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Olumiant ® (baricitinib) tabletter
Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska
Olumiant® (baricitinib): Allvarliga Hjärt- Kärlbiverkningar
I det kliniska utvecklingsprogrammet för baricitinib var behandling med BARI hos patienter med måttlig till svår aktiv RA inte förknippad med en ökad risk för allvarliga hjärt och kärlbiverkningar.
Incidence of Cardiovascular Events in Baricitinib Clinical Trials
Cardiovascular Risk in Patients With Rheumatoid Arthritis
An assessment of CV events was incorporated into the BARI phase 3 clinical development program as an event of interest.
Exclusion Criteria Related to Cardiovascular Events in the Baricitinib Rheumatoid Arthritis Clinical Development Program
In the 4 phase 3 clinical trials, RA-BEGIN, RA-BEAM, RA-BUILD, and RA-BEACON, eligibility criteria relating to CV events excluded patients who
- have screening electrocardiogram abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study, such as Fridericia’s corrected QT interval >500 milliseconds
- within 12 weeks of study entry have experienced
- unstable ischemic heart disease
- stroke, or
- have New York Heart Association stage IV heart failure.3
Cardiovascular Event Adjudication Process in Rheumatoid Arthritis Clinical Trials
An independent, external CEC was established to adjudicate potential CV adverse events for the BARI phase 3 clinical studies. The CEC remained blinded to treatment assignments and assessed each potential event individually.3
Potential CV events were identified to be sent for adjudication
- by the investigator indicating that a potential event occurred, or
- by sponsor and independent CEC review of SAE and TEAE MedDRA preferred terms according to a prespecified list to ensure that potential CV events that qualified for adjudication were sent for review.3
Positively adjudicated CV events were categorized as either
All cases of death, regardless of the investigator’s assessment as to the cause of death, were also sent for adjudication.3
Integrated Datasets Used to Evaluate Major Adverse Cardiovascular Events in Rheumatoid Arthritis Clinical Trials
The integrated datasets used to evaluate cases of MACE are described in more detail in . The exposure information, including median, maximum and total PYE, and cut-off date described in the table is applicable to the data presented below unless otherwise specified.
7-Study Placebo-Controlled Dataset
Studies: JADC, JADA, JADN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BALANCE
Compares BARI 4 mg vs placebo
Includes patients with RA from 3 phase 2 and 4 phase 3 studies who were randomized to
Patients in the placebo group could have been taking
Evaluation time periods included
BARI 2 mg Analysis Set
BARI 2 mg data is derived from 4 studies in which both BARI 2 mg (N=479, [exposure through 24 weeks: PYE=185.8, median exposure=168 days, maximum exposure=197 days]) and BARI 4 mg were options during randomization (JADA, JADN, RA-BUILD, RA-BEACON).
4-Study Extended Dataset
Studies: JADA, JADN, RA-BUILD, RA-BEACON, RA-BEYOND (extension)
Compares BARI 4 mg vs BARI 2 mg including extended evaluations
Includes patients with RA from 2 phase 2 and 2 phase 3 studies and any further exposure for those patients in the phase 3 extension study, RA-BEYOND, who were randomized to
Evaluation time period included randomization through last available observation incorporating extension data through 01 September 2019 unless otherwise specified.
All BARI RA Dataset
Studies: JADB, JADC, JADA, JADN, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BALANCE, RA-BEYOND (extension)
No between-group comparisons
Includes patients with RA (N=3770, PYE=13,148, median exposure=4.2 yrs, maximum exposure=8.4 yrs) from 1 phase 1, 3 phase 2, 5 phase 3 studies, and 1 phase 3 extension study who received BARI at a variety of doses, including
Patients had to have received at least 1 dose of BARI and could have received different doses throughout the trials.
Evaluation time period is all exposure time points including after rescue or changes in study drug through 01 September 2019 unless otherwise specified.
Abbreviations: BARI = baricitinib; DMARD = disease-modifying antirheumatic drug; MTX = methotrexate; PYE = patient-years of exposure; QD = once daily; RA = rheumatoid arthritis.
aPatients with renal function impairment who were randomized to BARI 4 mg, but treated with the 2-mg dose were analyzed in the BARI 4-mg group.
Incidence of Major Adverse Cardiovascular Events in the Baricitinib Rheumatoid Arthritis Clinical Development Program
Incidence rates were calculated as the number of patients with an event per 100 patient-years of exposure time, with exposure censored at time of event.6
7-Study Placebo-Controlled Dataset
In the combined 7-study dataset up to week 24, the number of patients with at least 1 positively adjudicated MACE was
- 3 (IR=0.7) in the BARI 4-mg group
- 0 in the BARI 2-mg group, and
- 2 (IR=0.5) in the placebo group.6
4-Study Extended Dataset
In the combined 4-study extended dataset, the number of patients with at least 1 positively adjudicated MACE was
- 3 (0.7%; EAIR=0.40) in the BARI 2-mg group, and
- 2 (0.5%; EAIR=0.29) in the BARI 4-mg group.3
All BARI RA Dataset
In the All BARI RA dataset, there were 63 MACE across all BARI doses and exposure durations. The incidence rate was 0.5 events per 100 PYE.5
displays the incidence rate for patients in the All BARI RA dataset with positively adjudicated MACE overall and by 12-month intervals. The rate of MACE does not appear to increase with duration of BARI exposure.7
1Kume K, Amano K, Yamada S. Tofacitinib improves arterial stiffness with methotrexate-resistant active rheumatoid arthritis. A cohort study [abstract]. Ann Rheum Dis. 2014;73(suppl 2):961. European League Against Rheumatism abstract AB0463. http://dx.doi.org/10.1136/annrheumdis-2014-eular.1019
2Sen D, Gonzalez-Mayda M, Brasington RD, Jr. Cardiovascular disease in rheumatoid arthritis. Rheum Dis Clin North Am. 2014;40(1):27-49. http://dx.doi.org/10.1016/j.rdc.2013.10.005
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Weinblatt M, Taylor PC, Burmester GR, et al. Cardiovascular safety – update from up to 6 years of treatment with baricitinib in rheumatoid arthritis clinical trials [abstract]. Arthritis Rheumatol. 2018;70(suppl 10):2815. https://acrabstracts.org/abstract/cardiovascular-safety-update-from-up-to-6-years-of-treatment-with-baricitinib-in-rheumatoid-arthritis-clinical-trials/
5Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis. Ann Rheum Dis. 2020;79(suppl 1):638. European League Against Rheumatism abstract FRI0123. https://ard.bmj.com/content/79/Suppl_1/642.1
6Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020;2(6):E347-E357. https://doi.org/10.1016/S2665-9913(20)30032-1
7Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis. Poster presented at: European League Against Rheumatism Virtual Congress; June 3-6, 2020.
BARI = baricitinib
CEC = Clinical Endpoint Committee
CV = cardiovascular
EAIR = exposure-adjusted incidence rate
IR = incidence rate
IV = intravenous
MACE = major adverse cardiovascular event
MedDRA = Medical Dictionary for Regulatory Activities
MI = myocardial infarction
PYE = patient-years of exposure
RA = rheumatoid arthritis
SAE = serious adverse event
TEAE = treatment-emergent adverse event
Datum fӧr senaste ӧversyn May 31, 2019