Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Effektivitet och säkerhet hos patienter med komorbida kardiovaskulära sjukdomar

Effekt och säkerhet av baricitinib 4mg hos patienter med måttlig till svår reumatoid artrit och komorbida kardiovaskulära sjukdomar liknar den totala populationen.

Information from the label

Dose dependent increases in blood lipid parameters were reported in patients treated with baricitinib compared to placebo. Elevations in LDL cholesterol decreased to pre- treatment levels in response to statin therapy. Lipid parameters should be assessed approximately 12 weeks following initiation of baricitinib therapy and thereafter patients should be managed according to international clinical guidelines for hyperlipidaemia. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.1

Exclusion Criteria in the Phase 3 Clinical Trials

In the 4 phase 3 clinical trials, RA-BEGIN, RA-BEAM, RA-BUILD, and RA-BEACON, exclusion criteria related to CV conditions included 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, or

  • have experienced any of the following within 12 weeks of study entry

    • myocardial infarction

    • unstable ischemic heart disease

    • stroke, or

    • have New York Heart Association stage IV heart failure.2

Post Hoc Analyses of the Effects of Comorbid Cardiovascular Conditions in Patients Treated With Baricitinib

Study Design

A post hoc analyses consisting of data from 3 phase 2 studies and 2 phase 3 studies evaluated the effects of various comorbidities, including CV conditions, on efficacy and safety outcomes in patients treated with BARI.

  • Terms for CV conditions included acute myocardial infarction, blood cholesterol increased, blood glucose abnormal, blood glucose increased, cerebral infarction, cerebrovascular accident, coronary artery bypass, diabetes mellitus, diabetes mellitus inadequate control, diabetic ketoacidosis, essential hypertension, gestational diabetes, glucose tolerance impaired, hypercholesterolaemia, hyperglycaemia, hyperlipidaemia, hypertension, hypertensive cardiomyopathy, hypertensive heart disease, intermittent claudication, ischaemic stroke, labile hypertension, lacunar infarction, low-density lipoprotein increased, myocardial infarction, peripheralarterial occlusive disease, peripheral artery stenosis, subarachnoid haemorrhage, subdural haematoma, systolic hypertension, and transient ischaemic attack.3

Patient Disposition

Patients with an inadequate response to csDMARD receiving BARI 4 mg or PBO were included in the analyses. Overall, 1684 patients were included in the efficacy analyses (BARI 4 mg, n=803; PBO, n=881) and 1683 patients were included in the safety analyses (BARI 4 mg, n=802; PBO, n=881).

  • Of these, 350 patients taking BARI and 381 patients taking PBO had comorbid CV conditions at baseline.

Efficacy Outcomes and Results

At week 12, efficacy outcomes included

  • ACR20

  • ACR50

  • DAS28-hsCRP ≤3.2, and

  • change from baseline in HAQ-DI.3

Patients with comorbid CV conditions had improvements across efficacy measures that were consistent with those observed in the overall patient population (Table 1).3

Improvements in the efficacy outcomes were higher for BARI 4 mg compared to PBO in patients with comorbid CV conditions (Table 1).3

Safety Outcomes and Results

At week 16, safety outcomes included

  • TEAEs

  • SAEs

    • discontinuations due to adverse events, and

    • deaths.3

Table 1 summarizes the incidence of adverse events in patients taking BARI 4 mg compared to PBO in the overall population and in patients with comorbid CV conditions. The safety results for patients with comorbid CV conditions were consistent with the overall population.3

In patients with comorbid CV conditions, the incidence of TEAEs, SAEs, discontinuations due to adverse events, and deaths were similar between BARI 4 mg and PBO.3

Table 1. Comparison of Key Efficacy and Safety Outcomes in Patients With Previous Cardiovascular Conditions3,4


Overall Population

Patients With CV Conditions

BARI 4 mg
(N=803)

Placebo
(N=881)

BARI 4 mg
(N=350)

Placebo
(N=381)

Efficacy Outcomes At Week 12

ACR20, n (%)a

542 (67.5)

345 (39.2)

239 (68.3)

155 (40.7)

ACR50, n (%)a

330 (41.1)

127 (14.4)

143 (40.9)

55 (14.4)

DAS28-hsCPR ≤3.2, n (%)b

352 (43.8)

146 (16.6)

157 (44.9)

60 (15.7)

ΔHAQ-DI, N-obs (LSM) [SE]b

792 (-0.53) [0.03]

868 (-0.25) [0.03]

347 (-0.54) [0.04]

374 (-0.27) [0.04]

Safety Outcomes At Week 16

Any TEAE, n (%) [EAIR]

495 (61.7) [210]

494 (56.1) [200]

227 (64.9) [221]

228 (59.8) [212]

Serious AE, n (%) [EAIR]

25 (3.1) [10.6]

31 (3.5) [12.6]

14 (4.0) [13.6]

16 (4.2) [14.9]

Discontinuation due to AEs, n (%) [EAIR]

25 (3.1) [10.6]

24 (2.7) [9.7]

14 (4.0) [13.6]

12 (3.1) [11.1]

Deaths, n (%) [EAIR]

0 (0) [0.0]

1 (0.1) [0.4]c

0 (0) [0.0]

1 (0.3) [0.9]c

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology 20 Response criteria; ACR50 = 50% improvement in American College of Rheumatology 50 Response criteria; AE = adverse events; BARI = baricitinib; CV = cardiovascular; DAS28-hsCRP = disease activity score for 28-joint count using high-sensitivity C-reactive protein; HAQ-DI = health assessment questionnaire-disability index; LSM = least square means; mLOCF = modified last observation carried forward; N = number of patients in treatment arm; n = number of patients with response; NA = not applicable; N-obs = number of patients in the analyses; NRI = nonresponder imputation; TEAE= treatment-emergent adverse event.

Note: Terms for cardiovascular conditions included acute myocardial infarction, blood cholesterol increased, blood glucose abnormal, blood glucose increased, cerebral infarction,cerebrovascular accident, coronary artery bypass, diabetes mellitus, diabetes mellitus inadequate control, diabetic ketoacidosis, essential hypertension, gestational diabetes, glucose tolerance impaired, hypercholesterolaemia, hyperglycaemia,hyperlipidaemia, hypertension, hypertensive cardiomyopathy, hypertensive heart disease, intermittent claudication, ischaemic stroke, labile hypertension, lacunar infarction, low-density lipoprotein increased, myocardial infarction, peripheralarterial occlusive disease, peripheral artery stenosis, subarachnoid haemorrhage, subdural haematoma, systolic hypertension and transient ischaemic attack.

a Data calculated as NRI.

b Data calculated as mLOCF.

c One death occurred in a patient receiving placebo; this patient had depression, osteoporosis and a cardiovascular disorder.

Detailed Information

Summary of Product Characteristics

References

1. Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. Combe B, Balsa A, Sarzi-Puttini P, et al. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019;[Epub ahead of print]. http://dx.doi.org/10.1136/annrheumdis-2018-214261

4. Combe B, Balsa A, Sarzi-Puttini P, et al. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib [abstract]. Ann Rheum Dis. 2017;76(suppl 2). http://dx.doi.org/10.1136/annrheumdis-2017-eular.2227

Glossary

ACR = American College of Rheumatology

ACR20 = 20% improvement in American College of Rheumatology criteria

ACR50 = 50% improvement in American College of Rheumatology criteria

BARI = baricitinib

csDMARD = conventional synthetic disease-modifying antirheumatic drug

CV = cardiovascular

DAS28-hsCRP = Disease Activity Score based on high-sensitivity C-reactive protein

HAQ-DI = Health Assessment Questionnaire-Disability Index

PBO = placebo

RA = rheumatoid Arthritis

SAE = serious adverse event

TEAE = treatment-emergent adverse event

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2019 M05 15

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