Olumiant ® (baricitinib) tabletter

För fullständig produktresumé för Olumiant se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Var Olumiant® (baricitinib) Effektiv vid Behandling av Sömnstörningar hos Patienter med Atopisk Dermatit?

Behandling med baricitinib 4 mg som monoterapi eller i kombination med topikala kortikosteroider visade en snabb och signifikant förbättring i sömnstörningar på grund av klåda jämfört med placebo .

SE_cFAQ_BAR437B_SLEEP_AD
SE_cFAQ_BAR437B_SLEEP_AD
en-GB

What Was the Effect of Baricitinib on Sleep Disturbance in BREEZE-AD Trials?

Efficacy analyses included the intent to treat (ITT) population and censored patients who discontinued study drug or received rescue therapy.1-4

Mean Change From Baseline in ADSS Item 2 at Weeks 1 and 16

Monotherapy Clinical Trials

Baseline Atopic Dermatitis Sleep Scale Item 2 Scores (number of awakenings due to itch) for Each Treatment Arm of the Monotherapy BREEZE-AD Trials shows a significant change from baseline in Atopic Dermatitis Sleep Scale (ADSS) Item 2 at week 16 in the

  • BARI 4 mg vs placebo group in
    • BREEZE-AD1 (-1.4 vs -0.8; p≤.01)
    • BREEZE-AD2 (-1.1 vs -0.5; p≤.001), and
  • BARI 2 mg vs placebo group in
    • BREEZE-AD2 (-1.0 vs -0.5; p≤.01), and
    • BREEZE-AD5 (-0.99 vs -0.40; p≤.05).1,2,5
Baseline Atopic Dermatitis Sleep Scale Item 2 Scores (number of awakenings due to itch) for Each Treatment Arm of the Monotherapy BREEZE-AD Trials1,2

BREEZE-AD1

BREEZE-AD2

BREEZE-AD5

PBO
N=249

BARI
1 mg

N=127

BARI
2 mg

N=123

BARI
4 mg

N=125

PBO
N=244

BARI
1 mg

N=125

BARI
2 mg

N=123

BARI
4 mg

N=123

PBO
N=147

BARI
1 mg

N=147

BARI
2 mg

N=146

ADSS item 2a,
mean (SD)

3.4
(5.2)

2.5
(3.4)

2.3
(4.1)

3.3
(5.2)

1.8
(2.1)

1.6
(1.8)

2.1
(2.9)

1.9
(2.5)

2.0
(2.0)

2.3
(3.3)

2.8
(3.2)

Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BARI = baricitinib; PBO = placebo.

aThe ADSS item 2 assesses the frequency of night-time awakenings due to itch the previous night on a scale of 0 to 29.

A significant change in ADSS Item 2 was achieved by week 1 with baricitinib (BARI) 4-mg treatment in BREEZE-AD1 and BREEZE-AD2, and also by week 1 with BARI 2 mg in BREEZE-AD2 and BREEZE-AD5, all continuing through week 16 (Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD1 and BREEZE-AD2 and Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD5).1,2

Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD1 and BREEZE-AD21

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; LSM = least squares mean; MMRM = mixed model for repeated measures.
* p≤.05, ** p≤.01, and *** p≤.001 for BARI vs placebo (LSM from MMRM analysis).
Note: Only the weeks 1 and 16 BARI 4 mg p values in BREEZE-AD1 and BREEZE-AD2, and weeks 1 and 16 BARI 2 mg p values in BREEZE-AD2 are controlled for multiplicity. Other p values are unadjusted.

Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD52,6

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; LS = least squares; MMRM = mixed model for repeated measures.
* p≤.05, ** p≤.01, and *** p≤.001 for BARI vs placebo (MMRM analysis).

Note: Only the weeks 1 and 16 BARI 2 mg p values are controlled for multiplicity. Other p values are unadjusted.

Combination With Topical Corticosteroid Clinical Trials

Baseline Atopic Dermatitis Sleep Scale Item 2 Scores (number of awakenings due to itch)  for Each Treatment Arm of the Combination With Topical Corticosteroid Trials BREEZE-AD4 and BREEZE-AD7  shows a significant change from baseline in ADSS Item 2 at week 16 in the BARI 4 mg + topical corticosteroids (TCS) vs placebo + TCS group in BREEZE-AD4 (-1.4 vs -0.6; p≤.001).4,5

Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD4 shows a significant change in ADSS Item 2 achieved by week 1 with BARI 4 mg + TCS treatment and continued through week 16 in BREEZE-AD4.4,5

Baseline Atopic Dermatitis Sleep Scale Item 2 Scores (number of awakenings due to itch)  for Each Treatment Arm of the Combination With Topical Corticosteroid Trials BREEZE-AD4 and BREEZE-AD73,4 

BREEZE-AD4

BREEZE-AD7

PBO + TCS
N=93

BARI 1 mg + TCS
N=93

BARI 2 mg + TCS
N=185

BARI 4 mg + TCS
N=92

PBO + TCS
N=109

BARI 2 mg + TCS 
N=109

BARI 4 mg + TCS
N=111

ADSS item 2a, mean (SD)

1.6 (1.6)

2.2 (2.7)

1.9 (3.1)

2.1 (1.8)

1.8 (2.0)

1.9 (2.3)

1.8 (2.3)

 Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BARI = baricitinib; PBO = placebo; TCS = topical corticosteroids.

aThe ADSS item 2 assesses the frequency of night-time awakenings due to itch the previous night on a scale of 0 to 29.

Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD44,7

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; LSM = least squares mean; MMRM = mixed model for repeated measures; PBO = placebo; TCS = topical corticosteroids.
* p≤.05, ** p≤.01, and *** p≤.001 for BARI vs placebo (LSM from MMRM analysis).
Note: Only the week 16 BARI 4 mg p value is controlled for multiplicity. Other p values are unadjusted.

No significant change in ADSS Item 2 was achieved at week 16 in BREEZE-AD7. However, as presented in Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD7, treatment with BARI 4 mg + TCS and BARI 2 mg + TCS did result in improvements compared with placebo + TCS at week 16 (unadjusted p≤.01).3,8

Change From Baseline in Atopic Dermatitis Sleep Scale Item 2 Through Week 16 in BREEZE-AD73,8

Abbreviations: AD = atopic dermatitis;  BARI = baricitinib; LS = least squares; MMRM = mixed model for repeated measures; PBO = placebo; TCS = topical corticosteroid.
** p≤.01 for BARI vs PBO (MMRM analysis).
Note: All p values are unadjusted.

Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment

Monotherapy Clinical Trials

As presented in Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in Monotherapy Studies BREEZE-AD1 and BREEZE-AD2, a significant percent change from baseline in ADSS Item 2 was achieved in the BARI 4 mg vs placebo group starting at day 2 (1 day after first dose) and continuing through day 7 in both BREEZE-AD1 and BREEZE-AD2 (unadjusted p≤.01).9

Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in Monotherapy Studies BREEZE-AD1 and BREEZE-AD29

Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BARI = baricitinib; LSM = least squares mean; MMRM = mixed model for repeated measures; N = range number of patients assessed at each time point per treatment arm.

* p≤.05; ** p≤.01; *** p≤.001 vs placebo (MMRM analysis, p values are not controlled for multiplicity).

In BREEZE-AD5 (Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in the Monotherapy Study BREEZE-AD5), a significant percent change from baseline in ADSS Item 2 was achieved in the BARI 2 mg vs placebo group starting at day 2 and continuing through day 7 (p≤.05), except on day 3 (Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in the Monotherapy Study BREEZE-AD5).10

Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in the Monotherapy Study BREEZE-AD510

Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BARI = baricitinib; LSM = least squares mean; MMRM = mixed model for repeated measures; PBO = placebo.

* p≤.05; ** p≤.01; *** p≤.001 vs PBO (MMRM analysis, p values are not adjusted for multiplicity).

Combination With Topical Corticosteroid Clinical Trials

Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in BREEZE-AD4 and BREEZE-AD7 presents a significant percent change from baseline in ADSS item 2 achieved in the BARI 4 mg vs placebo group

  • on day 2 and starting at day 5 and continuing through day 7 in BREEZE-AD4, and
  • starting at day 2 and continuing through day 7 in BREEZE-AD7.9,11
Daily Percent Change From Baseline in ADSS Item 2 During the First Week of Treatment in BREEZE-AD4 and BREEZE-AD79,11

Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BARI = baricitinib; LSM = least squares mean; MMRM = mixed model for repeated measures; PBO = placebo; TCS=topical corticosteroid.

* p≤.05; ** p≤.01; *** p≤.001 for BARI vs PBO (MMRM analysis, p values are not adjusted for multiplicity).

References

1Simpson EL, Lacour JP, Spelman L, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183(2):242-255. http://dx.doi.org/10.1111/bjd.18898

2Simpson EL, Forman S, Silverberg JI, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis: results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). J Am Acad Dermatol. 2021;85(1):62-70. https://doi.org/10.1016/j.jaad.2021.02.028

3Reich K, Kabashima K, Peris K, et al. Efficacy and safety of baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(12):1333-1343. https://doi.org/10.1001/jamadermatol.2020.3260

4Bieber T, Reich K, Paul C, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis who failed, are intolerant to, or have contraindication to cyclosporine: results from a randomized, placebo-controlled, phase 3 clinical trial (BREEZE-AD4). Poster presented at: 29th European Academy of Dermatology and Venereology (EADV Virtual); October 29-31, 2020.

5Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6Simpson E, Forman S, Silverberg J, et al. Efficacy and safety of baricitinib in moderate-to-severe atopic dermatitis: results from a randomized, double-blinded, placebo-controlled phase 3 clinical trial (BREEZE-AD5). Abstract presented at: Revolutionizing Atopic Dermatitis (RAD Virtual) Symposium; April 5, 2020. Accessed April 5, 2020. https://revolutionizingad.com/images/resources/2020Virtual/Abstracts/130_Simpson_RAD_Abstract_Submitted_02March2020.pdf

7Data on file, Eli Lilly and Company and/or one of its subsidiaries.

8Reich K, Kabashima K, Peris K, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in moderate to severe atopic dermatitis: results of a phase 3 randomized, double-blind, placebo-controlled 16-week trial (BREEZE-AD7). Abstract presented at: European Academy of Dermatology and Venereology 28th Congress; October 9-13, 2019; Madrid, Spain. Accessed May 24, 2021. https://eadvhighlights2019.com/articles/breeze-ad7/read

9Buhl T, Rosmarin D, Serra-Baldrich E, et al. Itch and sleep improvements with baricitinib in patients with atopic dermatitis: a post hoc analysis of 3 phase 3 studies. Dermatol Ther (Heidelb). 2021;11(3):971-982. https://doi.org/10.1007/s13555-021-00534-8

10Rosmarin D, Casillas M, Chen S, et al. Onset of symptom relief reported in daily diaries in patients with atopic dermatitis treated with baricitinib in a US clinical trial. Poster presented at: Fall Clinical Dermatology Virtual Conference; October 29-November 1, 2020.

11Buhl T, Rosmarin D, Serra E, et al. Rapid reduction of symptoms reported in daily diaries in patients with atopic dermatitis treated with baricitinib plus topical corticosteroids: results from 2 phase 3 trials. Poster presented at: 29th European Academy of Dermatology and Venereology (EADV Virtual); October 29-31, 2020. Accessed June 4, 2021. https://www.medfyle.com/articles/p-rapid-reduction-of-symptoms-reported-in-daily-diaries-with-atopic-dermatitis-treated-with-baricitinib-plus-topical-corticosteroids/download_file?filename=articles%2Farticles_content%2FP0231.pdf

Appendix

Baricitinib BREEZE-AD Clinical Program 

The effects of BARI on sleep disturbance has been evaluated using the ADSS in the following placebo-controlled trials in adult patients with moderate-to-severe AD

  • BREEZE-AD1 (N=624) and BREEZE-AD2 (N=615) compared BARI 1 mg, 2 mg, or 4 mg monotherapy to placebo in adult patients with inadequate response to TCS.1
  • BREEZE-AD4 (N=463) compared BARI 1 mg, 2 mg, or 4 mg in combination with TCS vs placebo with TCS in adult patients who were inadequate responders to, intolerant of, or contraindicated for cyclosporine.4
  • BREEZE-AD5 (N=440) compared BARI 1 mg or 2 mg monotherapy to placebo in adult patients with inadequate response to TCS.2
  • BREEZE-AD7 (N=329) compared BARI 2 mg or 4 mg in combination with TCS vs placebo with TCS in adult patients with inadequate response to topical medications.3

Note: BARI 1 mg was studied in pivotal trials, however it is not approved. Please refer to section 4.2 of the Olumiant Summary of Product Characteristics for approved dosage.

How Was Sleep Disturbance Assessed in the BREEZE-AD Clinical Program? 

During the trials, patients were allowed rescue with topical or systemic treatment at the investigator's discretion.1-3,5

Patients receiving chronic treatments to improve sleep should have been on a stable dose for at least 2 weeks prior to screening.3,5 

Sedating antihistamines including, but not limited to, alimemazine, chlorphenamine, clemastine, cyproheptadine, diphenhydramine, hydroxyzine, ketotifen, and promethazine were not permitted. Patients were allowed to use newer, less sedating antihistamines (eg, fexofenadine, loratadine, cetirizine).3,5  

Atopic Dermatitis Sleep Scale

The ADSS is a 3-item, patient-administered questionnaire.5 Lilly developed and validated the ADSS to include an assessment of the impact of itch on sleep, including

  • difficulty falling asleep (Item 1)
  • frequency of nighttime awakenings (Item 2), and
  • difficulty getting back to sleep (Item 3).5

Patients rated items 1 and 3 using a 5-point Likert-type scale with response options ranging from 0 “not at all” to 4 “very difficult.” Patients reported item 2 by selecting the number of times (ranging from of 0 to 29) they woke up each night due to itch.5 ADSS Item 3 was only answered when patients have rated item 2 more than 0.5

The ADSS was completed each day, with respondents reporting on their sleep “last night.” Each item was scored individually. Weekly mean scores using the prior 7 days were determined as long as data from at least 4 of the 7 prior days was provided. Patients completed this assessment at home via electronic daily diaries.5

Use of Atopic Dermatitis Sleep Scale in the BREEZE-AD Clinical Program 

In the BREEZE-AD trials, a key secondary endpoint was the mean change from baseline in ADSS Item 2 (frequency of nighttime awakenings due to itch) at week 1 and week 16.1-3,5

Post hoc analyses evaluated the onset of BARI effect on sleep using the daily percent change from baseline in ADSS Item 2 during the first week of treatment.9-11

Statistical Analyses

In the BREEZE-AD placebo-controlled trials, the primary and key secondary endpoints were analyzed based on a prespecified graphical testing procedure to control multiplicity. An overall family-wise type I error rate was applied and a two-sided α of 0.05 was used to test for statistical significance.1-3,5

For other endpoints, multiplicity-adjusted analyses were not conducted and unadjusted p values were shown.1-3,7

Datum fӧr senaste ӧversyn May 28, 2021


Kontakta Medicinsk Information på Lilly

Kontakta oss på telefon

Kontorstid vardagar 9.00-17.00

Eller så kan du

Klicka för att chatta är tillgänglig

Klicka för att chatta är offline

Skriv din fråga till oss