Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Samtidig användning av antitrombotiska medel

Vid kliniska studier av reumatoid artrit (RA) fick vissa patienter som behandlade med baricitinib samtidigt antitrombotisk terapi.

Description of Baricitinib Rheumatoid Arthritis Phase 3 Clinical Trials

Each of the 4 phase 3 studies in the clinical program evaluated a distinct treatment population of patients with moderate-to-severe RA.

  • RA-BUILD compared BARI 2 mg and 4 mg vs PBO, with background csDMARD therapy, in patients with inadequate response to csDMARDs.1

  • RA-BEACON compared BARI 2 mg and 4 mg vs PBO, with background csDMARD therapy, in patients with inadequate response to TNF inhibitors, other biologic DMARDs, or both.2

  • RA-BEAM compared BARI 4 mg vs PBO or adalimumab, with background MTX, in patients with inadequate response to MTX.3

  • RA-BEGIN compared BARI 4 mg monotherapy, MTX monotherapy, and BARI 4 mg plus MTX in patients who had limited or no prior treatment with MTX and were naïve to other DMARDs.4

The study population of DMARD-naïve patients from the RA-BEGIN study is not included in the approved label. However, the RA-BEGIN study is supportive for the target population of patients with an inadequate response to, or intolerance to, other DMARDs.5

Clinical Trial Program Criteria

Concomitant use of anticoagulant treatments was not prohibited in the phase 3 clinical studies.6 Concomitant use of anticoagulant treatments are not included in the drug-drug interaction information specific to BARI, and drug-drug interaction studies were not performed specifically for BARI and any anticoagulant therapies.7

Patients were excluded from the phase 3 trials if they had

  • history or presence of cardiovascular, respiratory, or hematological disorders or any other serious or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data, and

  • any major surgery within 8 weeks prior to study entry or would require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the patient.6

Drug-Drug Interactions

Antithrombotic Treatments

Concomitant use of antithrombotic treatments are not included in the drug-drug interaction information specific to BARI, and drug-drug interaction studies were not performed specifically for BARI and any anticoagulant or antiplatelet agents.7

Drug-Drug Interaction Pharmacology Studies

Based on clinical pharmacology studies, no clinically relevant effects on BARI pharmacokinetics occurred with the co-administration of BARI and

  • a CYP3A inhibitor

  • a CYP2C19/CYP2C9/CYP3A inhibitor

  • a CYP3A inducer, or

  • a Pgp inhibitor.7

Co-administration of BARI with either a CYP3A substrate or a Pgp substrate resulted in no clinically relevant effects on the pharmacokinetics of these drugs.7

References

1. Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study [published correction appears in Ann Rheum Dis. 2017;76(9):1634. http://dx.doi.org/10.1136/annrheumdis-2016-210094corr1 ]. Ann Rheum Dis. 2017;76(1):88-95. http://dx.doi.org/10.1136/annrheumdis-2016-210094

2. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-1252. http://dx.doi.org/10.1056/NEJMoa1507247

3. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652-662. http://dx.doi.org/10.1056/NEJMoa1608345

4. Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506-517. http://dx.doi.org/10.1002/art.39953

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

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

7. Payne C, Zhang X, Shahri N, et al. Evaluation of Potential Drug-Drug Interactions With Baricitinib. Poster presented at: the Annual Meeting of the American Association of Pharmaceutical Scientists (AAPS); October 25-29, 2015; Orlando, FL.

8. DO NOT USE - Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying anti-rheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506-517. http://dx.doi.org/10.1002/art.39953

Glossary

BARI = baricitinib

BMI = body mass index

COX-2 = cyclooxygenase-2

CYP = cytochrome P450

csDMARD = conventional synthetic disease-modifying antirheumatic drug

DMARD = disease-modifying antirheumatic drug

DVT = deep vein thrombosis

Lilly = Eli Lilly and Company

MTX = methotrexate

PBO = placebo

PE = pulmonary embolism

Pgp = P-glycoprotein

RA = rheumatoid arthritis

VTE = venous thromboembolism

Appendix

Table 1. Concomitant Aspirin Use in Baricitinib Rheumatoid Arthritis Phase 3 Clinical Trials6







Concomitant ASA Use by ATCa, n (%)

Study

n

Antithrombotic

Analgesic

RA-BEACONb2(N=527)

BARI 2 mg

174

20 (11.5)

0

BARI 4 mg

177

24 (13.6)

1 (0.6)

PBO

176

21 (11.9)

0

RA-BUILDc1 (N=684)

BARI 2 mg

229

19 (8.3)

1 (0.4)

BARI 4 mg

227

20 (8.8)

1 (0.4)

PBO

228

16 (7.0)

1 (0.4)

RA-BEAMd3 (N=1305)

BARI 4 mg

487

34 (7.0)

0

Adalimumab

330

19 (5.8)

1 (0.3)

PBO

488

22 (4.5)

1 (0.2)

RA-BEGINe8 (N=584)

BARI 4 mg

159

13 (8.2)

1 (0.6)

BARI 4 mg + MTX

215

11 (5.1)

0

MTX

210

10 (4.8)

0

Abbreviations: ASA = acetylsalicylic acid; ATC = Anatomical Therapeutic Chemical classification system; BARI = baricitinib; MTX = methotrexate; PBO = placebo; RA = rheumatoid arthritis.

a Dose or dose range was not collected.

b RA-BEACON compared BARI 2 mg and 4 mg vs PBO, with background csDMARD therapy, in patients with inadequate response to TNF inhibitors, other biologic DMARDs, or both.

c RA-BUILD compared BARI 2 mg and 4 mg vs PBO, with background csDMARD therapy, in patients with inadequate response to cDMARDs.

d RA-BEAM compared BARI 4 mg vs PBO or adalimumab, with background MTX, in patients with inadequate response to MTX.

e RA-BEGIN compared BARI 4 mg monotherapy, MTX monotherapy, and BARI 4 mg plus MTX in patients who had limited or no prior treatment with MTX and were naïve to other DMARDs.

Table 2. Concomitant Antithrombotic Therapies Other Than Aspirin Administered for Rheumatoid Arthritis in Study RA-BUILD6

ATC Level 2 Term (Preferred Name)

Placebo (N=228)
n (%)

BARI 2 mg (N=229)
n (%)

BARI 4 mg (N=227)
n (%)

Antithrombotic Agents

23 (10.1)

25 (10.9)

26 (11.5)

Cilostazol

0

0

1 (0.4)

Clopidogrel

2 (0.9)

1 (0.4)

1 (0.4)

Enoxaparin

5 (2.2)

0

1 (0.4)

Heparinoid

0

1 (0.4)

Mesoglycan

0

0

1 (0.4)

Rivaroxaban

0

0

1 (0.4)

Warfarin

0

2 (0.9)

1 (0.4)

Acenocoumarol

1 (0.4)

0

0

Fondaparinux

0

1 (0.4)

0

Magnyl

0

2 (0.9)

0

Phenprocoumon

1 (0.4)

0

0

Ticagrelor

1 (0.4)

0

0

Abbreviations: ATC = Anatomical Therapeutic Chemical classification system; BARI = baricitinib.

Table 3. Concomitant Antithrombotic Therapies Other Than Aspirin Administered for Rheumatoid Arthritis in Study RA-BEACON6

ATC Level 2 Term (Preferred Name)

Placebo (N=176)
n (%)

BARI 2 mg (N=174)
n (%)

BARI 4 mg (N=177)
n (%)

Antithrombotic Agents

30 (17.0)

25 (14.4)

33 (18.6)

Clopidogrel

6 (3.4)

2 (1.1)

6 (3.4)

Warfarin

5 (2.8)

2 (1.1)

5 (2.8)

Phenprocoumon

0

1 (0.6)

2 (1.1)

Enoxaparin

1 (0.6)

2 (1.1)

1 (0.6)

Fondaparinux

0

0

1 (0.6)

Heparin

1 (0.6)

0

1 (0.6)

Acenocoumarol

0

1 (0.6)

0

Certoparin Sodium

0

1 (0.6)

0

Dabigatran

2 (1.1)

1 (0.6)

0

Dalteparin

0

1 (0.6)

0

Prasugrel

1 (0.6)

0

0

Abbreviation: ATC = Anatomical Therapeutic Chemical classification system; BARI = baricitinib.

Table 4. Concomitant Antithrombotic Therapies Other Than Aspirin Administered for Rheumatoid Arthritis in Study RA BEAM6

ATC Level 2 Term (Preferred Name)

Placebo (N=488)
n (%)

BARI 4 mg (N=487)
n (%)

ADA (N=330)
n (%)

Antithrombotic Agents

35 (7.2)

47 (9.7)

28 (8.5)

Warfarin

4 (0.8)

6 (1.2)

0

Enoxaparin

4 (0.8)

4 (0.8)

2 (0.6)

Clopidogrel

3 (0.6)

3 (0.6)

3 (0.9)

Nadroparin

0

2 (0.4)

0

Rivaroxaban

0

2 (0.4)

0

Acenocoumarol

1 (0.2)

1 (0.2)

2 (0.6)

Dipyridamole

0

1 (0.2)

0

Heparin

2 (0.4)

1 (0.2)

0

Prasugrel

0

1 (0.2)

0

Sulodexide

0

1 (0.2)

1 (0.3)

Ticagrelor

0

1 (0.2)

0

Tinzaparin

0

1 (0.2)

0

Cilostazol

1 (0.2)

0

0

Dalteparin

0

0

1 (0.3)

Heparinoid

0

0

1 (0.3)

Magnyl

0

0

1 (0.3)

Paynocil

0

0

1 (0.3)

Streptokinase

0

0

1 (0.3)

Ticlopidine

0

0

1 (0.3)

Abbreviations: ADA = adalimumab; ATC = Anatomical Therapeutic Chemical classification system; BARI = baricitinib.

Table 5. Concomitant Antithrombotic Therapies Other Than Aspirin Administered for Rheumatoid Arthritis in Study RA BEGIN6

ATC Level 2 Term (Preferred Name)

MTX (N=210)
n (%)

BARI 4 mg (N=159)
n (%)

BARI 4 mg + MTX (N=215)
n (%)

Antithrombotic Agents

15 (7.1)

15 (9.4)

14 (6.5)

Enoxaparin

1 (0.5)

0

3 (1.4)

Rivaroxaban

0

0

2 (0.9)

Acenocoumarol

0

0

1 (0.5)

Alteplase

0

0

1 (0.5)

Clopidogrel

1 (0.5)

2 (1.3)

1 (0.5)

Heparin

2 (1.0)

1 (0.6)

1 (0.5)

Warfarin

0

0

1 (0.5

Magnyl

0

1 (0.6)

0

Phenprocoumon

1 (0.5)

0

0

Ticagrelor

0

1 (0.6)

0

Abbreviations: ATC = Anatomical Therapeutic Chemical classification system; BARI = baricitinib; MTX = methotrexate.

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 31


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