OLUMIANT® Long-Term Safety Profile Established Up to 9.3 Years in Integrated Analysis of More Than 3,700 Patients with Rheumatoid Arthritis
"Rheumatoid arthritis is a chronic inflammatory disease that requires long-term treatment to manage symptoms, including joint pain, swelling and tenderness, and if left uncontrolled, can be associated with significant morbidity complications," said Professor
OLUMIANT RA Safety Profile Remains Consistent Up to 9.3 Years
A pooled analysis across nine randomized studies and one long-term extension study evaluated the safety of OLUMIANT 4-mg and OLUMIANT 2-mg over time in 3,770 patients with RA, who were exposed to treatment for a total of 14,744 patient years of exposure. Participants had a median exposure of 4.6 years and a maximum exposure of 9.3 years.
Among those treated with OLUMIANT, the overall incidence rate of adverse events per 100 patient years of exposure was 22.6, and the incidence rate of serious adverse events was 7.4. Incidence rates remained stable over time across the 14,744 patient years of exposure. The incidence rate of serious infections was 2.58 per 100 patient years of exposure.
Adverse events of special interest included venous thromboembolic events (pulmonary embolism, incidence rate=0.26; deep vein thrombosis, incidence rate=0.35; deep vein thrombosis and/or pulmonary embolism, incidence rate=0.49) and major adverse cardiovascular events (incidence rate=0.51) within the range of incidence rates described in epidemiological studies in the general RA population. Incidence rates of safety events of special interest among those treated with OLUMIANT remained stable through exposures up to 9.3 years and were generally similar between the OLUMIANT 2-mg and 4-mg groups. In a subgroup of patients over 50 years old who had at least one cardiovascular risk factor (current smoker, hypertension, high-density lipoprotein cholesterol <40 mg/dL, diabetes, or arteriosclerotic cardiovascular disease), the incidence rate of major adverse cardiovascular events (MACE) was 0.77 per 100 patient years of exposure vs. 0.51 in the total study population.
In this study, age-adjusted incidence rates for malignancy (incidence rate=0.92) and mortality (incidence rate=0.6) for patients treated with OLUMIANT appear similar to the general
For methodology, see the full abstract on the ACR website.
Real-World Evidence Study Reinforces OLUMIANT 4-mg and 2-mg Safety Profile at 24-Weeks
A post-marketing surveillance study of 3,445 patients with RA in
Overall, 26% of patients (n=887) reported an adverse event and 4% of patients (n=122) reported a serious adverse event, with six deaths, none of which were related to deep vein thrombosis or pulmonary embolisms. Priority survey events included herpes zoster (3%, n=100), liver dysfunction (3%, n=100), serious infection (1.5%, n=51), anemia (1%, n=41), hyperlipidemia (1%, n=40), malignancy (0.3%, n=11), interstitial pneumonia (0.2%, n=8), MACE (0.1%, n=5) and venous thromboembolism (0.1%, n=3).
For methodology, see the full abstract on the ACR website.
"OLUMIANT has one of the largest and longest sets of available safety data in the JAK inhibitor class, spanning 19,000 total patient years of exposure, including almost 15,000 patient years in RA, over a period of over nine years across the clinical development program," said Lotus Mallbris, M.D., Ph.D., vice president of global immunology development and
OLUMIANT, a once-daily, oral JAK inhibitor was discovered by Incyte and licensed to Lilly. It is approved in the U.S. and more than 75 countries as a treatment for adults with moderate to severe rheumatoid arthritis and is approved in more than 50 countries, including the European Union and Japan, for the treatment of adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. Marketing authorization for the treatment of hospitalized patients with COVID-19 has been granted for OLUMIANT in multiple countries. The U.S. FDA-approved labeling for OLUMIANT includes a Boxed Warning for Serious Infections, Malignancy, and Thrombosis. See the full Prescribing Information here. Baricitinib is also being investigated in alopecia areata (AA), juvenile idiopathic arthritis (JIA) and systematic lupus erythematosus (SLE).
Indication and Usage for OLUMIANT (baricitinib) tablets (in
OLUMIANT® (baricitinib) 2 mg is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis 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 (DMARDs), 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 localized 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.
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.
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.
BA HCP ISI 09JUL2020
About Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease characterized by inflammation and progressive destruction of joints.1,2 More than 23 million people worldwide suffer from RA.3 Approximately three times as many women as men have the disease.5 Patients and physicians indicate there remains an important opportunity to improve patient care. Current treatment of RA includes the use of non-steroidal anti-inflammatory drugs, oral disease-modifying anti-rheumatic drugs such as methotrexate, and injectable biological response modifiers that target selected mediators implicated in the pathogenesis of RA.4
OLUMIANT® is a registered trademark owned or licensed by
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about OLUMIANT (baricitinib) as a treatment for patients with rheumatoid arthritis and as a possible treatment for other conditions and reflects
1. Klareskog L, Catrina AI, Paget S.
3. WHO Global Burden of Disease Report, (table 7, page 32) 2004, http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.
4. Hunter TM, et al. Rheumatol Int. 2017;37:1551–1557.
Marlo Scott; email@example.com; +1-317-407-8879 (Lilly media)
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