Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review
Abstract
:1. Introduction
2. Material and Method
2.1. Search Strategy and Inclusion Criteria
2.2. Study Selection
2.3. Outcomes
2.4. Assessment of Risk of Bias
2.5. Data Extraction and Quality Assessment
2.6. Strategy for Data Synthesis
3. Results
3.1. Study Selection
3.2. Baseline Characteristics
3.3. Efficacy Outcomes
Publication Data | Study Design | Study Arm Baseline Characteristics | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Study ID | Year | Phase | Agent | Dosing, Schedule, Route | n | Males n (%) | Age Mean/Median | Adolescent (12–17 Years) n (%) | Race (White) n (%) | Disease Duration Years Mean/Median | Basal EASI Score Mean/Median | Basal BSA % Mean/Median | Basal SCORAD Score Mean/Median | Weekly WP-NRS Score Mean/Median | vIGA-AD Score = 4 n (%) | DLQI Score Mean/Median |
LIBERTY AD CHRONOS * [10] | 2017 | 3 | Placebo + TCS | QW sc | 315 | 193 (61.3) | 34.0 (25.0–45.0) | 0 | 208 (66.0) | 26.0 (17.0–38.0) | 29.6 (22.2–40.8) | 55.0 (40.0–75.0) | 64.1 (55.9–76.1) | 7.6 (6.3–8.6) | 147 (46.6) | 14.0 (9.0–20.0) |
Dupilumab + TCS | 300 mg Q2W sc | 106 | 62 (58.5) | 40.5 (28.0–49.0) | 0 | 74 (69.8) | 28.0 (20.0–44.0) | 30.9 (22.3–41.6) | 58.8 (43.5–78.5) | 69.7 (60.4–79.8) | 7.7 (6.6–8.5) | 53 (50.0) | 13.5 (8.0–20.0) | |||
Dupilumab + TCS | 300 mg QW sc | 319 | 191 (59.9) | 34.0 (26.0–45.0) | 0 | 208 (65.2) | 26.0 (18.0–39.0) | 29.0 (21.6–40.7) | 52.0 (36.0–71.5) | 65.3 (55.2–76.3) | 7.4 (6.0–8.6) | 147 (46.1) | 14.0 (8.0–20.0) | |||
ECZTRA-1 * [11] | 2020 | 3 | Placebo | Q2W sc | 199 | 123 (61.8) | 37.0 (26.0–49.0) | 0 | 138 (69.3) | 28.0 (18.0–41.0) | 30.3 (22.0–41.5) | 52.5 (31.0–77.0) | 70.8 (63.8–81.0) | 7.9 (6.9–8.7) | 102 (51.3) | 16.0 (13.0–22.0) |
Tralokinumab | 300 mg Q2W sc | 603 | 351 (58.2) | 37.0 (27.0–48.0) | 0 | 426 (70.6) | 27.0 (19.0–38.0) | 28.2 (21.3–40.0) | 50.0 (33.0–70.0) | 69.2 (61.5–79.1) | 7.9 (6.7–8.9) | 305 (50.6) | 17.0 (12.0–22.0) | |||
ECZTRA-2 * [11] | 2020 | 3 | Placebo | Q2W sc | 201 | 114 (56.7) | 30.0 (23.0–46.0) | 0 | 123 (61.2) | 25.0 (18.0–36.0 | 29.6 (20.6–41.4) | 50.0 (31.0–74.0) | 69.9 (61.9–79.1) | 8.1 (7.1–9.0) | 101 (50.2) | 18.0 (12.5–24.0) |
Tralokinumab | 300 mg Q2W sc | 593 | 359 (60.5) | 34.0 (25.0–48.0) | 0 | 374 (63.1) | 25.5 (17.0–39.0) | 28.2 (19.8–40.8) | 50.0 (31.0–74.0) | 69.5 (60.5–79.1) | 8.0 (7.0–9.0) | 286 (48.2) | 18.0 (13.0–23.0) | |||
BREEZE-AD3 ** [12] | 2021 | 3 | Baricitinib | 2 mg QD oral | 54 | 28 (51.9) | 32.8 (12.7) | 0 | 45 (83.3) | 19.2 (11.8) | 24.9 (8.7) | NR | 62.2 (12.0) | 6.1 (2.2) | 18 (33.3) | NR |
Baricitinib | 4 mg QD oral | 70 | 42 (60.0) | 36.7 (15.5) | 0 | 47 (67.1) | 23.2 (16.8) | 28.1 (10.6) | NR | 63.4 (12.3) | 6.5 (2.1) | 22 (31.4) | NR | |||
AD Up **, *** [13] | 2021 | 3 | Placebo | QD oral | 304 | 178 (58.6) | 34.3 (12–75) | 40 (13.2) | 225 (74.0) | 24.3 (15.2) | 30.3 (13.0) | 48.6 (23.1) | NR | 7.1 (1.6) | 163 (53.6) | 16.3 (7.0) |
Upadacitinib + TCS | 15 mg QD oral | 300 | 179 (59.7) | 32.5 (13–74) | 39 (13.0 | 204 (68.0) | 22.9 (13.9) | 29.2 (11.8) | 46.7 (21.6) | NR | 7.1 (1.8) | 157 (52.3) | 16.4 (7.2) | |||
Upadacitinib + TCS | 30 mg QD oral | 297 | 190 (64.0) | 35.5 (12–72) | 37 (12.5) | 218 (73.4) | 23.1 (16.1) | 29.7 (11.8) | 48.5 (23.1) | NR | 7.4 (1.6) | 157 (52.9) | 17.1 (7.0) | |||
Measure Up 1 **, *** [14] | 2022 | 3 | Placebo | QD oral | 281 [244] | 144 (51.2) | 34.4 (12–75) | 40 (14.2) | 182 (64.8) | 21.3 (15.3) | 28.8 (12.6) | 45.7 (21.6) | 66.1 (12.9) | 7.3 (1.7) | 122 (44.5) | 17.0 (6.8) |
Upadacitinib + TCS | 15 mg QD oral | 281 | 157 (55.9) | 34.1 (12–74) | 42 (14.9) | 182 (64.8) | 20.5 (15.9) | 30.6 (12.8) | 48.5 (22.2) | 68.2 (12.6) | 7.2 (1.6) | 127 (45.2) | 16.2 (7.0) | |||
Upadacitinib + TCS | 30 mg QD oral | 285 | 155 (54.4) | 33.6 (12–75) | 42 (14.7) | 191 (67.0) | 20.4 (14.3) | 29.0 (11.1) | 47.0 (22.0) | 67.3 (12.5) | 7.3 (1.5) | 131 (46.0) | 16.4 (7.0) | |||
Measure Up 2 **, *** [14] | 2022 | 3 | Placebo | QD oral | 278 [241] | 154 (55.4) | 33.4 (13–71) | 36 (12.9) | 195 (70.1) | 21.1 (13.6) | 29.1 (12.1) | 47.6 (22.7) | 67.9 (12.1) | 7.3 (1.6) | 153 (55.0) | 17.1 (7.2) |
Upadacitinib + TCS | 15 mg QD oral | 276 | 155 (56.2) | 33.3 (12–74) | 33 (12.0) | 184 (66.7) | 18.8 (13.3) | 28.6 (11.7) | 45.1 (22.4) | 66.6 (12.5) | 7.2 (1.6) | 150 (54.3) | 16.9 (7.0) | |||
Upadacitinib + TCS | 30 mg QD oral | 282 | 162 (57.4) | 34.1 (12–75) | 35 (12.4) | 198 (70.2) | 20.8 (14.3) | 29.7 (12.2) | 47.0 (23.2) | 66.7 (13.0) | 7.3 (1.6) | 156 (55.3) | 16.7 (6.9) |
Publication Data | Study Design | Efficacy (w52) | Safety (w52) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Study ID | Year | Phase | Agent | Dosing, Schedule, Route | n | n 16w | EASI 50 | EASI 75 | EASI 90 | EASI 100 | vIGA-AD 0/1 | Mean Reduction DLQI | WP-NRS Improvement ≥4 | At Least One AE | At Least One Serious AE | At Least One Infectious AE | Withdrawal Due to AE |
LIBERTY AD CHRONOS [10] | 2017 | 3 | Placebo + TCS | QW sc | E = 264 S = 315 | 29.9% | 21.6% | 15.5% | NR | 12.5% | −5.6 (0.36) | 12.9% (32/249) | 266 (84.4) | 16 (5.1) | 182 (57.8) | 24 (7.6) | |
Dupilumab + TCS | 300 mg Q2W sc | E = 89 S = 110 | 78.7% * | 65.2% * | 50.6% * | NR | 36.0% * | −10.9 (0.59) * | 51.2% (44/86) * | 97 (88.2) | 4 (3.6) | 63 (57.3) | 2 (1.8) | ||||
Dupilumab + TCS | 300 mg QW sc | E = 270 S = 315 | 70.0% * | 64.1% * | 50.7% * | NR | 40.0% * | −10.7 (0.36) * | 39.0% (97/249) * | 261 (82.9) | 9 (2.9) | 166 (52.7) | 9 (2.9) | ||||
ECZTRA-1 [11] | 2020 | 3 | Placebo | 199 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
Tralokinumab | 300 mg Q2W sc | 603 | Placebo n = 35 | NR | 33.3% | NR | NR | 47.4% | NR | NR | 25 (71.4) | 0 | NR | 0 | |||
Q2W n = 68 | 59.6% | 51.3% | 54 (79.4) | 1 (1.5) | 1 (1.5) | ||||||||||||
Q4W n = 76 | 49.1% | 38.9% | 53 (69.7) | 3 (3.9) | 1 (1.3) | ||||||||||||
ECZTRA-2 [11] | 2020 | 3 | Placebo | 201 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
Tralokinumab | 300 mg Q2W sc | 593 | Placebo n = 46 | NR | 21.4% | NR | NR | 25.0% | NR | NR | 32 (69.6) | 0 | NR | 0 | |||
Q2W n = 91 | 55.8% * | 59.3% * | 62 (68.1) | 0 | 2 (2.2) | ||||||||||||
Q4W n = 89 | 51.4% * | 44.9% | 56 (62.9) | 3 (3.4) | 1 (1.) | ||||||||||||
BREEZE-AD3 [12] | 2021 | 3 | Baricitinib | 2 mg QD oral | 216 | 54 | NR | 81.5% | NR | NR | 59.3% | −7.9 (7.9) | NR | NR | NR | NR | NR |
Baricitinib | 4 mg QD oral | 216 | 70 | NR | 55.7% | NR | NR | 47.1% | −7.1 (6.7) | NR | NR | NR | NR | NR | |||
AD Up [13] | 2021 | 3 | Placebo + TCS Upadacitinib + TCS | 15 mg QD oral | 144 | NR | 79.1% (71.7–86.6) | 60.8% (51.8–69.8) | 27.0% (18.9–35.1) | 56.9% (47.8–66.0) | NR | 61.3% (52.2–70.3) | 338.0 E/100 PY | 8.0 E/100 PY | NR | 20/443 (4.5) | |
Upadacitinib + TCS | 15 mg QD oral | 300 | 289 | NR | 50.8% (45.1–56.5) | 37.7% (32.1–43.3) | 13.1% (9.2–16.9) | 33.5% (28.1–38.9%) | NR | 45.3% (39.5–51.0) | |||||||
Placebo + TCS Upadacitinib + TCS | 30 mg QD oral | 139 | NR | 84.7% (77.3–92.1) | 71.8% (62.2–81.5%) | 26.3% (17.3–35.3) | 65.5% (55.7–75.2) | NR | 70.7% (61.3–80.2) | 346.6 E/100 PY | 8.1 E/100 PY | NR | 20/436 (4.6) | ||||
Upadacitinib + TCS | 30 mg QD oral | 297 | 287 | NR | 69.0% (63.7–74.3) | 55.4% (49.7–61.2) | 23.6% (18.8–28.5) | 45.2% (39.5–50.9) | NR | 57.5% (51.8–63.2) | |||||||
Measure Up 1 [14] | 2022 | 3 | Placebo + TCS Upadacitinib + TCS (w16) | 15 mg QD oral | 121 | NR | NR | NR | NR | NR | NR | NR | 262.4 E/100 PY | 6.5 E/100 PY | NR | 22 (5.5) | |
Upadacitinib + TCS | 15 mg QD oral | 281 | NR | 82.0% (77.0–86.9) | 62.7% (56.5–68.9) | 27.9% (22.1–33.7) | 59.2% (52.9–65.5) | NR | 67.3% (61.1–73.4) | ||||||||
Placebo + TCS Upadacitinib + TCS (w16) | 30 mg QD oral | 123 | NR | NR | NR | NR | NR | NR | NR | 330.9 E/100 PY | 10.0 E/100 PY | NR | 39 (9.6) | ||||
Upadacitinib + TCS | 30 mg QD oral | 285 | NR | 84.9% (80.3–89.5) | 73.3% (67.6–79.0) | 35.8% (29.6–41.9) | 62.5% (56.3–68.7) | NR | 67.7% (61.6–73.7) | ||||||||
Measure Up 2 [14] | 2022 | 3 | Placebo + TCS Upadacitinib + TCS (w16) | 15 mg QD oral | 120 | NR | NR | NR | NR | NR | NR | NR | 240.9 E/100 PY | 7.1 E/100 PY | NR | 21 (5.3) | |
Upadacitinib + TCS | 15 mg QD oral | 276 | NR | 79.1% (73.9–84.4) | 61.3% (55.0–67.6) | 27.8% (22.0–33.6) | 52.6% (46.2–59.1) | NR | 62.4% (56.1–68.7) | ||||||||
Placebo + TCS Upadacitinib + TCS (w16) | 30 mg QD oral | 121 | NR | NR | NR | NR | NR | NR | NR | 270.9 E/100 PY | 6.9 E/100 PY | NR | 31 (7.7) | ||||
Upadacitinib + TCS | 30 mg QD oral | 282 | NR | 84.3 (79.6–89.0) | 70.3% (64.4–76.2) | 35.8% (29.6–42.0) | 65.1% (58.9–71.2) | NR | 72.9% (67.1–78.7) |
3.4. Safety
4. Discussion
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Ayen-Rodríguez, A.; Pereyra-Rodríguez, J.-J.; Navarro-Triviño, F.J.; Alcantara-Luna, S.; Domínguez-Cruz, J.; Galán-Gutiérrez, M.; Vilar-Palomo, S.; Armario-Hita, J.C.; Ruiz-Villaverde, R. Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review. Life 2022, 12, 1159. https://doi.org/10.3390/life12081159
Ayen-Rodríguez A, Pereyra-Rodríguez J-J, Navarro-Triviño FJ, Alcantara-Luna S, Domínguez-Cruz J, Galán-Gutiérrez M, Vilar-Palomo S, Armario-Hita JC, Ruiz-Villaverde R. Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review. Life. 2022; 12(8):1159. https://doi.org/10.3390/life12081159
Chicago/Turabian StyleAyen-Rodríguez, Angela, José-Juan Pereyra-Rodríguez, Francisco J. Navarro-Triviño, Sara Alcantara-Luna, Javier Domínguez-Cruz, Manuel Galán-Gutiérrez, Samuel Vilar-Palomo, Jose Carlos Armario-Hita, and Ricardo Ruiz-Villaverde. 2022. "Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review" Life 12, no. 8: 1159. https://doi.org/10.3390/life12081159