OLUMIANT SIDE EFFECTS

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Serious Infections
• Mortality
• Malignancy and Lymphoproliferative Disorders
• Major Adverse Cardiovascular Events
• Thrombosis
• Gastrointestinal Perforations
• Laboratory Abnormalities
• Hypersensitivity

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.

Adverse Reactions In Patients With Rheumatoid Arthritis

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 per 100 patient-years) treated with placebo, 17 patients (12.1 per 100 patient-years) with OLUMIANT 2 mg, and 40 patients (13.4 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 per 100 patient-years) with OLUMIANT 2 mg, and 92 patients (10.2 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 per 100 patientyears) treated with placebo, 139 patients (99.1 per 100 patient-years) treated with OLUMIANT 2 mg, and 298 patients (100.1 per 100 patient-years) treated with baricitinib 4 mg.

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

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.

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 patientyears) treated with baricitinib 4 mg.

Malignancies

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 patientyears) treated with OLUMIANT 2 mg and 6 patients (0.7 per 100 patient-years) treated with baricitinib 4 mg.

Thrombosis

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 thrombosis were reported in 3 patients (0.9 per 100 patient-years) treated with OLUMIANT 2 mg and 3 patients (0.3 per 100 patientyears) 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.

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.

• 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.

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 1.

Table 1: Adverse Reactions Occurring in Greater Than or Equal to 1% of OLUMIANT 2 mg and Baricitinib 4 mg Treated Patients in Placebo-Controlled Trials for Rheumatoid Arthritis

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

Adverse Reactions In Patients With COVID-19

The safety of OLUMIANT was evaluated in two randomized, double-blind, placebo-controlled clinical trials of hospitalized adults with COVID-19 for up to 29 days, in which 1307 patients received at least one dose of OLUMIANT 4 mg once daily, and 1310 patients received placebo, for up to 14 days or until hospital discharge, whichever occurred first. In these studies, prophylaxis for venous thromboembolic event (VTEs) was recommended or required for all patients unless a major contraindication was noted.

Overall, the safety profile observed in patients with COVID-19 treated with OLUMIANT was consistent with the safety profile in patients with rheumatoid arthritis.

Overall Infections

During the first 29 days of the randomized clinical trials, infections were reported in 194 patients (14.8%) treated with OLUMIANT 4 mg and by 219 patients (16.7%) treated with placebo. The most commonly reported infection with OLUMIANT was pneumonia (3.1%).

Serious Infections

During the first 29 days of the randomized clinical trials, serious infections were reported in 98 patients (7.5%) treated with OLUMIANT 4 mg and 120 patients (9.2%) treated with placebo. The most commonly reported serious infections with OLUMIANT were COVID-19 pneumonia (2.1%) and septic shock (2.1%).

Opportunistic Infections

During the first 29 days of the randomized clinical trials, opportunistic infections were reported in 12 patients (0.9%) treated with OLUMIANT 4 mg and 14 patients (1.1%) treated with placebo. Tuberculosis was reported in 1 patient (0.1%) treated with OLUMIANT 4 mg and 0 patients treated with placebo.

Venous Thrombosis Events

During the first 29 days of the randomized clinical trials, pulmonary embolism was reported in 20 patients (1.5%) treated with OLUMIANT 4 mg and 11 patients (0.8%) treated with placebo. Deep Vein Thrombosis was reported in 20 patients (1.5%) treated with OLUMIANT 4 mg and 18 patients (1.4%) treated with placebo.

Adverse drug reactions in greater than or equal to 1% of patients in trials for COVID-19 are summarized in Table 8.

Table 2 : Adverse Reactions That Occurred in Greater Than or Equal to 1% of Patients Treated with OLUMIANT 4 mg Treated Patients During the First 29 Days in Placebo-Controlled Trials for COVID-19

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)

SRC: NLM .