A trial designed for patients still in need1-3

BEACON (Study IV) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm

Olumiant was evaluated in a 24-week randomized, double-blind, phase 3, placebo-controlled trial in 527 patients with moderately to severely active RA who had an inadequate response or intolerance to one or more TNF inhibitors; the patients could have had prior therapy with other biologic DMARDs.* The patients in this study were on stable background cDMARDs.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Baricitinib 4 mg is not an approved dose.

Primary endpoint

  • Proportion of patients who achieved ACR20 response at week 12

Select inclusion criteria

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

Secondary measures included

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

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

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

Patient characteristics and disease activity in the BEACON trial2,4,5

Data displayed are n (%) unless otherwise noted.

Baricitinib 4 mg is not an approved dose.

*Three patients (2 in Olumiant 2 mg, 1 in baricitinib 4 mg) received ≥3 concomitant cDMARDs.

959 patients were screened to randomize 527 patients in the following regions: US and Canada (44%), Europe (30%), Central and South America (10%), Asia (6%), and Rest of World (10%).

Data displayed are mean (standard deviation).

Baricitinib 4 mg is not an approved dose.

Scores for the physician global assessment, patient global assessment, and 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.

SD=standard deviation; ACPA=anti-citrullinated peptide/protein antibody; RF=rheumatoid factor; bDMARD=biologic disease-modifying antirheumatic drug; MTX=methotrexate; hsCRP=high-sensitivity C-reactive protein.

Reach for results

Olumiant reduced the signs and symptoms of RA1,2,5

TNFi-IR patients receiving Olumiant demonstrated higher ACR response rates vs placebo at weeks 12 and 24

Statistical significance declared without control for multiple comparisons in the hierarchical testing.

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. Baricitinib 4 mg is not an approved dose.

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

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.

Results TNFi-IR patients can feel

Pain improvement at weeks 1, 12, and 241,7

Percentage of TNFi-IR patients achieving ≥30%, ≥50%, and ≥70% reduction in pain from baseline

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Baricitinib 4 mg is not an approved dose.

Missing data for pain analyses, tender and swollen joint counts were reported as mLOCF.

The data presented were from a post hoc analysis of the ACR component pain (VAS, 0-100) and 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.

In BEACON (TNFi-IR) (Olumiant 2 mg/day n=174; placebo n=176), 49% of patients receiving Olumiant + cDMARDs achieved ACR20 response at week 12 vs 27% of patients receiving placebo + cDMARDs. Patients who discontinued treatments were considered non-responders in the analysis.

For number of tender joints (0-68), the mean for placebo + cDMARD patients was 28 at baseline and 20 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 31 at baseline and 19 at week 12.

For number of swollen joints (0-66), the mean for placebo + cDMARD patients was 17 at baseline and 12 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 19 at baseline and 10 at week 12.

For pain, the mean score (VAS, 0-100) for placebo + cDMARD patients was 65 at baseline and 55 at week 12 and for Olumiant 2 mg + cDMARD patients the mean score was 62 at baseline and 46 at week 12.

See the BEACON trial design

TNFi-IR=tumor necrosis factor inhibitor-inadequate response; mLoCF=modified last observation carried forward; cDMARD=conventional disease-modifying antirheumatic drug; ACR20=American College of Rheumatology 20% improvement criteria; VAS=visual analog scale;0=best, 100=worst.

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.

Improved physical function is within reach with Olumiant2

Differences in HAQ-DI improvement for TNFi-IR patients between Olumiant vs placebo were significant at week 24

Statistical significance declared without control for multiple comparisons in the hierarchical testing.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Baricitinib 4 mg is not an approved dose.

Missing data were reported as mLOCF except for week 12, which was reported as mBOCF.

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

Mean baseline HAQ-DI was 1.71 for Olumiant 2 mg and 1.78 for placebo.

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.

Help TNFi-IR patients achieve low disease activity1,5

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

Statistical significance declared without control for multiple comparisons in the hierarchical testing.

From week 16, non-responding patients could be rescued to receive baricitinib 4 mg/day. Patients who were rescued or discontinued treatment were considered non-responders in the analysis. Baricitinib 4 mg is not an approved dose.

DAS28 ≤3.2 presented were from a prespecified 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.

See the BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION RELATED TO 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 starting therapy with Olumiant.

ACR responses for Olumiant and placebo in cDMARD-IR patients1

Olumiant is not indicated for cDMARD-IR patients.

Patients who were rescued or discontinued treatments were considered non-responders in the analysis.

BUILD (Study III) was a 24-week trial in 684 patients with moderately to severely active RA who had an inadequate response or intolerance to cDMARDs. Patients received Olumiant 2 mg or baricitinib 4 mg once daily or placebo added to existing background cDMARD treatment. From week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. Baricitinib 4 mg is not an approved dose. Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

cDMARD-IR=conventional disease-modifying antirheumatic drug-inadequate response.

References: 1. Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018. 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. Genovese MC, Kremer J, Kartman C, et al. Previous biologic disease-modifying antirheumatic drug exposure and efficacy and safety analysis from a phase 3 study of baricitinib in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitors. Poster presented at: ACR Annual; 2015; San Francisco, CA. 4. Smolen JS, Kremer JM, Gaich CL, et al. Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Dis. 2017;0:1-7. 5. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(suppl):1-30. 6. Genovese MC, Kremer JM, Kartman CE, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018;57:900-908. 7. Taylor P, Zhu B, Gaich C, et al. SAT0055 Baricitinib showed rapid and greater reduction in pain compared to adalimumab or placebo in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76:788. 8. Pope JE, Quebe A, Zhu B, et al. Assessment of pain relief with baricitinib by treatment history in patients with refractory rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

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

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