CIBINQO 8 Adverse Reactions

8.1 Adverse Reaction Overview

The most commonly reported dose-related adverse reactions (ARs) occurring in ≥2% of patients treated with CIBINQO in placebo-controlled studies were nausea (10.3%), headache (6.8%), herpes simplex (3.8%), acne (3.2%), blood creatine phosphokinase increased (2.6%), dizziness (2.3%), and vomiting (2.3%). The most frequent serious adverse reactions were infections.

8.2 Clinical Trial Adverse Reactions

Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.  Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 

A total of 2856 patients were treated with CIBINQO in Phase 2 and Phase 3 clinical studies in atopic dermatitis representing 1614 patient-years of exposure. There were 606 patients with more than 1 year of exposure to CIBINQO. The median age was 31.0 years, 12.7% were adolescents, and 5.1% were 65 years of age or older. Nearly half of the subjects (45.6%) were female. The majority of the subjects were White (72.2%); however, a substantial proportion were Asian (19.4%) and Black or African American (6%).

Four placebo‑controlled studies were integrated (608 patients on 100 mg once daily, 590 patients on 200 mg once daily and 342 patients on placebo) to evaluate the safety of CIBINQO in comparison to placebo for up to 16 weeks. Table 4 presents dose-related ADRs from these studies by Preferred term (PT) for CIBINQO listed by decreasing medical seriousness.

Other adverse reactions reported in less than 2% of patients treated with CIBINQO in placebo-controlled studies for up to 12 or 16 weeks included pneumonia, and herpes zoster. 

Overall Infections:

In placebo‑controlled studies, for up to 16 weeks, overall infections have been reported in 26.3% of patients treated with placebo and in 35.2% and 34.6% of patients treated with CIBINQO 100 mg and 200 mg, respectively. Most infections were mild or moderate. 

Serious Infections:

In placebo‑controlled studies, for up to 16 weeks, serious infections have been reported in 2 patients (2.31 per 100 patient‑years) treated with placebo, 6 patients (3.80 per 100 patient-years) treated with CIBINQO 100 mg, and 2 patients (1.28 per 100 patient-years) treated with CIBINQO 200 mg. Among all patients treated with CIBINQO, including the long-term extension study, serious infections were reported in 17 patients (2.65 per 100 patient-years) treated with CIBINQO 100 mg and 24 patients (2.33 per 100 patient-years) treated with CIBINQO 200 mg. The most commonly reported serious infections were herpes simplex, herpes zoster and pneumonia. 

Opportunistic Infections:

All observed opportunistic infections were cases of multidermatomal cutaneous herpes zoster. Among all patients treated with CIBINQO, including the long-term extension study, opportunistic infections were reported in 1 patient (0.16 per 100 patient-years) treated with CIBINQO 100 mg and 9 patients (0.87 per 100 patient-years) treated with CIBINQO 200 mg. Most cases of opportunistic herpes zoster were mild or moderate. 

Venous Thromboembolism:

Among all patients treated with CIBINQO, including the long-term extension study, PE was reported in 3 patients (0.18 per 100 patient-years), all treated with CIBINQO 200 mg. Events of DVT were reported in 2 patients (0.09 per 100 patient-years) treated with CIBINQO 200 mg 

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 1 patient (0.1%) exposed to CIBINQO 200 mg, 0 patients treated with CIBINQO 100 mg or placebo. Among all patients exposed to CIBINQO, including the long‑term extension study, confirmed platelet counts of <50 × 10³/mm³ were reported in 2 patients (0.1%), both treated with CIBINQO 200 mg. 

Lymphopenia:

In placebo‑controlled studies, for up to 16 weeks, confirmed ALC <0.5 × 10³/mm³ occurred in 2 patients (0.3%) treated with CIBINQO 200 mg and 0 patients treated with CIBINQO 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure. Among all patients exposed to CIBINQO, including the long-term extension study, confirmed ALC <0.5 × 10³/mm³ were reported in 4 patients (0.1%) treated with 200 mg of CIBINQO and 0 patients treated with CIBINQO 100 mg. 

Nausea:

Nausea was most frequent in the first week of CIBINQO therapy and generally resolved with continued therapy. The median duration of nausea was 15 days. Most of the cases were mild to moderate in severity. 

Pediatric population:

Of the 2,856 patients with atopic dermatitis exposed to CIBINQO, a total of 364 adolescents (12 to less than 18 years of age) were enrolled in CIBINQO studies. The safety profile observed in adolescents in atopic dermatitis clinical studies was similar to that of the adult population. There were no adolescent patients who developed platelet counts < 75 x 10³/mm³ or ALC < 0.5 x 10³/mm³. 

Elderly:

A total of 145 patients 65 years of age and older were enrolled in CIBINQO studies. The safety profile observed in elderly patients was similar to that of the adult population overall. A higher proportion of patients 65 years of age and older discontinued from clinical studies compared to younger patients. Among all patients exposed to CIBINQO, including the long‑term extension study, confirmed ALC <0.5 × 10³/mm³ occurred only in patients 65 years of age and older. A higher proportion of patients 65 years of age and older had platelet counts <75 × 10³/mm³. The incidence rate of herpes zoster in patients 65 years of age and older treated with CIBINQO (7.40 per 100 patient-years) was higher than that of patients 18 to less than 65 years of age (3.44 per 100 patient‑years) and less than 18 years of age (2.12 per 100 patient‑years). There are limited data in patients above 75 years of age.

8.2.1 Clinical Trial Adverse Reactions – Pediatrics

In the All Exposure Pool (which included subjects from 5 clinical studies plus a long-term extension study), adolescent subjects were more likely to have any Adverse Event (AE) relative to the 18 - <65-year-old subgroup. The results of an additional study conducted in adolescents using a combination therapy of CIBINQO with medicated topical treatments were consistent with this finding. There was no clustering of AEs driving the difference and, as such, the overall AE profile was similar.

In the All Exposure Pool, there were no meaningful differences in the proportions of adolescent subjects having serious infection relative to the other age groups. The IR for all herpes zoster infections was lowest in the adolescent subgroup relative to the other age groups. No adolescent subject had hematology laboratory values meeting pre-specified discontinuation criteria. In the Primary Pool, a similar proportion of adolescent subjects in the placebo and abrocitinib groups had shifts above 130 mg/dL in LDL.

8.3 Less Common Clinical Trial Adverse Reactions

Blood and lymphatic system disorders: Thrombocytopenia, Lymphopenia

Metabolism and nutrition disorders: Hyperlipidemia (dyslipidemia and hypercholesterolemia)

Vascular disorders: Venous thromboembolism (includes pulmonary embolism and deep vein thrombosis)

8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data

Clinical Trial Findings

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. There was no change in the LDL/HDL ratio or triglycerides. Events related to hyperlipidemia occurred in 1 patient (0.2%) exposed to CIBINQO 100 mg, 7 patients (1.2%) exposed to CIBINQO 200 mg and 0 patients exposed to placebo. 

Creatine Phosphokinase Elevations (CPK):

In placebo‑controlled studies, for up to 16 weeks, events of blood CPK increased were reported in 1.5% of patients treated with placebo, 2.3% and 2.9% of patients treated with 100 mg and 200 mg of CIBINQO, respectively. Most elevations were transient, and none led to discontinuation. In the clinical studies, there were no reported events of rhabdomyolysis.

8.5 Post-Market Adverse Reactions

Not applicable.