Olumiant

SIDE EFFECTS

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

The following data include six randomized double-blind placebo-controlled studies (three Phase 2, three Phase 3) and a long-term extension study. All patients had moderately to severely active RA. Patients were randomized to placebo (1070 patients), OLUMIANT 2 mg (479 patients), or baricitinib 4 mg (997 patients).

Patients could be switched to baricitinib 4 mg from placebo or OLUMIANT 2 mg from as early as Week 12 depending on the study design. All patients initially randomized to placebo were switched to baricitinib 4 mg by Week 24.

During the 16-week treatment period, adverse events leading to discontinuation of treatment were reported by 35 patients (11.4 events per 100 patient-years) treated with placebo, 17 patients (12.1 events per 100 patient-years) with OLUMIANT 2 mg, and 40 patients (13.4 events per 100 patient-years) treated with baricitinib 4 mg.

During 0 to 52-week exposure, adverse events leading to discontinuation of treatment were reported by 31 patients (9.2 events per 100 patient-years) with OLUMIANT 2 mg, and 92 patients (10.2 events per 100 patient-years) treated with baricitinib 4 mg.

Overall Infections

During the 16-week treatment period, infections were reported by 253 patients (82.1 events per 100 patient-years) treated with placebo, 139 patients (99.1 events per 100 patient-years) treated with OLUMIANT 2 mg, and 298 patients (100.1 events per 100 patient-years) treated with baricitinib 4 mg.

During 0 to 52 week exposure, infections were reported by 200 patients (59.6 events per 100 patients-years) treated with OLUMIANT 2 mg, and 500 patients (55.3 events per 100 patient-years) treated with baricitinib 4 mg.

In the 0 to 52 week exposure population, the most commonly reported infections with OLUMIANT were viral upper respiratory tract infection, upper respiratory tract infection, urinary tract infection, and bronchitis.

Serious Infections

During the 16-week treatment period, serious infections were reported in 13 patients (4.2 events per 100 patient-years) treated with placebo, 5 patients (3.6 events per 100 patient-years) treated with OLUMIANT 2 mg, and 11 patients (3.7 events per 100 patient-years) treated with baricitinib 4 mg.

During 0 to 52 week exposure, serious infections were reported in 14 patients (4.2 events per 100 patient-years) treated with OLUMIANT 2 mg and 32 patients (3.5 events per 100 patient-years) treated with baricitinib 4 mg.

In the 0 to 52 week exposure population, the most commonly reported serious infections with OLUMIANT were pneumonia, herpes zoster, and urinary tract infection [see WARNINGS AND PRECAUTIONS].

Tuberculosis

During the 16-week treatment period, no events of tuberculosis were reported.

During 0 to 52 week exposure, events of tuberculosis were reported in 0 patients treated with OLUMIANT 2 mg and 1 patient (0.1 per 100 patient-years) treated with baricitinib 4 mg [see WARNINGS AND PRECAUTIONS].

Cases of disseminated tuberculosis were also reported.

Opportunistic Infections (excluding tuberculosis)

During the 16-week treatment period, opportunistic infections were reported in 2 patients (0.6 per 100 patient-years) treated with placebo, 0 patients treated with OLUMIANT 2 mg and 2 patients (0.7 per 100 patient-years) treated with baricitinib 4 mg.

During 0 to 52 week exposure, opportunistic infections were reported in 1 patient (0.3 per 100 patient-years) treated with OLUMIANT 2 mg and 5 patients (0.6 per 100 patient-years) treated with baricitinib 4 mg [see WARNINGS AND PRECAUTIONS].

Malignancy

During the 16-week treatment period, malignancies excluding non-melanoma skin cancers (NMSC) were reported in 0 patients treated with placebo, 1 patient (0.7 per 100 patient-years) treated with OLUMIANT 2 mg, and 1 patient (0.3 per 100 patient-years) treated with baricitinib 4 mg.

During the 0 to 52 week treatment period, malignancies excluding NMSC were reported in 2 patients (0.6 per 100 patient-years) treated with OLUMIANT 2 mg and 6 patients (0.7 per 100 patient-years) treated with baricitinib 4 mg [see WARNINGS AND PRECAUTIONS].

Venous Thrombosis

During the 16-week treatment period, venous thromboses (deep vein thrombosis or pulmonary embolism) were reported in 0 patients treated with placebo, 0 patients treated with OLUMIANT 2 mg, and 5 patients (1.7 per 100 patient-years) treated with baricitinib 4 mg.

During the 0 to 52 week treatment period, venous thromboses were reported in 2 patients (0.6 per 100 patient-years) treated with OLUMIANT 2 mg and 7 patients (0.8 per 100 patient-years) treated with baricitinib 4 mg.

Arterial Thrombosis

During the 16-week treatment period, arterial thromboses were reported in 1 patient treated with placebo (0.3 per 100 patient-years), 2 patients (1.4 per 100 patient-years) treated with OLUMIANT 2 mg, and 2 patients (0.7 per 100 patient-years) treated with baricitinib 4 mg.

During the 0 to 52 week treatment period, arterial thromboses were reported in 3 patients (0.9 per 100 patient-years) treated with OLUMIANT 2 mg and 3 patients (0.3 per 100 patient-years) treated with baricitinib 4 mg.

Laboratory Abnormalities

Neutropenia

During the 16-week treatment period, neutrophil counts below 1000 cells/mm³ occurred in 0% of patients treated with placebo, 0.6% of patients treated with OLUMIANT 2 mg, and 0.3% of patients treated with baricitinib 4 mg. There were no neutrophil counts below 500 cells/mm³ observed in any treatment group [see WARNINGS AND PRECAUTIONS].

Platelet Elevations

During the 16-week treatment period, increases in platelet counts above 600,000 cells/mm³ occurred in 1.1% of patients treated with placebo, 1.1% of patients treated with OLUMIANT 2 mg, and 2.0% of patients treated with baricitinib 4 mg. Mean platelet count increased by 3000 cells/mm³ at 16 weeks in patients treated with placebo, by 15,000 cells/mm³ at 16 weeks in patients treated with OLUMIANT 2 mg and by 23,000 cells/mm³ in patients treated with baricitinib 4 mg.

Liver Enzyme Elevations

Events of increases in liver enzymes ≥3 times the ULN were observed in patients treated with OLUMIANT [see WARNINGS AND PRECAUTIONS].

• During the 16-week treatment period, ALT elevations ≥3 times the ULN occurred in 1.0% of patients treated with placebo, 1.7% of patients treated with OLUMIANT 2 mg, and 1.4% of patients treated with baricitinib 4 mg.
• During the 16-week treatment period, AST elevations ≥ 3 times the ULN occurred in 0.8% of patients treated with placebo, 1.3% of patients treated with OLUMIANT 2 mg, and 0.8% of patients treated with baricitinib 4 mg.
• In a phase 3 study of DMARD naive patients, during the 24-week treatment period, ALT and AST elevations ≥3 times the ULN occurred in 1.9% and 0% of patients treated with methotrexate monotherapy, 1.9% and 1.3% of patients treated with baricitinib 4 mg monotherapy, and 4.7% and 1.9% of patients treated with baricitinib 4 mg plus methotrexate.

Lipid Elevations

In controlled clinical trials, OLUMIANT treatment was associated with dose-related increases in lipid parameters including total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol. Elevations were observed at 12 weeks and remained stable thereafter. During the 12-week treatment period, changes in lipid parameters are summarized below:

• Mean LDL cholesterol increased by 8 mg/dL in patients treated with OLUMIANT 2 mg and by 14 mg/dL in patients treated with baricitinib 4 mg.
• Mean HDL cholesterol increased by 7 mg/dL in patients treated with OLUMIANT 2 mg and by 9 mg/dL in patients treated with baricitinib 4 mg.
• The mean LDL/HDL ratio remained stable.
• Mean triglycerides increased by 7 mg/dL in patients treated with OLUMIANT 2 mg and by 15 mg/dL in patients treated with baricitinib 4 mg. [See WARNINGS AND PRECAUTIONS].

Creatine Phosphokinase (CPK)

OLUMIANT treatment was associated with increases in CPK within one week of starting OLUMIANT and plateauing after 8 to 12 weeks. At 16 weeks, the mean change in CPK for OLUMIANT 2 mg and baricitinib 4 mg was 37 IU/L and 52 IU/L, respectively.

Creatinine

In controlled clinical trials, dose-related increases in serum creatinine were observed with OLUMIANT treatment. At 52 weeks, the mean increase in serum creatinine was less than 0.1 mg/dL with baricitinib 4 mg. The clinical significance of the observed serum creatinine increases is unknown.

Other Adverse Reactions

Other adverse reactions are summarized in Table 4.

Table 4: Adverse Reactions occurring in greater than or equal to 1% of OLUMIANT 2 mg and Baricitinib 4 mg Treated Patients in Placebo-Controlled Trials

Additional adverse drug reactions occurring in fewer than 1% of patients: acne.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of OLUMIANT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Drug hypersensitivity (events such as rash, urticaria, and angioedema have been observed) [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Olumiant (Baricitinib Tablets)