Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Effekt av Body Mass Index på effektivitet

Body mass index påverkade inte de övergripande förbättringarna i kliniska studier av baricitinib jämfört med placebo hos patienter med reumatoid artrit.

Information from the Summary of Product Characteristics

Body weight did not have a clinically relevant effect on the PK of baricitinib. The mean effects of intrinsic factors on PK parameters (AUC and Cmax) were generally within the inter-subject PK variability of BARI. Therefore, no dose adjustment is needed based on these patient factors.1

Efficacy by Baseline BMI From RA-BEACON and RA-BUILD

RA-BEACON is a phase 3 study that compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with RA and an inadequate response to at least one TNF inhibitor, who may also have had an inadequate response to one or more non-TNF inhibitor biologic DMARDs.2

Results in BARI 2 mg, BARI 4 mg, and Placebo Groups

BARI 2 mg treated and BARI 4 mg treated patients achieved greater improvements than placebo-treated patients in RA efficacy measures regardless of the baseline BMI tertiles of

  • <25

  • 25 to <30, and

  • 30.3

Results are presented in Table 1.

Table 1. RA-BUILD and RA-BEACON Efficacy Results by Baseline BMI3


Baseline BMI (kg/m2)

Baseline BMI (kg/m2)

Baseline BMI (kg/m2)

Baseline BMI (kg/m2)

Baseline BMI (kg/m2)

Baseline BMI (kg/m2)


BMI <25

BMI <25

BMI ≥25 and <30

BMI ≥25 and <30

BMI ≥30

BMI ≥30

At week 12

RA-BUILDa

RA-BEACONb

RA-BUILDa

RA-BEACONb

RA-BUILDa

RA-BEACONb

ACR20, n (%)

BARI 2 mg

52 (67.5%)

27 (55.1%)

51 (73.9%)

20 (51.3%)

47 (58.0%)

38 (44.2%)

BARI 4 mg

49 (65.3%)

27 (62.8%)

45 (67.2%)

39 (62.9%)

46 (54.1%)

32 (44.4%)

Placebo

34 (42.5%)

9 (23.1%)

26 (40.6%)

18 (30.0%)

30 (35.7%)

20 (26.3%)

ACR50, n (%)

BARI 2 mg

24 (31.2%)

11 (22.4%)

26 (37.7%)

10 (25.6%)

26 (32.1%)

14 (16.3%)

BARI 4 mg

30 (40.0%)

16 (37.2%)

25 (37.3%)

21 (33.9%)

21 (24.7%)

13 (18.1%)

Placebo

10 (12.5%)

4 (10.3%)

9 (14.1%)

4 (6.7%)

10 (11.9%)

6 (7.9%)

DAS28-hsCRPc, LSM Δ from baseline (SE)

BARI 2 mg

-1.92 (0.14)

-1.48 (0.18)

-1.91 (0.14)

-1.66 (0.22)

-1.68 (0.13)

-1.47 (0.13)

BARI 4 mg

-2.09 (0.14)

-2.26 (0.20)

-2.10 (0.14)

-1.95 (0.17)

-1.62 (0.13)

-1.46 (0.14)

Placebo

-1.09 (0.14)

-0.83 (0.21)

-1.01 (0.15)

-0.84 (0.18)

-1.11 (0.13)

-0.88 (0.14)

DAS28-hsCRP ≤3.2, n (%)

BARI 2 mg

28 (36.4%)

12 (24.5%)

26 (37.7%)

14 (35.9%)

27 (33.3%)

16 (18.6%)

BARI 4 mg

39 (52.0%)

20 (46.5%)

30 (44.8%)

22 (35.5%)

20 (23.5%)

14 (19.4%)

Placebo

14 (17.5%)

2 (5.1%)

10 (15.6%)

6 (10.0%)

15 (17.9%)

7 (9.2%)

SDAI ≤ 3.3, n (%)

BARI 2 mg

6 (7.8%)

0

9 (13.0%)

1 (2.6%)

6 (7.4%)

3 (3.5%)

BARI 4 mg

8 (10.7%)

2 (4.7%)

5 (7.5%)

5 (8.1%)

7 (8.2%)

2 (2.8%)

Placebo

0

0

1 (1.6%)

2 (3.3%)

1 (1.2%)

1 (1.3%)

HAQ-DIc, LSM Δ from baseline (SE)

BARI 2 mg

-0.47 (0.06)

-0.41 (0.07)

-0.58 (0.06)

-0.42 (0.09)

-0.53 (0.06)

-0.36 (0.05)

BARI 4 mg

-0.52 (0.06)

-0.41 (0.07)

-0.54 (0.06)

-0.56 (0.07)

-0.48 (0.06)

-0.32 (0.06)

Placebo

-0.31 (0.06)

-0.14 (0.08)

-0.31 (0.06)

-0.19 (0.07)

-0.32 (0.06)

-0.22 (0.06)

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology; BARI = baricitinib; BMI = body mass index; DAS28-hsCRP = Disease Activity Score - high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; SDAI = Simplified Disease Activity Index; Δ = change.

a Total N for each arm: BARI 2 mg = 229; BARI 4 mg = 227; placebo = 228.

b Total N for each arm: BARI 2 mg = 174; BARI 4 mg = 177; Placebo = 176.

c Modified last observation carried forward.

Efficacy by Baseline BMI From Pooled Analysis

A pooled post hoc analysis of 2 phase 3 clinical trials in patients with RA and inadequate response to csDMARDs assessed the effect of baseline BMI on the response of BARI treatment.4

The phase 3 clinical trials included in this analysis were 

  • RA-BEAM that compared BARI 4 mg vs placebo or adalimumab, with background MTX, in patients with inadequate response to MTX.5 

  • RA-BUILD that compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with inadequate response to csDMARDs.6

Results for BARI 4 mg and Placebo Groups

BARI 4 mg treated patients (n=714) achieved greater improvements than placebo treated patients (n=716) in RA efficacy measures regardless of the baseline BMI tertiles of

  • <22.9 lowest BMI

  • 22.9 to ≤30.7 middle BMI, and

  • >30.7 highest BMI.4

Results are presented in Table 2.

Table 2. RA-BEAM and RA-BUILD Pooled Analysis Efficacy Results by Baseline BMI7


Baseline BMI

At 12 weeks

Lowest BMI < 22.9

Middle BMI ≥22.9 to ≤30.7

Highest BMI >30.7

ACR20, n (%)

BARI 4 mg, (n=714)

160 (68.4%)

166 (68.0%)

152 (64.7%)

Placebo, (n=716)

90 (36.1%)

92 (40.4%)

104 (43.5%)

ACR50, n (%)

BARI 4 mg

103 (44.0%)

110 (45.1%)

81 (34.5%)

Placebo

36 (14.5%)

38 (16.7%)

37 (15.5%)

DAS28-hsCRPa LSM Δ from baseline (95% CI)

BARI 4 mg 

-2.6 (-2.80 to -2.30)

-2.2 (-2.37 to -1.95)

-2.0 (-2.20 to -1.83)

Placebo

-1.2 (-1.45 to -0.97)

-0.9 (-1.16 to -0.74)

-1.2 (-1.35 to -0.97)

CDAIa LSM Δ from baseline (95% CI)

BARI 4 mg

-24.1 (-26.63 to -21.61)

-21.5 (-23.73 to -19.30)

-21.3 (-23.19 to -19.34)

Placebo

-14.5 (-16.93 to -12.02)

-12.1 (-14.30 to -9.92)

-15.0 (-16.97 to -13.09)

SDAIa LSM Δ from baseline (95% CI)

BARI 4 mg

-25.8 (-28.35 to -23.16)

-22.6 (-24.92 to -20.34)

-22.3 (-24.29 to -20.33)

Placebo

-14.7 (-17.24 to -12.16)

-12.2 (-14.43 to -9.90)

-15.0 (-17.01 to -13.01)

HAQ-DIa LSM Δ from baseline (95% CI)

BARI 4 mg

-0.7 (-0.85 to -0.62)

-0.6 (-0.72 to -0.53)

-0.6 (-0.66 to -0.49)

Placebo

-0.4 (-0.51 to -0.28)

-0.3 (-0.41 to -0.22)

-0.4 (-0.46 to -0.29)

At 24 weeks

mTSS ≤0b, n (%)

BARI 4 mg

180 (81.1%)

180 (80.0%)

188 (85.5%)

Placebo

137 (60.4%)

155 (74.9%)

176 (83.8%)

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology; BARI = baricitinib; BMI = body mass index; CDAI = Clinical Disease Activity Index; DAS28-hsCRP = Disease Activity Score - high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; mTSS = modified Total Sharp Score; SDAI = Simplified Disease Activity Index; Δ = change.

a Modified last observation carried forward.

b No progression of structural damage.

References

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

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

4. Zerbini C, Muram D, Arora V, et al. Effect of BMI on baricitinib efficacy: pooled analysis from two phase 3 rheumatoid arthritis clinical trials [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/effect-of-bmi-on-baricitinib-efficacy-pooled-analysis-from-two-phase-3-rheumatoid-arthritis-clinical-trials/

5. 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

6. 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

7. Zerbini C, Muram D, Arora V, et al. Effect of BMI on baricitinib efficacy: pooled analysis from two phase 2 rheumatoid arthritis clinical trials. Poster presented at: American College of Rheumatology (ACR/ARHP) Annual Meeting; November 12-16, 2016; Washington, D.C.

Glossary

BARI = baricitinib

BMI = body mass index

csDMARD = conventional synthetic disease-modifying antirheumatic drug

DMARD = disease-modifying antirheumatic drug

MTX = methotrexate

PK = pharmacokinetics

RA = rheumatoid arthritis

TNF = tumor necrosis factor

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 M07 10


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