Study IV (BEACON) clinical trial design and select demographics1,2

Olumiant was evaluated in a randomized, double-blind, phase 3, placebo-controlled trial in 527 patients with moderately to severely active RA who had an inadequate response to one or more TNF inhibitors. The patients in this study could have had prior therapy with other biologic DMARDs.*

beacon trial icon

Key inclusion criteria

  • Inadequate response or intolerance to ≥1 TNF inhibitor. The patients in the study could have had prior therapy with other biologic DMARDs
  • Stable background cDMARDs

Primary endpoint

  • Proportion of patients who achieved ACR20 at week 12

Secondary measures included

  • ACR50 and ACR70
  • DAS28-CRP
  • HAQ-DI

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day.

*Biologic DMARDs included TNF inhibitors (etanercept, adalimumab, infliximab, golimumab, certolizumab), non-TNF inhibitors (abatacept, tocilizumab, rituximab, anakinra), and non-approved agents.

Baricitinib 4mg is not an approved dose.

RA=rheumatoid arthritis; TNF=tumor necrosis factor; DMARD=disease-modifying antirheumatic drug; cDMARD=conventional disease-modifying antirheumatic drug; bDMARD=biologic disease-modifying antirheumatic drug; ACR20/50/70=American College of Rheumatology 20%/50%/70% improvement criteria; DAS28=Disease Activity Score 28; CRP=C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index.

Patient characteristics and disease activity in the BEACON trial2,3

Beacon trials

hsCRP=high-sensitivity C-reactive protein; ESR=erythrocyte sedimentation rate; ACPA=anti-citrullinated peptide/protein antibody; RF=rheumatoid factor.

Data displayed are mean (standard deviation) unless otherwise stated. 959 patients were screened to randomize 527 patients in the following regions: US & Canada (44%), Europe (30%), Central & South America (10%), Asia (6%), and Rest of World (10%).

*Scores for the physician’s global assessment, the patient’s global assessment, and the patient’s assessment of pain range from 0 to 100 mm on a visual analog scale (VAS), with higher scores indicating greater levels of reported disease activity or pain.

Scores on the HAQ-DI range from 0 to 3, with higher scores indicating greater disability.

The upper limit of normal range (ULN) for the hsCRP level is 3 mg/L.

Olumiant reduced signs and symptoms of RA in TNFi-IR patients1,2,4

Patients receiving Olumiant + cDMARDs demonstrated higher ACR response rates vs placebo + cDMARDs at weeks 12 and 24

Chart showing patient responses to Olumiant + cDMARDS vs. placebo + cDMARDs

*p≤0.05; **p≤0.01; ***p≤0.001.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatments were considered non-responders in the analysis.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

TNFi-IR=tumor necrosis factor inhibitor-inadequate response; NRI=non-responder imputation.

See the BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION: WARNING RELATED TO SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS

SERIOUS INFECTIONS: Olumiant-treated patients are at risk for developing serious infections that may lead to hospitalization or death. Most patients 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 (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before and during Olumiant therapy. Consider 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.

Consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients for infection during and after Olumiant treatment. Monitor all patients for TB during treatment, even if the initial latent TB test was negative.

MALIGNANCIES: Lymphoma and other malignancies have been observed in Olumiant-treated patients.

THROMBOSIS: Thrombosis, including deep venous thrombosis and pulmonary embolism, was observed at an increased incidence in Olumiant-treated patients compared to placebo. There were also cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Promptly evaluate patients with symptoms of thrombosis.

Olumiant reduced the signs and symptoms of RA as early as week 11,4

Olumiant + cDMARDs demonstrated early symptom relief, with ACR20 responses seen as early as week 1

Chart showing ACR20 response rates time course

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatments were considered nonresponders.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

NRI=nonresponder imputation.

See the BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION: WARNING RELATED TO SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS

SERIOUS INFECTIONS: Olumiant-treated patients are at risk for developing serious infections that may lead to hospitalization or death. Most patients 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 (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before and during Olumiant therapy. Consider 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.

Consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients for infection during and after Olumiant treatment. Monitor all patients for TB during treatment, even if the initial latent TB test was negative.

MALIGNANCIES: Lymphoma and other malignancies have been observed in Olumiant-treated patients.

THROMBOSIS: Thrombosis, including deep venous thrombosis and pulmonary embolism, was observed at an increased incidence in Olumiant-treated patients compared to placebo. There were also cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Promptly evaluate patients with symptoms of thrombosis.

Efficacy results across individual ACR components1,2,4

Chart showing Efficacy results across individual ACR components

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Data were reported as mLOCF for all measures except HAQ-DI, which used mBOCF.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

LS=least squares; mLOCF=modified last observation carried forward; VAS=visual analog scale: 0=best, 100=worst; HAQ-DI=Health Assessment Questionnaire-Disability Index; 0=best, 3=worst; mBOCF=modified baseline observation carried forward;TJC=tender joint count; SJC=swollen joint count.

See the BEACON trial design

ACR20 response rate by prior treatment history at week 121,2,5

The data presented were from pre-specifieda or post hoc analysisb but were not type I error controlled. Therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Chart showing ACR20 response rate by prior treatment history at week 12

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatments were considered non-responders in the analysis.

Inclusion criteria for the BEACON study required inadequate response to ≥1 TNFi.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

NRI=non-responder imputation.

Prior treatment experience

  • 40% of the patients taking Olumiant 2 mg or placebo in the study had prior treatment experience with ≥2 TNFis
  • 27% of the patients taking Olumiant 2 mg or placebo in the study had prior treatment experience with ≥3 biologic DMARDs

See the BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION RELATED TO SERIOUS INFECTIONS

The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. 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 local disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant. Closely monitor patients for infections during and after Olumiant treatment. Interrupt Olumiant if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume Olumiant until the infection is controlled.

Patients receiving Olumiant showed significant improvement in physical function1,2

Differences in improvement between Olumiant + cDMARDs vs placebo + cDMARDs were significant at weeks 12 and 24

Chart showing differences in improvement between Olumian + cDMARDs vs placebo + cDMARDs

***p≤0.001.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Data were reported as modified baseline observation carried forward (mBOCF).

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

mBOCF=modified baseline observation carried forward.

See the BEACON trial design

Patients achieving minimal clinically important differences in physical function1,2,4

Percentage of patients achieving MCID in HAQ-DI at weeks 12 and 24

Chart showing patient’s HAQ-DI at week 12 and 24

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatments were considered non-responders in the analysis.

The data presented were from a pre-specified analysis but were not type I error controlled. Therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

MCID=minimal clinically important difference; NRI=non-responder imputation.

See the BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION RELATED TO TUBERCULOSIS

Evaluate and test patients for latent or active infection prior to initiating Olumiant. Treat patients with latent TB with standard antimycobacterial therapy before initiating Olumiant. Olumiant should not be given to patients with active TB. Monitor patients for development of signs and symptoms of TB.

In TNFi-IR patients, more patients treated with Olumiant achieved DAS28-CRP <2.6 vs placebo at week 121,2,4

Percentage of patients achieving DAS28 <2.6 and ≤3.2 at weeks 12 and 24

Chart showing patient’s DAS at weeks 12 and 24

*p≤0.05.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatments were considered non-responders in the analysis.

DAS28 ≤3.2 presented were from a pre-specified analysis but were not type I error controlled. Therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

NRI=non-responder imputation.

See the BEACON trial design

DAS28 change from baseline through week 241,2

Chart showing DAS28 change from baseline through week 24

***p≤0.001.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Data were reported as modified baseline observation carried forward (mBOCF).

The data presented at week 24 were from a pre-specified analysis but were not type I error controlled. Therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

mBOCF=modified baseline observation carried forward.

See the BEACON trial design

Reference: 1. Olumiant Prescribing Information, Indianapolis, IN Lilly USA, LLC. 2. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-1252. 3. Smolen JS, Kremer JM, Gaich CL, et al. Patient-reported outcomes from a randomised phase III study of baricitinib inpatients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON) [published online ahead of print October 31, 2016]. Ann Rheum Dis. 2016;0:1-7 4. Genovese MC, Kremer J, Zamani O, et al. Baricitinib inpatients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(suppl):1-30. 5. Genovese MC, Kremer JM, Kartman CE, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology. 2018;57:900-908.

INDICATION AND IMPORTANT SAFETY INFORMATION WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS
INDICATION

Olumiant is a Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.

Limitation of Use: Use of Olumiant in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.

IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) tablets

WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS

SERIOUS INFECTIONS: Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients 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 (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before initiating Olumiant and during therapy. Treatment for latent infection should be considered 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.

Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MALIGNANCIES: Lymphoma and other malignancies have been observed in patients treated with Olumiant.

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, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Patients with symptoms of thrombosis should be promptly evaluated.

WARNINGS AND PRECAUTIONS

SERIOUS INFECTIONS: The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. 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 local disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid 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 TB
  • 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.

Closely monitor patients for infections during and after Olumiant treatment. Interrupt Olumiant if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume Olumiant until the infection is controlled.

Tuberculosis – Before initiating Olumiant evaluate and test patients for latent or active infection and treat patients with latent TB with standard antimycobacterial therapy. Olumiant should not be given to patients with active TB. Consider anti-TB therapy prior to initiating 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. Monitor patients for TB during Olumiant treatment.

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. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.

MALIGNANCY AND LYMPHOPROLIFERATIVE DISORDERS: Malignancies were observed in Olumiant clinical studies. Consider the risks and benefits of Olumiant prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing Olumiant in patients who develop a malignancy. NMSCs were reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

THROMBOSIS: Thrombosis, including DVT and PE, has been observed at an increased incidence in Olumiant-treated patients 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. Use Olumiant with caution in patients who may be at increased risk of thrombosis. If clinical features of DVT/PE or arterial thrombosis occur, evaluate patients promptly and treat appropriately.

GASTROINTESTINAL PERFORATIONS: Gastrointestinal perforations have been reported in Olumiant clinical studies, although the role of JAK inhibition in these events is not known. Use Olumiant with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.

LABORATORY ABNORMALITIES: Neutropenia – Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3) compared to placebo. Avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.

Lymphopenia – Absolute lymphocyte count (ALC) <500 cells/mm3 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. Avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.

Anemia – Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.

Liver Enzyme Elevations – Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases to ≥5x and ≥10x upper limit of normal were observed for both ALT and AST in patients in Olumiant clinical trials.

Evaluate at baseline and thereafter according to routine patient management. Promptly investigate the cause of liver enzyme elevation 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.

Lipid Elevations – Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation. Manage patients according to clinical guidelines for the management of hyperlipidemia.

VACCINATIONS: Avoid use of live vaccines with Olumiant. Update immunizations in agreement with current immunization guidelines prior to initiating Olumiant therapy.

ADVERSE REACTIONS

Adverse reactions (≥1%) include: upper respiratory tract infections (16.3%, 14.7%, 11.7%), nausea (2.7%, 2.8%, 1.6%), herpes simplex (0.8%, 1.8%, 0.7%), and herpes zoster (1.0%, 1.4%, 0.4%) for Olumiant 2 mg, baricitinib 4 mg, and placebo, respectively.

USE IN SPECIFIC POPULATIONS

PREGNANCY AND LACTATION: No information is available to support the use of Olumiant in pregnancy or lactation. Advise women not to breastfeed during treatment with Olumiant.

HEPATIC AND RENAL IMPAIRMENT: Olumiant is not recommended in patients with severe hepatic impairment or in patients with moderate or severe renal impairment.

Please see full Prescribing Information, including Boxed Warning about Serious Infections, Malignancies, and Thrombosis, and Medication Guide.

BA HCP ISI 01JUN2018