reported serious infections were herpes simplex, herpes zoster, and pneumonia (see Precautions).
Opportunistic infections: Most opportunistic infections were non-serious cases of multidermatomal cutaneous herpes zoster. Among all patients treated in clinical studies with consistent dosing regimens of either CIBINQO 100 mg or 200 mg, including the long-term extension study, the rate of opportunistic infections was 0.58 per 100 patient-years in the CIBINQO 100 mg group and 1.17 per 100 patient-years in the CIBINQO 200 mg group. Most cases of opportunistic herpes zoster were mild or moderate.
Venous thromboembolism: Among all patients treated in clinical studies with consistent dosing regimen of either CIBINQO 100 mg or 200 mg, including the long-term extension study, the rate of PE was 0.13 per 100 patient-years in the CIBINQO 200 mg group and 0.06 per 100 patient-years in the CIBINQO 100 mg group. The rate of DVT was 0.09 per 100 patient-years in the CIBINQO 200 mg group and 0.13 per 100 patient-years in the CIBINQO 100 mg group (see Precautions).
Thrombocytopenia: In placebo-controlled studies, for up to 16 weeks, treatment with CIBINQO was associated with a dose-related decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which the platelet count returned towards baseline despite continued therapy. Confirmed platelet counts of <50 × 10³/mm³ were reported in 0.1% of patients exposed to CIBINQO 200 mg, and 0 patients treated with CIBINQO 100 mg or placebo. Among all patients treated in clinical studies with consistent dosing regimens of either CIBINQO 100 mg or 200 mg, including the long-term extension study, the rate of confirmed platelet counts of <50 × 10³/mm³ was 0.22 per 100 patient-years for 200 mg and 0 per 100 patient-years for 100 mg, most occurring at Week 4. Patients 65 years of age and older had a higher rate of platelet counts <75 × 10³/mm³ (see Precautions). There were no adolescent patients who developed platelet counts <75 × 10³/mm³.
Lymphopenia: In placebo-controlled studies, for up to 16 weeks, confirmed ALC <0.5 × 10³/mm³ occurred in 0.3% of patients treated with CIBINQO 200 mg and 0% of patients treated with CIBINQO 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure. Among all patients treated in clinical studies with consistent dosing regimens of either CIBINQO 100 mg or 200 mg, including the long-term extension, the rate of confirmed ALC <0.5 × 10³/mm³ was 0.40 per 100 patient-years for 200 mg and 0 per 100 patient-years for 100 mg, the highest rate was observed in patients 65 years of age and older (see Precautions). There were no adolescent patients who developed an ALC <0.5 × 10³/mm³.
Lipid elevations: In placebo-controlled studies, for up to 16 weeks, there was a dose-related percent increase in low-density lipoprotein cholesterol (LDL-c), total cholesterol, and high-density lipoprotein cholesterol (HDL-c) relative to placebo at Week 4 which remained elevated through the final visit in the treatment period. The median % change in LDL-c at Week 4 was 9.1%, 4.9% and -2.8% in patients exposed to 200 mg, 100 mg and placebo, respectively. The median % change in HDL-c at Week 4 was 20.0%, 12.1%, and 0% in patients exposed to 200 mg, 100 mg and placebo, respectively. Events related to hyperlipidaemia occurred in 0.4% of patients exposed to CIBINQO 100 mg, 0.6% of patients exposed to 200 mg, and 0% of patients exposed to placebo (see Precautions).
Creatine phosphokinase elevations (CPK): In placebo-controlled studies, for up to 16 weeks, events of blood CPK increased (>5 × ULN) were reported in 3.8% of patients treated with 200 mg of CIBINQO, 1.8% of patients treated with 100 mg of CIBINQO and 1.8% of patients treated with placebo. Most elevations were transient, and none led to discontinuation.
Nausea: In placebo-controlled studies, for up to 16 weeks, nausea was reported in 1.8% of patients treated with placebo and in 6.3% and 15.1% of patients treated with 100 mg and 200 mg, respectively. Discontinuation due to nausea occurred in 0.4% of patients treated with CIBINQO. Among patients with nausea, 63.5% of patients had onset of nausea in the first week of CIBINQO therapy. The median duration of nausea was 15 days. Most of the cases were mild to moderate in severity.
Psychiatric disorders: Patients who showed suicidal ideation(s)/behaviour(s) in relevant preliminary investigations were excluded from the clinical trials.
Adolescent population: A total of 635 adolescents (12 to less than 18 years of age) were treated with abrocitinib in clinical studies in atopic dermatitis representing 851.5 patient-years of exposure. The safety profile observed in adolescents in atopic dermatitis clinical studies was similar to that of the adult population (see Dosage & Administration).
Reporting of suspected adverse reactions: 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.