Takaisin

Baricitinib vs. placebo in patients with moderate or severe atopic dermatitis

Näytönastekatsaukset
Jorma Komulainen and Raija Sipilä
30.5.2023

Level of evidence: B

Baricitinib (2-4 mg/day) treatment alone or in combination with topical treatment appears to increase the proportion of adult patients with moderate-to-severe atopic dermatitis achieving EASI-75 response at week 16, when compared to placebo (2 mg: 18-43%, 4 mg: 21-48%, and placebo 6-23%).

In addition, baricitinib compared to placebo may increase the proportion of patients achieving EASI-90, with improvement in peak score on numerical rating scale (NRS) for pruritus.

The efficacy evidence is based on 3 RCTs with low risk of bias, applicability of the evidence is high.

Table 1. Description of the included studies
Reference Study type Population Intervention and comparison Outcomes Risk of bias
RCT=randomized controlled trial; vIGA-AD=validated Investigator's Global Assessment for Atopic Dermatitis, EASI=Eczema Area and Severity Index, NRS=Numeric Rating Scale, SCORAD= SCORing Atopic Dermatitis, DLQI=Dermatology Life Quality Index, AE=Adverse Event.
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 2 RCTs Patients ≥ 18 years of age with moderate to severe atopic dermatitis (EASI ≥ 16 and an IGA score of ≥ 3), an inadequate response to topical treatments or failure
to respond to systemic treatment.
n1=624
n2=595
Baricitinib 1, 2 or 4 mg vs. placebo Primary: vIGA-AD 0/1
Secondary: EASI-75, EASI-90, SCORAD-75, NRS, ADSS, AE
Low
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2, «Wollenberg A, Nakahara T, Maari C ym. Impact of ba...»3 RCT Patients ≥ 18 years of age with moderate to severe atopic dermatitis (EASI ≥ 16 and an IGA score of ≥ 3) and inadequate response to topical medications.
N=329
Baricitinib 4 mg + topical treatment, Baricitinib 2 mg + topical treatment, placebo + topical treatment Primary: vIGA-AD score
Secondary: EASI75 and EASI90,
SCORAD75, DLQI, safety
Low
Table 2. Additional comments for included studies
Reference Comments
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 The studies were sponsored by pharma.
Patients were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib
1 mg, 2 mg, or 4 mg.
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2 All patients received moderate- and/or lowpotency topical corticosteroids (TCS) for active lesions. Topical calcineurin inhibitors and/or crisaborole, in countries where approved, could be used in place of TCSs, with guidance to limit the use to areas considered inadvisable for TCSs.
The study was sponsored by pharma.
«Wollenberg A, Nakahara T, Maari C ym. Impact of ba...»3 All patients received moderate- and/or lowpotency topical corticosteroids (TCS) for active lesions. Topical calcineurin inhibitors and/or crisaborole, in countries where approved, could be used in place of TCSs, with guidance to limit the use to areas considered inadvisable for TCSs.
The study was sponsored by pharma.

Results

Results are shown for baricitinib 2 and 4 mg.

Table 3. Outcome 1: EASI-75 (number and proportion of patients achieving EASI-75)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C Odds ratio (95% CI)
I=intervention; C=comparison; CI=confidence interval, BARI=baricitinib; TCS=topical corticosteroid
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 RCT 1, BARI 2 mg, no concomitant TCS allowed
(123 /249)
16 23 (18.7) 22 (8.8) 2.5 (1.3-4.7)
RCT 1, BARI 4 mg, no concomitant TCS allowed
(125 /249)
16 31 (24.8) 22 (8.8) 3.7 (2.0-6.9)
RCT 2, BARI 2 mg, no concomitant TCS allowed
(123/244)
16 22 (17.9) 15 (6.1) 3.5 (1.7-7.0)
RCT 2, BARI 4 mg, no concomitant TCS allowed
(123/244)
16 26 (21.1) 15 (6.1) 4.4 (2.2-8.8)
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2 BARI 2 mg, concomitant TCS allowed
(109 / 109)
16 47 (43) 25 (23) 2.6 (1.4-4.8)
BARI 4 mg, concomitant TCS allowed
(111/109)
16 53 (48) 25 (23) 3.3 (1.8-6.0)
Level of evidence: Moderate
The quality of evidence is downgraded due to imprecision (wide confidence intervals and possible lack of clinically meaningful difference). EASI-75 was a secondary outcome.
Table 4. Outcome 2: EASI-90 (number and proportion of patients achieving EASI-90)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C Odds ratio (95% CI)
I=intervention; C=comparison; CI=confidence interval, BARI=baricitinib; TCS=topical corticosteroid; OR: odds ratio
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 RCT 1, BARI 2 mg, no concomitant TCS allowed
(123 /249)
16 13 (10.6) 12 (4.8) 2.5 (1.1-5.7)
RCT 1, BARI 4 mg, no concomitant TCS allowed
(125 /249)
16 20 (16.0) 12 (4.8) 4.1 (1.9-8.9)
RCT 2, BARI 2 mg, no concomitant TCS allowed
(123/244)
16 11 (8.9) 6 (2.5) 3.9 (1.4-10.4)
RCT 2, BARI 4 mg, no concomitant TCS allowed
(123/244)
16 16 (13.0) 6 (2.5) 6.2 (2.4-15.9)
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2 BARI 2 mg, concomitant TCS allowed
(109 / 109)
16 18 (17) 15 (14) 1.2 (0.6-2.6)
BARI 4 mg, concomitant TCS allowed
(111/109)
16 20 (18) 15 (14) 2.1 (1.0-4.2)
Level of evidence: Low
The quality of evidence is downgraded due to Inconsistency and imprecision.
Table 5. Outcome 3: IGA (Investigator's Global Assessment (IGA) score achieved 0/1)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C Odds ratio (95% CI)
I=intervention; C=comparison; CI=confidence interval, BARI=baricitinib; TCS=topical corticosteroid
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 RCT 1, BARI 2 mg, no concomitant TCS allowed
(123 /249)
16 14 (11.4) 12 (4.8) 2.6 (1.2-5.8)
RCT 1, BARI 4 mg, no concomitant TCS allowed
(125 /249)
16 21 (16.8) 12 (4.8) 4.1 (1.9-8.7)
RCT 2, BARI 2 mg, no concomitant TCS allowed
(123/244)
16 13 (10.6) 11 (4.5) 2.6 (1.1-5.9)
RCT 2, BARI 4 mg, no concomitant TCS allowed
(123/244)
16 17 (13.8) 11 (4.5) 3.6 (1.6-8.1)
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2 BARI 2 mg, concomitant TCS allowed
(109 / 109)
16 26 (24) 16 (15) 1.9 (0.9-3.9)
BARI 4 mg, concomitant TCS allowed
(111/109)
16 34 (31) 16 (15) 2.8 (1.4-5.6)
Level of evidence: Low
The quality of evidence is downgraded due to Inconsistency and imprecision.
Table 6. Outcome 4: Pruritus (Improvement in weekly average of worst daily pruritus NRS ≥ 4 points from baseline)
Reference Number of studies and number of patients (I/C) Follow-up time (weeks) Absolute number of events (%) I Absolute number of events (%) C Odds ratio (95% CI)
«Simpson EL, Lacour JP, Spelman L ym. Baricitinib i...»1 RCT 1, BARI 2 mg, no concomitant TCS allowed
(123 /249)
16 12 (12) 16 (7.2) 1.7 (0.8-3.8)
RCT 1, BARI 4 mg, no concomitant TCS allowed
(125 /249)
16 23 (21.5) 16 (7.2) 3.6 (1.8-7.2)
RCT 2, BARI 2 mg, no concomitant TCS allowed
(123/244)
16 16 (15.1) 10 (4.7) 3.6 (1.6-8.3)
RCT 2, BARI 4 mg, no concomitant TCS allowed
(123/244)
16 20 (18.7) 10 (4.7) 4.9 (2.2-10.9)
«Reich K, Kabashima K, Peris K ym. Efficacy and Saf...»2 BARI 2 mg, concomitant TCS allowed
(97 / 104)
16 37 (38) 21 (20) 2.9 (1.5-5.6)
BARI 4 mg, concomitant TCS allowed
(111/109)
16 44 (44) 21 (20) 3.8 (2.0-7.5)
Level of evidence: Low
The quality of evidence is downgraded due to Inconsistency and imprecision.

References

  1. Simpson EL, Lacour JP, Spelman L ym. 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;183:242-255 «PMID: 31995838»PubMed
  2. Reich K, Kabashima K, Peris K ym. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 2020;156:1333-1343 «PMID: 33001140»PubMed.
  3. Wollenberg A, Nakahara T, Maari C ym. Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. J Eur Acad Dermatol Venereol 2021;35:1543-1552 «PMID: 33834521»PubMed