Why carry out this study?
|
The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. Network meta-analysis is a useful tool for clinicians, payers, and healthcare providers to inform decision-making about various therapies when treating patients with moderate to severe AD. |
The study analyzed 11 clinical trials for IGA 0/1, EASI-75, EASI-90, and Pruritus NRS (≥ 4-point improvement) at the primary endpoint (week 12 or 16) and at earlier timepoints. |
What was learned from the study?
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The study found that upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies across 12–16 weeks of therapy. |
This NMA suggests that some targeted systemic treatment options provide greater efficacy across key disease domains, such as skin and itch responses. These findings can help healthcare providers evaluate the overall efficacy benefit of these treatments when personalizing a patient’s treatment plan. Additionally, other factors, including safety, benefit–risk, and patient preferences, should be taken into account when personalizing a patient’s treatment plan. |
Introduction
Methods
Data Source
Selection Criteria
Outcomes
Feasibility Assessment
Statistical Analysis
Results
Systematic Literature Review
Study | Treatment | N | Age, years (mean ± SD) | Disease duration, years (mean ± SD) | Male (N, %) | Baseline EASI score (mean ± SD) | Baseline IGA score of 4 (N, %) | Baseline NRS score (mean ± SD) | Response rate observed in study at primary endpoint, % | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
EASI-75 (%) | EASI-90 (%) | IGA 0/1 (%) | ΔNRS ≥4 (%) | |||||||||
JADE MONO-1 | Abrocitinib 200 mg | 154 | 33.0 ± 17.4 | 22.7 ± 14.5 | 81 (53.0%) | 30.6 ± 14.1 | 63 (40.9%) | 7.1 ± 1.9 | 62.7 | 38.6 | 43.8 | 57.1 |
Abrocitinib 100 mg | 156 | 32.6 ± 15.4 | 24.9 ± 16.1 | 90 (58.0%) | 31.3 ± 13.6 | 64 (41.0%) | 6.9 ± 2.0 | 39.7 | 18.6 | 23.7 | 37.4 | |
Placebo | 77 | 31.5 ± 14.4 | 22.5 ± 14.4 | 49 (64.0%) | 28.7 ± 12.5 | 31 (40.3%) | 7.0 ± 1.8 | 11.8 | 5.3 | 7.9 | 14.9 | |
JADE MONO-2 | Abrocitinib 200 mg | 155 | 33.5 ± 14.7 | 20.5 ± 14.8 | 88 (56.8%) | 29.0 ± 12.4 | 49 (31.6%) | 7.0 ± 1.6 | 61.0 | 37.7 | 38.1 | 55.3 |
Abrocitinib 100 mg | 158 | 37.4 ± 15.8 | 21.1 ± 14.8 | 94 (59.5%) | 28.4 ± 11.2 | 51 (32.3%) | 7.1 ± 1.6 | 44.5 | 23.9 | 28.4 | 45.2 | |
Placebo | 78 | 33.4 ± 13.8 | 21.7 ± 14.3 | 47 (60.3%) | 28.0 ± 10.2 | 26 (33.3%) | 6.7 ± 1.9 | 10.4 | 3.9 | 9.1 | 11.5 | |
BREEZE-AD1 | Baricitinib 4 mg | 125 | 37.0 ± 12.9 | 25.0 ± 14.9 | 83 (66.4%) | 32.0 ± 12.7 | 51 (40.8%) | 6.5 ± 2.0 | 24.8 | 16.0 | 16.8 | 21.5 |
Baricitinib 2 mg | 123 | 35.0 ± 13.7 | 25.0 ± 14.6 | 82 (66.7%) | 31.0 ± 11.7 | 52 (42.3%) | 6.4 ± 2.2 | 18.7 | 10.6 | 11.4 | 12.0 | |
Placebo | 249 | 35.0 ± 12.6 | 26.0 ± 15.5 | 148 (59.4%) | 32.0 ± 13.0 | 105 (42.2%) | 6.7 ± 2.0 | 8.8 | 4.8 | 4.8 | 7.2 | |
BREEZE-AD2 | Baricitinib 4 mg | 123 | 34.0 ± 14.1 | 23.0 ± 14.8 | 82 (66.7%) | 33.0 ± 12.7 | 63 (51.2%) | 6.6 ± 2.2 | 21.1 | 13.0 | 13.8 | 18.7 |
Baricitinib 2 mg | 123 | 36.0 ± 13.2 | 24.0 ± 13.8 | 65 (52.9%) | 35.0 ± 16.0 | 62 (50.4%) | 6.6 ± 2.2 | 17.9 | 8.9 | 10.6 | 15.1 | |
Placebo | 244 | 35.0 ± 13.0 | 25.0 ± 13.9 | 154 (63.1%) | 33.0 ± 12.8 | 121 (49.6%) | 6.8 ± 2.2 | 6.1 | 2.5 | 4.5 | 4.1 | |
BREEZE-AD5 | Baricitinib 2 mg | 146 | 40.0 ± 15.0 | 24.0 ± 16.0 | 69 (47.3%) | 26.6 ± 11.0 | 61 (41.8%) | 7.3 ± 2.1 | 29.5 | 20.5 | 24.0 | 25.2 |
Placebo | 147 | 39.0 ± 17.0 | 23.0 ± 17.0 | 80 (54.4%) | 27.0 ± 11.0 | 61 (41.5%) | 7.0 ± 2.4 | 8.2 | 3.4 | 5.4 | 5.7 | |
SOLO 1 | Dupilumab 300 mg | 224 | 39.8 ± 14.7 | 28.5 ± 16.1 | 130 (58.0%) | 33.0 ± 13.6 | 108 (48.2%) | 7.2 ± 1.9 | 51.3 | 35.7 | 37.9 | 40.8 |
Placebo | 224 | 39.5 ± 13.9 | 29.5 ± 14.5 | 118 (52.7%) | 34.5 ± 14.5 | 110 (49.1%) | 7.4 ± 1.8 | 14.7 | 7.6 | 10.3 | 12.3 | |
SOLO 2 | Dupilumab 300 mg | 233 | 36.9 ± 14.0 | 27.2 ± 14.2 | 137 (58.8%) | 31.8 ± 13.1 | 115 (49.4%) | 7.6 ± 1.6 | 44.2 | 30.0 | 36.1 | 36.0 |
Placebo | 236 | 37.4 ± 14.1 | 28.2 ± 14.4 | 132 (55.9%) | 33.6 ± 14.3 | 115 (48.7%) | 7.5 ± 1.9 | 11.9 | 7.2 | 8.5 | 9.5 | |
ECZTRA 1 | Tralokinumab 300 mg | 603 | 38.6 ± 13.7 | 27.9 ± 14.5 | 351 (58.2%) | 32.2 ± 13.7 | 305 (50.6%) | 7.7 ± 1.4 | 25.0 | 14.5 | 15.8 | 20.0 |
Placebo | 199 | 39.4 ± 15.2 | 29.6 ± 15.1 | 123 (61.8%) | 32.9 ± 13.9 | 102 (51.3%) | 7.7 ± 1.4 | 12.7 | 4.1 | 7.1 | 10.3 | |
ECZTRA 2 | Tralokinumab 300 mg | 593 | 37.2 ± 14.7 | 28.3 ± 15.9 | 359 (60.5%) | 32.1 ± 14.3 | 286 (48.2%) | 7.9 ± 1.5 | 33.2 | 18.3 | 22.2 | 25.0 |
Placebo | 201 | 35.1 ± 14.0 | 27.5 ± 14.7 | 114 (56.7%) | 32.6 ± 13.9 | 101 (50.3%) | 8.0 ± 1.4 | 11.4 | 5.5 | 10.9 | 9.5 | |
Measure Up 1 | Upadacitinib 30 mg | 285 | 33.6 ± 15.8 | 20.4 ± 14.3 | 155 (54.4%) | 29.0 ± 11.1 | 125 (43.9%) | 7.3 ± 1.5 | 79.7 | 65.8 | 62.0 | 60.0 |
Upadacitinib 15 mg | 281 | 34.1 ± 15.7 | 20.5 ± 15.9 | 157 (55.9%) | 30.6 ± 12.8 | 127 (45.2%) | 7.2 ± 1.6 | 69.6 | 53.1 | 48.1 | 52.2 | |
Placebo | 281 | 34.4 ± 15.5 | 21.3 ± 15.3 | 144 (51.3%) | 28.8 ± 12.6 | 131 (46.6%) | 7.3 ± 1.7 | 16.3 | 8.1 | 8.4 | 11.8 | |
Measure Up 2 | Upadacitinib 30 mg | 282 | 34.1 ± 16.0 | 20.8 ± 14.3 | 162 (57.5%) | 29.7 ± 12.2 | 156 (55.3%) | 7.3 ± 1.6 | 72.9 | 58.5 | 52.0 | 59.6 |
Upadacitinib 15 mg | 276 | 33.3 ± 15.7 | 18.8 ± 13.3 | 155 (56.2%) | 28.6 ± 11.7 | 150 (54.4%) | 7.2 ± 1.6 | 60.1 | 42.4 | 38.8 | 41.9 | |
Placebo | 278 | 33.4 ± 14.8 | 21.1 ± 13.6 | 154 (55.4%) | 29.1 ± 12.1 | 153 (55.0%) | 7.3 ± 1.6 | 13.3 | 5.4 | 4.7 | 9.1 |
Network Meta-Analysis
Outcome | Treatment | Na | Odds ratio versus placebo | NNT | Response rate | SUCRA (%) | ||
---|---|---|---|---|---|---|---|---|
Primary endpoint timepoint | ||||||||
EASI-75 | Abrocitinib 100 mg | 314 | 5.93 (3.49–10.72) | 3.2 (2.1–5.9) | 43.0% (24.8–64.0%) | 53.9 | ||
Abrocitinib 200 mg | 309 | 13.27 (7.80–24.05) | 2.0 (1.6–2.9) | 62.9% (42.5–79.9%) | 85.8 | |||
Baricitinib 2 mg | 392 | 3.31 (2.27–4.87) | 5.5 (3.4–10.6) | 29.6% (16.8–46.8%) | 23.2 | |||
Baricitinib 4 mg | 248 | 4.07 (2.64–6.31) | 4.4 (2.8–8.4) | 34.1% (19.4–52.6%) | 36.4 | |||
Dupilumab 300 mg | 457 | 6.05 (4.38–8.44) | 3.1 (2.3–4.9) | 43.5% (27.4–61.0%) | 55.6 | |||
Tralokinumab 300 mg | 1196 | 3.02 (2.19–4.24) | 6.1 (3.8–11.4) | 27.8% (15.9–43.9%) | 19.1 | |||
Upadacitinib 15 mg | 557 | 10.89 (8.16–14.71) | 2.1 (1.8–2.9) | 58.1% (40.9–73.5%) | 77.9 | |||
Upadacitinib 30 mg | 567 | 19.08 (14.14–26.02) | 1.7 (1.5–2.1) | 70.8% (54.7–83.0%) | 98.3 | |||
Placebo | 2214 | 11.3% (6.3–19.2%) | 0.0 | |||||
EASI-90 | Abrocitinib 100 mg | 314 | 5.98 (2.84–14.92) | 5.1 (2.3–14.2) | 24.9% (10.7–50.6%) | 46.3 | ||
Abrocitinib 200 mg | 309 | 13.49 (6.51–33.31) | 2.7 (1.6–5.6) | 42.8% (21.4–69.7%) | 82.5 | |||
Baricitinib 2 mg | 392 | 3.98 (2.40–6.79) | 7.9 (3.9–19.0) | 18.0% (8.6–34.3%) | 23.8 | |||
Baricitinib 4 mg | 248 | 5.50 (3.11–9.94) | 5.6 (2.9–13.0) | 23.2% (11.1–42.8%) | 44.0 | |||
Dupilumab 300 mg | 457 | 6.20 (4.19–9.41) | 5.0 (2.9–9.6) | 25.5% (13.4–43.2%) | 50.2 | |||
Tralokinumab 300 mg | 1196 | 3.99 (2.51–6.73) | 7.9 (3.9–18.2) | 18.1% (8.7–34.2%) | 25.0 | |||
Upadacitinib 15 mg | 557 | 12.84 (8.93–18.85) | 2.8 (1.9–4.6) | 41.4% (24.5–60.8%) | 79.8 | |||
Upadacitinib 30 mg | 567 | 23.17 (16.07–34.06) | 2.0 (1.5–2.9) | 56.1% (37.0–73.6%) | 98.4 | |||
Placebo | 2214 | 5.2% (2.7–9.9%) | 0.0 | |||||
IGA 0/1 | Abrocitinib 100 mg | 314 | 3.88 (2.14–7.58) | 6.4 (3.1–17.0) | 22.9% (10.7–43.3%) | 38.6 | ||
Abrocitinib 200 mg | 309 | 7.71 (4.30–14.95) | 3.4 (2.0–6.8) | 37.2% (19.4–60.1%) | 73.3 | |||
Baricitinib 2 mg | 392 | 3.39 (2.16–5.41) | 7.5 (3.9–17.3) | 20.6% (10.3–36.9%) | 30.6 | |||
Baricitinib 4 mg | 248 | 4.38 (2.58–7.47) | 5.6 (3.0–12.8) | 25.0% (12.4–44.0%) | 46.3 | |||
Dupilumab 300 mg | 457 | 5.75 (4.01–8.39) | 4.3 (2.7–7.8) | 30.5% (17.0–48.7%) | 60.3 | |||
Tralokinumab 300 mg | 1196 | 2.39 (1.67–3.52) | 12.1 (6.0–29.1) | 15.5% (7.8–28.3%) | 15.7 | |||
Upadacitinib 15 mg | 557 | 11.12 (7.77–16.40) | 2.6 (1.9–4.1) | 46.0% (28.3–64.8%) | 85.3 | |||
Upadacitinib 30 mg | 567 | 19.47 (13.57–28.75) | 1.9 (1.5–2.7) | 59.8% (40.9–76.3%) | 99.9 | |||
Placebo | 2214 | 7.1% (3.8–13.0%) | 0.0 | |||||
ΔNRS ≥ 4 | Abrocitinib 100 mg | 314 | 4.59 (2.78–7.95) | 4.6 (2.6–10.0) | 30.5% (15.3–52.1%) | 47.0 | ||
Abrocitinib 200 mg | 309 | 8.30 (5.03–14.38) | 2.8 (1.9–5.2) | 44.3% (24.6–66.3%) | 82.3 | |||
Baricitinib 2 mg | 392 | 3.17 (2.03–5.04) | 7.0 (3.7–16.4) | 23.3% (11.4–41.7%) | 25.1 | |||
Baricitinib 4 mg | 248 | 4.49 (2.71–7.50) | 4.7 (2.7–10.3) | 30.0% (15.1–51.0%) | 47.1 | |||
Dupilumab 300 mg | 457 | 5.16 (3.63–7.44) | 4.1 (2.7–7.7) | 33.0% (18.0–52.6%) | 54.7 | |||
Tralokinumab 300 mg | 1196 | 2.64 (1.86–3.84) | 8.9 (4.7–19.8) | 20.1% (10.1–36.3%) | 17.0 | |||
Upadacitinib 15 mg | 557 | 7.56 (5.53–10.53) | 3.0 (2.2–5.0) | 41.9% (24.6–61.6%) | 77.7 | |||
Upadacitinib 30 mg | 567 | 12.88 (9.42–17.94) | 2.2 (1.7–3.2) | 55.2% (35.7–73.2%) | 98.9 | |||
Placebo | 2214 | 8.7% (4.4–16.5%) | 0.0 | |||||
Week 2b | ||||||||
EASI-75 | Abrocitinib 100 mg | 314 | 4.65 (1.76–16.36) | 10.6 (2.9–54.9) | 12.6% (3.9–38.8%) | 43.2 | ||
Abrocitinib 200 mg | 309 | 13.02 (5.13–44.86) | 3.9 (1.7–11.8) | 28.9% (10.3–63.5%) | 79.6 | |||
Baricitinib 2 mg | 392 | 4.32 (2.52–7.68) | 11.5 (4.8–32.3) | 11.8% (4.8–26.4%) | 39.4 | |||
Baricitinib 4 mg | 248 | 7.37 (4.08–13.76) | 6.5 (3.0–16.7) | 18.5% (7.6–38.7%) | 61.1 | |||
Dupilumab 300 mg | 457 | 3.54 (2.00–6.64) | 14.8 (5.6–46.8) | 9.8% (3.9–23.3%) | 33.0 | |||
Tralokinumab 300 mg | 1196 | 1.78 (0.95–3.65) | 43.5 (−250.5 to 479.2) | 5.2% (1.9–13.9%) | 14.0 | |||
Upadacitinib 15 mg | 557 | 15.18 (9.59–25.47) | 3.5 (2.0–7.2) | 31.9% (15.4–55.0%) | 81.6 | |||
Upadacitinib 30 mg | 567 | 23.20 (14.72–38.84) | 2.6 (1.7–4.9) | 41.7% (21.9–65.1%) | 97.6 | |||
Placebo | 2214 | 3.0% (1.3–6.5%) | 0.5 | |||||
ΔNRS ≥ 4 | Abrocitinib 100 mg | 314 | 18.34 (13.47–25.30) | 5.0 (1.9–23.5) | 21.6% (4.5–61.5%) | 56.9 | ||
Abrocitinib 200 mg | 309 | 44.43 (34.17–59.58) | 2.6 (1.4–9.9) | 40.0% (10.4–79.5%) | 87.8 | |||
Baricitinib 2 mg | 392 | 5.85 (3.53–9.01) | 15.5 (3.7–89.1) | 8.0% (1.4–34.4%) | 18.2 | |||
Baricitinib 4 mg | 248 | 9.15 (5.28–15.49) | 9.6 (2.6–53.1) | 12.0% (2.2–45.8%) | 39.5 | |||
Dupilumab 300 mg | 457 | 7.18 (5.12–9.79) | 12.2 (3.2–65.2) | 9.7% (1.8–38.5%) | 28.4 | |||
Tralokinumab 300 mgc | ||||||||
Upadacitinib 15 mg | 557 | 30.09 (24.72–36.90) | 3.4 (1.6–14.2) | 31.1% (7.3–72.0%) | 71.5 | |||
Upadacitinib 30 mg | 567 | 52.15 (43.52–63.29) | 2.4 (1.4–8.5) | 43.9% (12.1–81.7%) | 97.8 | |||
Placebo | 1814 | 1.5% (0.3–7.8%) | 0.0 |