Olumiant

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), and THROMBOSIS WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), and THROMBOSIS See full prescribing information for complete boxed warning. Increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with OLUMIANT if serious infection occurs until the infection is controlled. OLUMIANT should not be given to patients with active tuberculosis. Test for latent TB before and during therapy, except for COVID-19; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. ( 5.1 ) Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. ( 5.2 ) Malignancies have occurred in patients treated with OLUMIANT. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.3 ) Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.4 ) Thrombosis has occurred in patients treated with OLUMIANT. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. ( 5.5 ) SERIOUS INFECTIONS Patients treated with OLUMIANT are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Most patients with rheumatoid arthritis who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt OLUMIANT until the infection is controlled. Reported infections include: Active tuberculosis, which may present with pulmonary or extrapulmonary disease. OLUMIANT should not be given to patients with active tuberculosis. Patients, except those with COVID-19, should be tested for latent tuberculosis before initiating OLUMIANT and during therapy. If positive, start treatment for latent infection prior to OLUMIANT use. Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease. Bacterial, viral, and other infections due to opportunistic pathogens. The risks and benefits of treatment with OLUMIANT should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with OLUMIANT including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions ( 5.1 )]. MORTALITY In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor [see Warnings and Precautions ( 5.2 )]. MALIGNANCIES Lymphoma and other malignancies have been observed in patients treated with OLUMIANT. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions ( 5.3 )]. MAJOR ADVERSE CARDIOVASCULAR EVENTS In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OLUMIANT in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions ( 5.4 )]. THROMBOSIS Thrombosis, including deep venous thrombosis and pulmonary embolism, has been observed at an increased incidence in patients treated with OLUMIANT compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OLUMIANT in patients at risk. Patients with symptoms of thrombosis should discontinue OLUMIANT and be promptly evaluated. [see Warnings and Precautions ( 5.5 )].

5 WARNINGS AND PRECAUTIONS Hypersensitivity : Serious reactions have been reported. Discontinue OLUMIANT if a serious hypersensitivity reaction occurs. ( 5.6 ) Gastrointestinal Perforations : Monitor patients who may be at increased risk and evaluate promptly new onset of abdominal symptoms. ( 5.7 ) Hypoglycemia in Patients with Diabetes : Consider increased monitoring of blood glucose; advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia. ( 5.8 ) Laboratory Abnormalities : Monitor for changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids. ( 5.9 ) Vaccinations : Avoid use with live vaccines. ( 5.10 ) 5.1 Serious Infections Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients with rheumatoid arthritis receiving OLUMIANT. The most common serious infections reported with OLUMIANT included pneumonia, herpes zoster, and urinary tract infection [see Adverse Reactions ( 6.1 )] . Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with OLUMIANT. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid use of OLUMIANT in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating OLUMIANT in patients: with chronic or recurrent infection who have been exposed to tuberculosis with a history of a serious or an opportunistic infection who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. In patients with rheumatoid arthritis or alopecia areata, closely monitor for the development of signs and symptoms of infection during and after treatment with OLUMIANT. Interrupt OLUMIANT in patients with rheumatoid arthritis or alopecia areata, if the patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with OLUMIANT should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and OLUMIANT should be interrupted if the patient is not responding to therapy. Do not resume OLUMIANT until the infection is controlled. In patients with COVID-19, monitor for signs and symptoms of new infections during and after treatment with OLUMIANT. There is limited information regarding the use of OLUMIANT in patients with COVID-19 and concomitant active serious infections. The risks and benefits of treatment with OLUMIANT in COVID-19 patients with other concurrent infections should be considered. Tuberculosis Evaluate patients for active infection prior to administration of OLUMIANT. OLUMIANT should not be given to patients with active TB. Test patients with rheumatoid arthritis or alopecia areata for latent tuberculosis. Patients with rheumatoid arthritis or alopecia areata and latent tuberculosis (TB) should be treated with standard antimycobacterial therapy before initiating OLUMIANT. Consider anti-TB therapy prior to initiation of OLUMIANT in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. During OLUMIANT use, monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy. Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with OLUMIANT. If a patient develops herpes zoster, interrupt OLUMIANT treatment until the episode resolves. The impact of OLUMIANT on chronic viral hepatitis reactivation is unknown. Patients with evidence of active hepatitis B or C infection were excluded from clinical trials. In clinical trials in patients with rheumatoid arthritis or alopecia areata, patients who were positive for hepatitis C antibody but negative for hepatitis C virus RNA were permitted to enroll. Patients with positive hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were permitted to enroll; such patients should be monitored for expression of hepatitis B virus (HBV) DNA. Should HBV DNA be detected, consult with a hepatologist. Perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy with OLUMIANT. 5.2 Mortality In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT. 5.3 Malignancy and Lymphoproliferative Disorders Malignancies were observed in clinical studies of OLUMIANT [see Adverse Reactions ( 6.1 )] . In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers. Non-melanoma skin cancers Non-melanoma skin cancers (NMSCs) have been reported in patients treated with OLUMIANT. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. 5.4 Major Adverse Cardiovascular Events In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OLUMIANT, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OLUMIANT in patients that have experienced a myocardial infarction or stroke. 5.5 Thrombosis Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with OLUMIANT compared to placebo. In addition, arterial thrombosis events in the extremities have been reported in clinical studies with OLUMIANT. Many of these adverse events were serious and some resulted in death. There was no clear relationship between platelet count elevations and thrombotic events. In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. If clinical features of DVT/PE or arterial thrombosis occur, patients should discontinue OLUMIANT and be evaluated promptly and treated appropriately. Avoid OLUMIANT in patients that may be at increased risk of thrombosis. 5.6 Hypersensitivity Reactions such as angioedema, urticaria, and rash that may reflect drug hypersensitivity have been observed in patients receiving OLUMIANT, including serious reactions. If a serious hypersensitivity reaction occurs, promptly discontinue OLUMIANT while evaluating the potential causes of the reaction [see Adverse Reactions ( 6.2 )] . 5.7 Gastrointestinal Perforations Gastrointestinal perforations have been reported in clinical studies with OLUMIANT. Monitor OLUMIANT-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Evaluate promptly patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation. 5.8 Hypoglycemia in Patients with Diabetes Hypoglycemia, including severe hypoglycemia, has been reported following initiation of OLUMIANT and other JAK inhibitors in patients with diabetes. During treatment with OLUMIANT, consider increased monitoring of blood glucose as clinically indicated in patients with diabetes. Advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia. 5.9 Laboratory Abnormalities Neutropenia – Treatment with OLUMIANT was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm 3 ) compared to placebo. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ANC less than 1000 cells/mm 3 . In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ANC less than 1000 cells/mm 3 . Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ANC less than 500 cells/mm 3 . Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ANC [see Dosage and Administration ( 2.1 , 2.5 ) and Adverse Reactions ( 6.1 )] . Lymphopenia – ALC less than 500 cells/mm 3 were reported in OLUMIANT clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with OLUMIANT, but not placebo. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with an ALC less than 500 cells/mm 3 . In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with ALC less than 200 cells/mm 3 . Avoid initiation or interrupt OLUMIANT treatment in patients with COVID-19 and an ALC less than 200 cells/mm 3 . Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on ALC [see Dosage and Administration ( 2.1 , 2.5 )] . Anemia – Decreases in hemoglobin levels to less than 8 g/dL were reported in OLUMIANT clinical trials. In patients with rheumatoid arthritis or alopecia areata, avoid initiation or interrupt OLUMIANT treatment in patients with hemoglobin less than 8 g/dL. Evaluate at baseline and thereafter according to routine patient management. Adjust dosing based on hemoglobin levels [see Dosage and Administration ( 2.1 , 2.5 )] . In patients with COVID-19, there is limited information regarding use of OLUMIANT in patients with hemoglobin less than 8 g/dL. Liver Enzyme Elevations – Treatment with OLUMIANT was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥10 times the ULN were observed in patients in OLUMIANT clinical trials. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt OLUMIANT until this diagnosis is excluded [see Adverse Reactions ( 6.1 )] . Lipid Elevations – Treatment with OLUMIANT was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Assessment of lipid parameters should be performed approximately 12 weeks following OLUMIANT initiation in patients with rheumatoid arthritis or alopecia areata [see Adverse Reactions ( 6.1 )] . Manage patients according to clinical guidelines for the management of hyperlipidemia. 5.10 Vaccinations Avoid use of live vaccines with OLUMIANT. Update immunizations in patients with rheumatoid arthritis or alopecia areata prior to initiating OLUMIANT therapy in agreement with current immunization guidelines.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions ( 5.1 )] Mortality [see Warnings and Precautions ( 5.2 )] Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions ( 5.3 )] Major Adverse Cardiovascular Events [see Warnings and Precautions ( 5.4 )] Thrombosis [see Warnings and Precautions ( 5.5 )] Hypersensitivity [see Warnings and Precautions ( 5.6 )] Gastrointestinal Perforations [see Warnings and Precautions ( 5.7 )] Hypoglycemia in Patients with Diabetes [see Warnings and Precautions ( 5.8 )] Laboratory Abnormalities [see Warnings and Precautions ( 5.9 )] Adverse reactions reported in clinical trials (≥1%) are: Rheumatoid Arthritis : upper respiratory tract infections (URTIs), nausea, herpes simplex, and herpes zoster. ( 6.1 ) COVID-19: increases of liver enzymes, thrombocytosis, creatine phosphokinase increases, neutropenia, deep vein thrombosis, pulmonary embolism, and urinary tract infection (UTI) ( 6.1 ) Alopecia Areata : URTIs, headache, acne, hyperlipidemia, creatine phosphokinase increase, UTI, liver enzyme elevations, folliculitis, fatigue, lower respiratory tract infections, nausea, genital Candida infections, anemia, neutropenia, abdominal pain, herpes zoster, and weight increase ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 safety of OLUMIANT was evaluated in six randomized double-blind placebo-controlled studies (three Phase 2, three Phase 3) and a long-term extension study in patients with 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 patient-years) 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 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 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 [see Warnings and Precautions ( 5.1 )] . 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 ( 5.1 )] . 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 ( 5.1 )] . 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 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 ( 5.3 )] . 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 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/mm 3 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/mm 3 observed in any treatment group [see Warnings and Precautions ( 5.1 , 5.9 )] . Platelet Elevations – During the 16-week treatment period, increases in platelet counts above 600,000 cells/mm 3 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/mm 3 at 16 weeks in patients treated with placebo, by 15,000 cells/mm 3 at 16 weeks in patients treated with OLUMIANT 2 mg and by 23,000 cells/mm 3 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 ( 5.9 )] . 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 ( 5.9 )]. 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 8 . Table 8: 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 a Includes acute sinusitis, acute tonsillitis, chronic tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, sinusitis, tonsillitis, tracheitis, and upper respiratory tract infection. b Includes eczema herpeticum, genital herpes, herpes simplex, ophthalmic herpes simplex, and oral herpes. Events Weeks 0-16 Placebo OLUMIANT 2 mg Baricitinib 4 mg n=1070 (%) n=479 (%) n=997 (%) Upper respiratory tract infections a 11.7 16.3 14.7 Nausea 1.6 2.7 2.8 Herpes simplex b 0.7 0.8 1.8 Herpes zoster 0.4 1.0 1.4 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 9 . Table 9: Adverse Reactions That Occurred in Greater Than or Equal to 1% of Patients Treated with OLUMIANT 4 mg During the First 29 Days in Placebo-Controlled Trials for COVID-19 a As assessed by measured values within the clinical trial database. Frequencies are based on shifts from pre-treatment to post-treatment (with number at risk as the denominator), except for ALT and AST for which frequencies are based on observed elevation during treatment. b Creatine phosphokinase frequencies presented in the table were available for a single trial (COVID II) in patients with COVID-19 and do not represent integrated data. Placebo N = 1310 n (%) OLUMIANT 4 mg N = 1307 n (%) ALT ≥3 x ULN a 201(16.0) 230 (18.1) AST ≥3 x ULN a 117 (9.4) 149 (11.8) Thrombocytosis >600,000 cells/mm 3a 34 (4.6) 59 (7.9) Creatine phosphokinase (CPK) >5 x ULN a, b 38 (4.7) 36 (4.5) Neutropenia <1000 cells/mm 3a 22 (1.8) 26 (2.2) Deep vein thrombosis 18 (1.4) 20 (1.5) Pulmonary embolism 11 (0.8) 20 (1.5) Urinary tract infection 13 (1.0) 19 (1.5) Adverse Reactions in Patients with Alopecia Areata The safety of OLUMIANT was evaluated in two placebo-controlled trials in patients with severe alopecia areata. Patients were randomized to placebo (371 patients), OLUMIANT 2 mg (365 patients), or OLUMIANT 4 mg (540 patients). Of these, a total of 845 patients were treated with OLUMIANT for at least 1 year. Table 10 summarizes adverse reactions that occurred at a frequency of at least 1% in patients treated with OLUMIANT 2 mg once daily or OLUMIANT 4 mg once daily and more frequently than in patients treated with placebo during the 36-week placebo-controlled period of the alopecia areata clinical trials. Table 10: Adverse Reactions That Occurred in ≥1% of Patients Treated with OLUMIANT 2 mg or OLUMIANT 4 mg in Alopecia Areata Trials a %-study size adjusted percentages. b URTI includes: acute sinusitis, influenza, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, viral upper respiratory tract infection, viral sinusitis, viral pharyngitis, respiratory tract infection viral, rhinovirus infection and adenoiditis c Acne includes: acne and dermatitis acneiform. d Hyperlipidemia includes: hyperlipidaemia, hypercholesterolaemia, hypertriglyceridaemia, dyslipidaemia, lipids increased, low density lipoprotein increased, blood cholesterol increased, and blood triglycerides increased. e UTI includes: cystitis, urinary tract infection, white blood cells urine positive, urinary tract infection bacterial, and pyelonephritis. f Liver enzyme elevations includes: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, hepatic enzyme increased, gamma-glutamyl transferase increased, and hepatic function abnormal. g Folliculitis was most commonly localized in the scalp region associated with hair regrowth h LRTI includes: bronchitis, bronchiolitis, lower respiratory tract infection, pneumonia, COVID-19 pneumonia, and respiratory tract infection. i Genital Candida infections includes: vulvovaginal candidiasis, vulvovaginal mycotic infection, and genital infection fungal. j Neutropenia includes: neutropenia and neutrophil count decreased. k Abdominal pain includes: abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal discomfort. Adverse Reaction Weeks 0-36 Placebo OLUMIANT 2 mg OLUMIANT 4 mg N=371 (%) a N=365 (%) a N=540 (%) a Upper respiratory tract infections b (URTI) 19.9 18.4 21.3 Headache 5.4 5.5 6.6 Acne c 2.2 5.8 5.9 Hyperlipidemia d 3.0 3.6 5.9 Blood creatine phosphokinase increased 1.3 0.8 4.3 Urinary tract infections (UTI) e 2.2 3.8 3.7 Liver enzyme elevations f 2.4 1.1 3.0 Folliculitis g 0.8 1.4 2.2 Fatigue 1.1 0.8 2.2 Lower respiratory tract infections (LRTI) h 0.8 2.2 2.0 Nausea 1.6 2.7 2.0 Genital Candida infections i 0.3 2.2 1.3 Anemia 0.3 0.3 1.3 Neutropenia j 0.8 0.3 1.3 Abdominal pain k 2.2 3.8 0.9 Herpes zoster 0.5 1.4 0.9 Weight increased 0.3 1.6 0.9 In patients treated with any dose of baricitinib, adverse reactions that occurred in fewer than 1% of patients include arterial thrombosis, B cell lymphoma, lymphopenia, and fungal skin infections. Additional adverse reactions observed after Week 52: venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), and malignancy including non-melanoma skin cancer. Overall, the adverse reactions observed in patients with alopecia areata treated with OLUMIANT were consistent with the adverse reactions in patients with rheumatoid arthritis. 6.2 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 reported) [see Warnings and Precautions ( 5.6 )] . Metabolism and Nutrition Disorders : Hypoglycemia [see Warnings and Precautions ( 5.8 )] .

<table ID="t8" width="100%"><caption>Table 8: 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 </caption><col width="30.117%" align="left"/><col width="23.294%" align="left"/><col width="23.294%" align="left"/><col width="23.294%" align="left"/><tfoot><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^a Includes acute sinusitis, acute tonsillitis, chronic tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, sinusitis, tonsillitis, tracheitis, and upper respiratory tract infection. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^b Includes eczema herpeticum, genital herpes, herpes simplex, ophthalmic herpes simplex, and oral herpes. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="3" align="left" valign="bottom" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Events</content></td><td colspan="3" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Weeks 0-16</content></td></tr><tr><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">Placebo</content></td><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">OLUMIANT</content> <content styleCode="bold">2 mg</content></td><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">Baricitinib</content> <content styleCode="bold">4 mg</content></td></tr><tr><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">n=1070</content> <content styleCode="bold">(%)</content></td><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">n=479</content> <content styleCode="bold">(%)</content></td><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">n=997</content> <content styleCode="bold">(%)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Upper respiratory tract infections^a</td><td align="center" valign="middle" styleCode="Botrule Rrule">11.7 </td><td align="center" valign="middle" styleCode="Botrule Rrule">16.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">14.7 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Nausea </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.6 </td><td align="center" valign="middle" styleCode="Botrule Rrule">2.7 </td><td align="center" valign="middle" styleCode="Botrule Rrule">2.8 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Herpes simplex^b</td><td align="center" valign="middle" styleCode="Botrule Rrule">0.7 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.8 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Herpes zoster </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.4 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.0 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.4 </td></tr></tbody></table>

<table ID="t9" width="100%"><caption>Table 9: Adverse Reactions That Occurred in Greater Than or Equal to 1% of Patients Treated with OLUMIANT 4 mg During the First 29 Days in Placebo-Controlled Trials for COVID-19 </caption><col width="55.719%" align="left"/><col width="17.573%" align="left"/><col width="26.709%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^a As assessed by measured values within the clinical trial database. Frequencies are based on shifts from pre-treatment to post-treatment (with number at risk as the denominator), except for ALT and AST for which frequencies are based on observed elevation during treatment. </paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^b Creatine phosphokinase frequencies presented in the table were available for a single trial (COVID II) in patients with COVID-19 and do not represent integrated data. </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Placebo N = 1310</content> <content styleCode="bold">n (%)</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">OLUMIANT</content> <content styleCode="bold">4 mg N = 1307</content> <content styleCode="bold">n (%)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">ALT &#x2265;3 x ULN^a</td><td align="center" valign="top" styleCode="Botrule Rrule">201(16.0) </td><td align="center" valign="top" styleCode="Botrule Rrule">230 (18.1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">AST &#x2265;3 x ULN^a</td><td align="center" valign="top" styleCode="Botrule Rrule">117 (9.4) </td><td align="center" valign="top" styleCode="Botrule Rrule">149 (11.8) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Thrombocytosis &gt;600,000 cells/mm^3a</td><td align="center" valign="top" styleCode="Botrule Rrule">34 (4.6) </td><td align="center" valign="top" styleCode="Botrule Rrule">59 (7.9) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Creatine phosphokinase (CPK) &gt;5 x ULN^{a, b}</td><td align="center" valign="top" styleCode="Botrule Rrule">38 (4.7) </td><td align="center" valign="top" styleCode="Botrule Rrule">36 (4.5) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Neutropenia &lt;1000 cells/mm^3a</td><td align="center" valign="top" styleCode="Botrule Rrule">22 (1.8) </td><td align="center" valign="top" styleCode="Botrule Rrule">26 (2.2) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Deep vein thrombosis </td><td align="center" valign="top" styleCode="Botrule Rrule">18 (1.4) </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (1.5) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Pulmonary embolism </td><td align="center" valign="top" styleCode="Botrule Rrule">11 (0.8) </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (1.5) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Urinary tract infection </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1.0) </td><td align="center" valign="top" styleCode="Botrule Rrule">19 (1.5) </td></tr></tbody></table>

<table ID="t10" width="100%"><caption>Table 10: Adverse Reactions That Occurred in &#x2265;1% of Patients Treated with OLUMIANT 2 mg or OLUMIANT 4 mg in Alopecia Areata Trials </caption><col width="35.725%" align="left"/><col width="21.425%" align="left"/><col width="21.425%" align="left"/><col width="21.425%" align="left"/><tfoot><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^a %-study size adjusted percentages. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^b URTI includes: acute sinusitis, influenza, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, viral upper respiratory tract infection, viral sinusitis, viral pharyngitis, respiratory tract infection viral, rhinovirus infection and adenoiditis </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^c Acne includes: acne and dermatitis acneiform. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^d Hyperlipidemia includes: hyperlipidaemia, hypercholesterolaemia, hypertriglyceridaemia, dyslipidaemia, lipids increased, low density lipoprotein increased, blood cholesterol increased, and blood triglycerides increased. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^e UTI includes: cystitis, urinary tract infection, white blood cells urine positive, urinary tract infection bacterial, and pyelonephritis. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^f Liver enzyme elevations includes: transaminases increased, aspartate aminotransferase increased, alanine aminotransferase increased, hepatic enzyme increased, gamma-glutamyl transferase increased, and hepatic function abnormal. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^g Folliculitis was most commonly localized in the scalp region associated with hair regrowth </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^h LRTI includes: bronchitis, bronchiolitis, lower respiratory tract infection, pneumonia, COVID-19 pneumonia, and respiratory tract infection. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">ⁱ Genital Candida infections includes: vulvovaginal candidiasis, vulvovaginal mycotic infection, and genital infection fungal. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^j Neutropenia includes: neutropenia and neutrophil count decreased. </paragraph></td></tr><tr><td colspan="4" align="left" valign="top"><paragraph styleCode="footnote">^k Abdominal pain includes: abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal discomfort. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="3" align="left" valign="middle" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Adverse Reaction</content></td><td colspan="3" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Weeks 0-36</content></td></tr><tr><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">Placebo</content></td><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">OLUMIANT</content> <content styleCode="bold">2 mg</content></td><td align="center" valign="middle" styleCode="Rrule"><content styleCode="bold">OLUMIANT</content> <content styleCode="bold">4 mg</content></td></tr><tr><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">N=371</content> <content styleCode="bold">(%)</content><content styleCode="bold">^a</content></td><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">N=365</content> <content styleCode="bold">(%)</content><content styleCode="bold">^a</content></td><td align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">N=540</content> <content styleCode="bold">(%)</content><content styleCode="bold">^a</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Upper respiratory tract infections^b (URTI) </td><td align="center" valign="middle" styleCode="Botrule Rrule">19.9 </td><td align="center" valign="middle" styleCode="Botrule Rrule">18.4 </td><td align="center" valign="middle" styleCode="Botrule Rrule">21.3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Headache </td><td align="center" valign="middle" styleCode="Botrule Rrule">5.4 </td><td align="center" valign="middle" styleCode="Botrule Rrule">5.5 </td><td align="center" valign="middle" styleCode="Botrule Rrule">6.6 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Acne^c</td><td align="center" valign="middle" styleCode="Botrule Rrule">2.2 </td><td align="center" valign="middle" styleCode="Botrule Rrule">5.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">5.9 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hyperlipidemia^d</td><td align="center" valign="middle" styleCode="Botrule Rrule">3.0 </td><td align="center" valign="middle" styleCode="Botrule Rrule">3.6 </td><td align="center" valign="middle" styleCode="Botrule Rrule">5.9 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Blood creatine phosphokinase increased </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">4.3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Urinary tract infections (UTI)^e</td><td align="center" valign="middle" styleCode="Botrule Rrule">2.2 </td><td align="center" valign="middle" styleCode="Botrule Rrule">3.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">3.7 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Liver enzyme elevations^f</td><td align="center" valign="top" styleCode="Botrule Rrule">2.4 </td><td align="center" valign="top" styleCode="Botrule Rrule">1.1 </td><td align="center" valign="top" styleCode="Botrule Rrule">3.0 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Folliculitis^g</td><td align="center" valign="top" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="top" styleCode="Botrule Rrule">1.4 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.2 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Fatigue </td><td align="center" valign="top" styleCode="Botrule Rrule">1.1 </td><td align="center" valign="top" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.2 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Lower respiratory tract infections (LRTI)^h</td><td align="center" valign="top" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.2 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.0 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Nausea </td><td align="center" valign="top" styleCode="Botrule Rrule">1.6 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.7 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.0 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Genital Candida infectionsⁱ</td><td align="center" valign="top" styleCode="Botrule Rrule">0.3 </td><td align="center" valign="top" styleCode="Botrule Rrule">2.2 </td><td align="center" valign="top" styleCode="Botrule Rrule">1.3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Anemia </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Neutropenia^j</td><td align="center" valign="middle" styleCode="Botrule Rrule">0.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Abdominal pain^k</td><td align="center" valign="middle" styleCode="Botrule Rrule">2.2 </td><td align="center" valign="middle" styleCode="Botrule Rrule">3.8 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.9 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Herpes zoster </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.5 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.4 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.9 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Weight increased </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.3 </td><td align="center" valign="middle" styleCode="Botrule Rrule">1.6 </td><td align="center" valign="middle" styleCode="Botrule Rrule">0.9 </td></tr></tbody></table>