Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Effekt hos äldre subpopulation vid reumatoid artrit

I en post-hoc-analys av två poolade fas 3 RA-kliniska prövningar påverkade inte ålder effekten av baricitinib; dock rapporterades fler biverkningar hos äldre.

Post Hoc Subgroup Analysis of Pooled RA-BEAM and RA-BUILD: Effect of Age on Efficacy and Safety

Overview of Pooled Analysis

A post hoc analysis of data from RA-BEAM and RA-BUILD was conducted to evaluate the efficacy and safety of using BARI in the elderly subpopulation, defined as patients 65 years or older. Combined data from both trials provided an overall sample of

  • 714 patients in the BARI 4-mg group, and

  • 716 patients in the placebo group.1

Efficacy and safety data are presented for patients aged <50, ≥50 and <65 years, and ≥65 years.1

Efficacy Results

Greater numerical improvements were seen for the efficacy endpoints in the BARI 4-mg group compared to the placebo group consistently across all age groups (Table 1).1

Table 1. Efficacy Outcomes in the Elderly Population Compared to Younger Patients at Week 24 in RA-BUILD and RA-BEAM1


Baricitinib 4 mg

<50 years

(n=259)

Baricitinib 4 mg

50 and <65 years
(n=319)

Baricitinib 4 mg

65 years
(n=136)

Placebo

<50 years
(n=254)

Placebo

50 and <65 years
(n=349)

Placebo

65 years
(n=113)

ACR20, %

Week 12

69

66

68

37

41

43

Week 24

76

67

71

35

40

40

ACR50, %

Week 12

41

41

42

15

16

14

Week 24

54

45

47

19

20

24

ACR70, %

Week 12

18

17

24

5

4

4

Week 24

34

24

27

7

 9

8

CDAI, week 24, %

LDA (≤10)

52

48

53

19

23

27

Remission (≤2.8)

16

15

18

3

5

4

SDAI, week 24, %

LDA (≤11)

54

49

53

19

24

27

Remission (≤3.3)

17

14

18

3

4

3

Abbreviations: ACR20 = American College of Rheumatology 20% response criteria; ACR50 = American College of Rheumatology 50% response criteria; ACR70 = American College of Rheumatology 70% response criteria; CDAI = Clinical Disease Activity Index; LDA = low disease activity; SDAI = Simplified Disease Activity Index.

Safety Results

In both the BARI 4-mg and placebo groups, elderly patients had more AEs, serious AEs, and discontinuations due to AEs at week 24.1

Serious AEs requiring hospitalization were reported in

  • 1 patient due to thrombophlebitis in the BARI 4-mg <50-year age group, and

  • 6 patients due to fractures related to falls with 2 in the ≥65-year age group.1

None of these patients discontinued the study, and all of these events resolved.1

There were 4 deaths in patients ≥50 years of age due to

  • subarachnoid hemorrhage and renal failure in the placebo ≥50 and <65 group (n=2)

  • circulatory failure in the BARI 4-mg ≥50 and <65 group (n=1), and

  • pneumonia in the BARI 4-mg elderly group (n=1).1

Post Hoc Subgroup Analysis of Pooled RA-BEAM and RA-BUILD: Effect of Baseline Demographics on Efficacy

Overview of Post Hoc Analysis

This post hoc analysis assessed the effect of baseline demographics, including age, on the response to BARI treatment in patients with RA and an inadequate response to prior csDMARDs.2

Data was pooled from 2 phase 3 double-blind, randomized controlled trials for

  • 714 patients who received BARI 4 mg, and

  • 716 patients who received placebo.2

Efficacy Results

Patients in the BARI 4-mg group had improved efficacy compared with patients in the placebo group regardless of age group (Table 2). None of the reported baseline demographic characteristics had a substantial effect on the reported efficacy outcomes.2

 

Table 2. Clinical Efficacy After 12 Weeks by Baseline Demographic Subgroups in RA-BEAM and RA-BUILD2


ACR20 Response
n/group n (%)

PBO
N=716

ACR20 Response
n/group n (%)

BARI 4 mga
N=714

Change from Baseline in DAS28-hsCRP
LSM (SE)

PBO
N=716

Change from Baseline in DAS28-hsCRP
LSM (SE)

BARI 4 mga
N=714

Patients Achieving SDAI ≤11
n/group n (%)

PBO
N=716

Patients Achieving SDAI ≤11
n/group n (%)

BARI 4 mga
N=714

Age group (years)

<65

237/603
39.3%

387/578
67.0%

-1.0 (0.05)

-2.1 (0.05)

102/603
16.9%

221/578
38.2%

65

49/113
43.4%

92/136
67.6%

-1.2 (0.11)

-2.4 (0.10)

20/113
17.7%

63/136
46.3%

75

4/14

28.6%

16/22

72.7%

0.2 (0.67)

-1.6 (0.59)

2/14

14.3%

10/22

45.5%

Abbreviations: ACR20 = American College of Rheumatology 20% response criteria; BARI = baricitinib; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; LSM = least squares mean; PBO = placebo; SDAI = Simplified Disease Activity Index.

a Only the baricitinib 4-mg dose was included in the subgroup analysis although baricitinib 2 mg was evaluated in RA-BUILD.

Safety Results

The proportions of patients ≥65 years of age and <65 years of age who reported AEs or SAEs or discontinued from the study due to an AE were similar in the BARI 4-mg and placebo groups.2

Pooled Analysis of Phase 2 and Phase 3 Studies: Effect of Baseline Demographics on Efficacy

Effect of Age on Efficacy of Baricitinib

Overview of Pooled Analysis

Demographic subgroups were also evaluated using pooled data from

  • 3 phase 2 studies

    • JADC

    • JADA, and

    • JADN, and

  • 2 phase 3 studies, RA-BEAM and RA-BUILD.3

Patients included in this analysis were

  • inadequate responders to csDMARDs, and

  • were administered BARI 4 mg (n=881) or placebo (n=803) on a background of csDMARD therapy.3

The objective was to assess the consistency of the BARI treatment effect across baseline demographic subgroups using a large pooled sample of patients with similar treatment history.3

Interaction p values ≤.10 were considered indicative of a possible interaction between treatment and subgroup.3

Efficacy Results

 Efficacy outcomes were evaluated across several baseline demographics including age.3

Treatment with BARI 4 mg daily was associated with a treatment benefit compared with placebo across subgroups based on age (Table 3).3

Table 3. Efficacy Outcomes by Age at Week 12 for Phase 2 and 3 Pooled Analysis3


ACR50 Response
n/group n (%)

PBO

ACR50 Response
n/group n (%)

BARI 4 mg

ACR50 Response
n/group n (%)

OR (95% CI)

DAS28-hsCRP ≤3.2
n/group n (%)

PBO

DAS28-hsCRP ≤3.2
n/group n (%)

BARI 4 mg

DAS28-hsCRP ≤3.2
n/group n (%)

OR (95% CI)

HAQ-DI Change From Baseline
LSM (SE) [N-obs]

PBO

HAQ-DI Change From Baseline
LSM (SE) [N-obs]

BARI 4 mg

HAQ-DI Change From Baseline
LSM (SE) [N-obs]

LSMD (95% CI)

Overall study population

127/881 (14.4)

330/803 (41.1)

4.1 (3.3, 5.2)a

146/881 (16.6)

352/803 (43.8)

4.2 (3.3, 5.3)a

-0.25 (0.03) [868]

-0.53 (0.03) [792]

-0.28 (-0.33, -0.23)a

Age (years)

<65

109/750 (14.5)

265/650 (40.8)

4.03 (3.11, 5.23)

122/750 (16.3)

278/650 (42.8)

4.07 (3.16, 5.25)

-0.24 (0.03) [739]

-0.53 (0.03) [641]

-0.28 (-0.34, -0.23)

65

18/131 (13.7)

65/153 (42.5)

4.59 (2.53, 8.30)

24/131 (18.3)

74/153 (48.4)

4.65 (2.61, 8.26)

-0.23 (0.06) [129]

-0.52 (0.06) [151]

-0.29 (-0.40, -0.17)

<75

126/867 (14.5)

319/779 (40.9)

NPb

145/867 (16.7)

337/779 (43.3)

NP

-0.25 (0.03) [854]

-0.54 (0.03) [769]

NP

75

1/14 (7.1)

11/24 (45.8)

NP

1/14 (7.1)

15/24 (62.5)

NP

-0.19 (0.16) [14]

-0.16 (0.12) [23]

NP

Abbreviations: ACR50 = American College of Rheumatology 50% response criteria; BARI = baricitinib; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; N-obs = number observed; NP = not provided; PBO = placebo; wt = weight.

a p<.001 for BARI 4 mg vs placebo in overall pooled population

b When logistic regression sample size requirements are not met, odds ratio and 95% CI are not provided within a subgroup

Post Hoc Subgroup Analysis of RA-BEACON: Effect of Age on Efficacy

Overview of Post Hoc Subgroup Analysis

A subgroup analysis of data from RA-BEACON assessed the efficacy of BARI 2 mg or 4 mg daily by baseline characteristics including age at weeks 12 and 24. Interaction p values ≤10 were considered indicative of a possible interaction between treatment and subgroup.4

The analysis did not assess the incidence of AEs by baseline age.4

Efficacy Results

The analysis did not find a significant consistent effect of baseline age for ACR20 or CDAI ≤10 at week 12 or 24 between BARI 4 mg and placebo or BARI 2 mg and placebo (Table 4).4

 

Table 4. Effect of Baseline Age on Efficacy of Baricitinib in RA-BEACON4

 

Age, <65 yearsa

Age, ≥65 yearsa 

Percent of patients achieving ACR20, n/N (%)

BARI 2 mg 

Week 12

67/139 (48)

18/35 (51)

Week 24 

61/139 (44)

17/35 (49)

BARI 4 mg 

Week 12

70/136 (51)

28/41 (68)

Week 24 

58/136 (43)

24/41 (59)

PBO

Week 12 

38/136 (28)

10/40 (25)

Week 24 

35/136 (26)

13/40 (30)

Percent of patients achieving CDAI ≤10, n/N (%)

BARI 2 mg

Week 12

34/139 (24)

7/35 (20)

Week 24

30/139 (22)

10/35 (29)

BARI 4 mg

Week 12

32/136 (24)

17/41 (41)

Week 24

35/136 (26)

20/41 (49)

PBO 

Week 12

16/136 (12)

3/40 (8)

Week 24 

22/136 (16)

5/40 (13)

Abbreviations: ACR20 = American College of Rheumatology 20% response criteria; BARI = baricitinib; CDAI = Clinical Disease Activity Index; PBO = placebo.

a p=.043 for interaction of age for BARI 4 mg vs placebo at 24 weeks (p≤.01 was considered significant).

Dosing Recommendations for the Elderly Subpopulation

Age of 65 years or 75 years has no effect on baricitinib exposure.5

Clinical experience in patients ≥75 years is very limited and in these patients a starting dose of 2 mg is appropriate.5

References

1. Fleischmann R, Alam J, Arora V, et al. Safety and efficacy of baricitinib in elderly patients with rheumatoid arthritis. RMD Open. 2017;3(2):1-5. http://dx.doi.org/10.1136/rmdopen-2017-000546

2. Kremer JM, Schiff M, Muram D, et al. Response to baricitinib therapy in patients with rheumatoid arthritis with inadequate response to csDMARDs as a function of baseline characteristics. RMD Open. 2018;4(1):e000581. http://dx.doi.org/10.1136/rmdopen-2017-000581

3. Dougados M, Rooney TP, Xie L, et al. Efficacy response to baricitinib based on baseline characteristics in patients who are inadequate responders to conventional DMARDs [abstract]. Arthritis Rheumatol. 2017;69(suppl 10):512. http://acrabstracts.org/abstract/efficacy-response-to-baricitinib-based-on-baseline-characteristics-in-patients-who-are-inadequate-responders-to-conventional-dmard/

4. Genovese MC, Kremer JM, Kartman C, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018;57(5):900-908. https://doi.org/10.1093/rheumatology/kex489

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

Glossary

AE = adverse event

BARI = baricitinib

BMI = body mass index

csDMARD = conventional synthetic disease-modifying antirheumatic drug

PYE = patient-years of exposure

RA = rheumatoid arthritis

SAE = serious 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 2020 M09 14


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