A trial designed for patients still in need2,3

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

Study IV (BEACON) clinical trial design for Olumiant (baricitinib).

Olumiant was evaluated in a 24-week, randomized, double-blind, placebo-controlled trial in 527 patients with moderately to severely active RA who had an inadequate response or intolerance to at least 1 TNF inhibitor. Patients received Olumiant 2 mg (n=174) or baricitinib 4 mg (n=177) once daily or placebo (n=176), added to stable background cDMARD treatment. From week 16, non-responding patients could be rescued to a higher dose (baricitinib 4 mg/day). Baricitinib 4 mg is not an approved dose. The primary endpoint was the proportion of patients achieving ACR20 response at week 12.

cDMARD=conventional disease-modifying antirheumatic drug; RA=rheumatoid arthritis; TNF=tumor necrosis factor; ACR20=American College of Rheumatology 20% improvement criteria.

Olumiant demonstrated significantly greater ACR20, ACR50, and ACR70 response rates vs placebo at weeks 12 and 242-4

ACR20/50/70 Response Rates

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

ACR20 is defined as achieving a 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 remaining ACR components.5

From week 16, non-responding patients could be rescued to a higher dose which is not approved. Patients who were rescued or discontinued treatment were considered non-responders in the analysis.

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

See the BEACON clinical trial design

ACR20/50/70=American College of Rheumatology 20%/50%/70% improvement criteria; ACR=American College of Rheumatology; cDMARD=conventional disease modifying antirheumatic drug; ACR20=American College of Rheumatology 20% improvement criteria.

Percentage of patients achieving ≥30%, 50%, and 70% reduction in pain from baseline2,6

Graph - BEACON pain improvement at weeks 1, 12, and 24

From week 16, non-responding patients could be rescued to a higher dose which is not approved.

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.

See the BEACON trial design

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.

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.

Olumiant demonstrated significant improvement in physical function vs placebo at week 242,3

Graph - BEACON HAQ-DI over time

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

HAQ-DI is a patient-reported questionnaire that measures the degree of difficulty experienced in completing activities of daily living such as dressing and grooming, arising, eating, walking, hygiene, reaching and gripping.7

From week 16, non-responding patients could be rescued to a higher dose which is not approved.

Missing data were reported as modified last observation carried forward (mLOCF) except for week 12, which was reported as modified baseline observation carried forward (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 + cDMARDs and 1.78 for placebo + cDMARDs.

See the BEACON clinical trial design

HAQ-DI=Health Assessment Questionnaire-Disability Index; LS=least squares; cDMARDs=conventional disease-modifying antirheumatic drugs.

Study IV (BEACON) clinical trial

Learn more about the Study IV (BEACON) clinical trial, including ACR response, onset of ACR20 response, HAQ-DI, and DAS28.

See the BEACON clinical trial design and additional results

Olumiant Safety Profile

This Olumiant safety data set includes over 2500 patients enrolled in 6 randomized, double-blind, placebo-controlled studies (three phase 2, three phase 3) and a long-term extension study. Patients were randomized to placebo (n=1070), Olumiant 2 mg (n=479), or higher dose which is not approved (n=997).

Common adverse events2

Common adverse events

*Includes acute sinusitis, acute tonsillitis, chronic tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, sinusitis, tonsillitis, tracheitis, and upper respiratory tract infection.

Includes eczema herpeticum, genital herpes, herpes simplex, ophthalmic herpes simplex, and oral herpes.

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

Patients in this data set were receiving background cDMARDs.

Adverse events of special interest2

Adverse events of special interest

*In the 0 to 52 week exposure population, most commonly reported serious infections were pneumonia, herpes zoster, and urinary tract infection.

§Although there were no TB events reported for placebo or Olumiant 2 mg in this time period, TB events were reported in patients receiving a higher dose, which is not approved.

Excluding TB.

Excluding non-melanoma skin cancer (NMSC).

Patients in this data set were receiving background cDMARDs.

Lilly is conducting long-term safety studies, including post-marketing studies, to continue to evaluate the safety of Olumiant. Certain adverse events, such as malignancy, require longer observation periods and larger patient exposure to ascertain risk.

Extended safety analyses—adverse events of special interest8-15

Extended safety analyses

The extended safety analyses of baricitinib include all patients with active RA (including nonindicated patient populations) exposed to any baricitinib dose (including non-approved doses). As of February 13, 2018, 3770 patients received baricitinib for 10,127 total PY.8 Of these, 2960 (78.5%) patients had ≥52 weeks and 2466 (65.4%) patients had ≥104 weeks of treatment with a maximum exposure of 2520 days.8 The majority of patients were exposed to a higher dose which is not approved.

Chart of extended safety analysis of adverse events of special interest for patients taking Olumiant

*Cases of disseminated tuberculosis were also reported.

Excludes tuberculosis.

Includes multidermatomal herpes zoster.

§Excluding non-melanoma skin cancer (NMSC).

Limitations of data analyses

Some patients do not qualify or choose not to enroll, and some are ineligible due to prior events, such as malignancies. Some patients discontinue from the extended study for a range of possible reasons, including AEs. Information on AEs is limited to the time that patients are taking the study drug and up to approximately 4 weeks after discontinuation; information on AEs that occur more than 4 weeks after discontinuation is often not available.

Patient numbers and total exposure vary across the extended study time points as a function of patients entering or leaving the extended study, and/or changing their dosing.

Rates are subject to change depending on the timing of the data analysis.

TB=tuberculosis; PY=patient years; RA=rheumatoid arthritis; IR per 100 PY=incidence rate per 100 patient years; DVT=deep venous thrombosis; PE=pulmonary embolism; IR=incidence rate.

Olumiant mechanism of action

Olumiant is a JAK inhibitor for the treatment of moderately to severely active RA for adult patients with an inadequate response to TNFis.

See how Olumiant works

ACR=American College of Rheumatology; ACR20=American College of Rheumatology 20% improvement criteria; HAQ-DI=Health Assessment Questionnaire-Disability Index; DAS28=Disease Activity Score 28.

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:
Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs, or with potent immunosuppressants, such as azathioprine and cyclosporine.

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. 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.
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 of ALT ≥5x upper limit of normal (ULN) and increases of AST ≥10x ULN were observed 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.


HYPERSENSITIVITY: Reactions such as angioedema, urticaria, and rash that may reflect drug sensitivity 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.

ADVERSE REACTIONS

Most common adverse reactions include: upper respiratory tract infections (16.3%, 11.7%), nausea (2.7%, 1.6%), herpes simplex (0.8%, 0.7%), and herpes zoster (1.0%, 0.4%) for Olumiant 2 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 severe renal impairment.


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

BA HCP ISI 09JUL2020