Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Lipid Effekter

Baricitinib var associerat med ökade lipidparametrar i fas 3 klinisk utvecklingsprogram för reumatoid artrit (RA).

Treatment-Emergent Adverse Events Related to Hyperlipidemia

In controlled studies, for up to 16 weeks hypercholesterolaemia was very commonly reported (≥ 1/10) and hypertriglyceridaemia was uncommonly reported (≥ 1/1,000).1

4-Study and 6-Study Datasets

Through up to 16 weeks, a statistically significantly larger proportion of patients had a TEAE related to a hyperlipidemia event for BARI 4 mg compared to

  • BARI 2 mg (7.7% vs 4.2%, respectively; p=.020), and

  • placebo (6.9% vs 3.5%, respectively, p=.001).2

All BARI RA Dataset

The All BARI RA integrated safety dataset included 3492 patients who received BARI at a variety of doses for 7860 total patient-years of exposure from 1 phase 1, 3 phase 2, and 5 phase 3 studies. The analysis covered all exposure time points including after rescue or changes in study treatment through April 1, 2017.3

In the All BARI RA dataset, in patients treated with BARI, the MedDRA preferred terms,

  • hypercholesterolaemia was reported in 185 patients (5.3%; 2.35 EAIR), and

  • hyperlipidaemia was reported in 131 patients (3.8%; 1.67 EAIR).2

None of these events were considered serious; 1 hyperlipidaemia event led to permanent discontinuation of study drug.2

Changes in Lipid Analytes and Lipid Particle Size

Changes in Lipid Analytes

Baricitinib treatment was associated with dose-dependent increases in lipid parameters including total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol. There was no change in the LDL/HDL ratio. Elevations were observed at 12 weeks and remained stable thereafter at a higher value than baseline including in the long-term extension study. In controlled studies, for up to 16 weeks, the following rates were observed for baricitinib vs. placebo:

  • Increased total cholesterol ≥ 5.17 mmol/L: 49.1 % vs.15.8 %, respectively

  • Increased LDL cholesterol ≥ 3.36 mmol/L: 33.6 % vs. 10.3 %, respectively

  • Increased HDL cholesterol ≥ 1.55 mmol/L: 42.7 % vs. 13.8 %, respectively

  • Increased triglycerides ≥ 5.65 mmol/L: 0.4 % vs. 0.5 %, respectively1

In studies which included both doses, a dose-relationship was observed with increased total cholesterol ≥ 5.17 mmol/L reported in 48.8 %, 34.7 % and 17.8 % of patients up to 16 weeks in the 4 mg, 2 mg and placebo groups, respectively.1

Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy.1

Compared to placebo, treatment with BARI 2 mg and BARI 4 mg was associated with statistically significant percent increases from baseline through week 24 in

  • total cholesterol

  • LDL-C, and

  • HDL-C (p≤.001 for all).4

Compared to placebo, treatment with BARI 4 mg was also associated with statistically significant percent increases from baseline through week 24 in triglycerides (p≤.001).4

The lipid elevations plateaued after week 12. The mean LDL-C/HDL-C ratio remained stable.4

Changes in Lipid Particle Size

In RA-BEAM, the NMR lipoprotein profile revealed similar changes for BARI and ADA treatment groups relative to the placebo group. Compared to placebo, BARI had statistically significant

  • increases in

    • total LDL (p≤.05) and large LDL (p≤.001) mean particle number, and

    • total HDL (p≤.001) and all subfractions of HDL (p≤.05) mean particle number, and

  • decreases in small, medium small, and very small LDL (p≤.01 for all) mean particle numbers.4

Compared to placebo, BARI had statistically significant

  • increases in LDL (p≤.001) and VLDL (p≤.01) mean particle size, and

  • modest decrease in HDL (p≤.05) mean particle size.4

Effect of Statins in Combination With Baricitinib on Lipid Analytes

Twenty-five patients receiving BARI 2 mg and 58 patients receiving BARI 4 mg initiated statin therapy after starting BARI. The effects of statin therapy were comparable between the BARI groups and placebo group (n=20) for

  • LDL-C

  • total cholesterol, and

  • triglycerides.4

Monitoring and Management related to Lipid Parameters

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

Therapeutic Indication

Baricitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. Baricitinib may be used as monotherapy or in combination with methotrexate.1

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. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 6 years: an updated integrated safety analysis. Poster presented at: Annual Meeting of the American College of Rheumatology (ACR); October 20-24, 2018; Chicago, IL.

4. Taylor PC, Kremer JM, Emery P, et al. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018;77(7):988-995. http://dx.doi.org/10.1136/annrheumdis-2017-212461

Glossary

ADA = adalimumab

BARI = baricitinib

EAIR = exposure-adjusted incidence rate

HDL = high-density lipoprotein

HDL-C = high-density lipoprotein cholesterol

LDL = low-density lipoprotein

LDL-C = low-density lipoprotein cholesterol

MedDRA = Medical Dictionary for Regulatory Activities

NMR = nuclear magnetic resonance

RA = rheumatoid arthritis

TEAE = treatment-emergent adverse event

VLDL = very low-density lipoprotein

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 2018 M06 01


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