Baricitinib vs. placebo in patients with moderate or severe atopic dermatitis
Näytönastekatsaukset
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.
| 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 in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»2, «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-sever»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 |
| Reference | Comments |
|---|---|
| «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»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»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 baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-sever»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.
| 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 in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»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. | |||||
| 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 in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»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. | |||||
| 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 in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»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. | |||||
| 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 in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase»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 Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Derm»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
- 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
- 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.
- 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