Introduction
Literature Analysis
References | Study design | Patient characteristics | Treatment and duration | Frequency of application site burning, stinging, pain, discomfort | Frequency of application site pruritus | Frequency of application site paresthesia, other |
---|---|---|---|---|---|---|
Reitamo et al. [48] | Phase 3, OL, multicenter, noncomparative study | Mod-sev AD (Rajka and Langelanda criteria; 5–60% total BSA), 18–70 years, N = 316 | TAC, 0.1% BID for 6 or 12 months | Burningb—43.7% (n = 138) | Pruritusb—19.0% (n = 60) | |
Wahn et al. [32] | DB, randomized controlled study | AD (IGA score ≥ 2; ≥ 5% total BSA), 2–17 years, N = 713 | 2:1 PIM, 1% vs. VEH BID prn for 1 year; TCS for flares; emollients part of both regimens | Burningc—10.5% (PIM), 9.3% (VEH) | ||
Eichenfield et al. [24] | Two randomized, multicenter, DB, vehicle-controlled studies | Mi-mod AD (IGA score of 2 or 3; ≥ 5% total BSA), 1–17 years, N = 403 | 2:1 PIM, 1% vs. VEH BID for 6 weeks | Burningb—10.4% (PIM), 12.5% (VEH) | Local AEs—28% (PIM), 35% (VEH) | |
Meurer et al. [34] | Randomized, DB, parallel-group, multicenter study | Mod-sev AD (IGA score of 3 or 4; ≥ 5% total BSA), 18–69 years, N = 192 | 1:1 PIM, 1% vs. VEH BID as needed for 24 weeks; TCS for flares; emollients part of both regimens | Burning—10.4% (n = 10, PIM), 3.1% (n = 3, VEH) Discontinuation due to burning—1.0% (n = 1, VEH) | ||
Ho et al. [41] | DB, randomized study; followed by 20-week OL safety extension study | Mi-mod AD (IGA score of 2 or 3; ≥ 5% total BSA), 3–23 months, N = 186 | PIM, 1% or VEH BID for 6 weeks (DB); PIM, 1% for 20 weeks (OL) | Irritation—0% (PIM, DB), 4.8% (VEH, DB) Burning—0.8% (PIM, DB), 1.6% (VEH, DB) | ASR not otherwise specified—1.6% (PIM, DB), 1.6% (VEH, DB) | |
Kang et al. [42] | Three DB, randomized, vehicle-controlled, multicenter studies | Mod-sev AD (Rajka and Langelanda criteria), 16–79 years, N = 983 | VEH, TAC, 0.03% or TAC, 0.1% BID for up to 12 weeks | Burning, head/neck area—30% (TAC, 0.03%)f, 40% (TAC, 0.1%)f, 19% (VEH) Burning, non-head/neck area—38% (TAC, 0.03%)f, 42% (TAC, 0.1%)f, 23% (VEH) | Pruritus, head/neck area—32% (TAC, 0.03%), 31% (TAC, 0.1%), 29% (VEH) Pruritus, non-head/neck area—41% (TAC, 0.03%)f, 39% (TAC, 0.1%)f, 30% (VEH) | Tingling, head/neck area—32% (TAC, 0.03%), 5% (TAC, 0.1%), 2% (VEH) Tingling, non-head/neck area—3% (TAC, 0.03%), 3% (TAC, 0.1%), 2% (VEH) Discontinuation due to AS AE, head/neck area—3.4% (TAC), 8.4% (VEH) Discontinuation due to AS AE, non-head/neck area—3.5% (TAC), 8.8% (VEH) |
Lan et al. [43] | OL, single-arm, multicenter study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 10% total BSA), 4–50 years, N = 68 (adult n = 42; pediatric n = 26) | TAC, 0.03% (2–15 years and > 16 years) or 0.1% BID (> 16 years) for 4 weeks | Burningb—52.9% (TAC combined group, n = 36)d Stingingb—10.3% (TAC combined group, n = 7)d Pain—1.5% (TAC combined group, n = 1)d | Pruritusb—33.8% (TAC combined group, n = 23)d | Most common AEs generally involved local irritation (i.e., burning and stinging) |
Tan and Langley [47] | OL, noncomparative, multicenter study | Mi-sev AD (Rajka and Langelanda criteria), 2–72 years, N = 236 | TAC, 0.1% BID for up to 6 months | Burningc—38.1% (n = 90) Discontinuation due to burning—0.9% (n = 2) | Pruritusc—33.9% (n = 80) | |
Kempers et al. [57] | Multicenter, randomized, parallel-group study | Mod AD (IGA score of 3), 2–17 years, N = 141 | 1:1 PIM, 1% vs. TAC, 0.03% BID for up to 6 weeks (randomized); PIM, 1% for 20 weeks (OL) | Warmth/stinging/burning (randomized)—20% (PIM, n = 14), 17% (TAC, n = 12) | Erythema/irritation (randomized)—8% (PIM, n = 6), 19% (TAC, n = 13)f Pruritus (randomized)—8% (PIM, n = 6), 20% (TAC, n = 14) | Unspecified ASRs (randomized)—24% (PIM, n = 17), 26% (TAC, n = 18) |
Meurer et al. [33] | Randomized, DB, parallel-group, multicenter study | Mod AD (IGA score of 3; ≥ 5% total BSA), 18–66 years, N = 130 | 1:1 PIM, 1% vs. VEH prn for 24 weeks; TCS for flares; emollients part of both regimens | ASRs (burning/erythema/pain/pruritus)b—14.5% (PIM, n = 9), 8.8% (VEH, n = 6) | ||
Won et al. [46] | OL, noncomparative, multicenter study | Mod-sev AD (Rajka and Langelanda criteria; > 10% total BSA), 2–57 years N = 180 | TAC, 0.03% BID for 4 weeks | Burning—45.3% (week 1), 17.2% (week 2), 15.3% (week 4) | Pruritus—41.6% (week 1), 18.8% (week 2), 17.8% (week 4) | |
Paller et al. [58] | Three prospective, multicenter, randomized, investigator-blinded, comparative studies | Mi-very sev AD (IGADA score; ≥ 5% total BSA), ≥ 2 years, N = 1065 | 1:1 PIM, 1% vs. TAC, 0.03% or 0.1% BID for up to 6 weeks | Burning—10.9% (TAC combined groups, n = 58), 9.6% (PIM, n = 51); significant difference in adults [19.5% (TAC 0.1%, adult group, n = 41), 11.3% (PIM, n = 23), p = 0.02] Pain—2.1% (TAC combined groups, n = 11), 1.5% (PIM, n = 8) | Pruritus—7.0% (TAC combined groups, n = 37), 7.1% (PIM, n = 38) | Local ASRs most common AEs |
Schachner et al. [44] | Multicenter, randomized, DB, vehicle-controlled study | Mi-mod AD (IGADA score; 2–30% total BSA), 2–15 years, N = 317 | 1:1 TAC, 0.03% vs. VEH BID for up to 6 weeks | Burning/stinging—19.0% (TAC, n = 30), 17.0% (VEH, n = 27) | Pruritusc—23.4% (TAC, n = 37)f, 33.3% (VEH, n = 53) | Discontinuation due to AS AE—2.5% (TAC)f, 7.5% (VEH) |
Eichenfield et al. [28] | Three multicenter, DB, vehicle-controlled studies | Mi-mod AD (IGA score of 2 or 3; ≥ 5% total BSA), 3 months to 17 years, N = 589 | 2:1 PIM, 1% vs. VEH BID for 6 weeks | Burning—9.0% (White, PIM), 5.6% (non-White, PIM), 9.1% (White, VEH), 10.1% (non-White, VEH) | ||
Kaufman et al. [25] | Randomized, DB, parallel-group, vehicle-controlled, multicenter study | Mi-mod AD (IGA score of 2 or 3; ≥ 5% total BSA), 18–81 years, N = 198 | 1:1 PIM, 1% vs. VEH BID for 7 days, followed by optional 5-week OL extension | Burning—3.0% (n = 3, PIM) 1.0% (n = 1, VEH) Discontinuation due to burning—1.0% (n = 1, VEH) | ||
Lubbe et al. [35] | OL, single-arm, multicenter, prospective study | AD of any severity (IGA score), 3 months to 81 years, N = 947 | PIM, 1% BID for up to 6 months as part of treatment regimen; TCS for flares | Burningb—7.0% Discontinuation due to severe burning—0.5% | Pruritus—4.6%, considered treatment-related in 2.9% of patients Discontinuation due to pruritus—0.1% (n = 1) | |
Simon et al. [36] | OL, single-arm, multicenter study | AD of any severity (IGA score), 6 months to 70 years, N = 109 | PIM, 1% BID for up to 6 months, TCS for flares; emollients and antimicrobial agents permitted | Burning—6.4% (n = 7), AE most likely to be considered treatment-related | ||
Singalavanija et al. [45] | Multicenter, OL study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 10% total BSA), 2–12 years, N = 61 | TAC, 0.03% BID for up to 4 weeks | Burning—23% (n = 14) | Pruritus—16.4% (n = 10) | |
Reitamo et al. [49] | Multicenter, noncomparative, phase 3/4 study | AD [none (0.3%), mild (8.2%), moderate (65.5%), severe (26.0%)], 18–85 years, N = 672 | TAC, 0.1% BID for 3 weeks, then QD until clearance, for up to 24 months. TAC BID for 3 weeks in event of flare | Burninge—31.7% (n = 213)c Discontinuation due to burning—1.2% (n = 8), most common reason for discontinuation | Prurituse—11.3% (n = 76)c | |
Remitz et al. [50] | Long-term, OL, noncomparative, multicenter, phase 3b study | Mod-sev AD (Rajka and Langelanda criteria), 2–15 years, N = 466 | TAC, 0.03% or 0.1% BID prn for up to 29.5 months | Burningc—28.1% (TAC combined, n = 131), considered treatment-related in 124 patients (26.6%) | Pruritusc—30.3% (TAC combined, n = 141), considered treatment-related in 123 patients (26.4%) | Discontinuation due to unspecified AS AEse—3.0% (n = 14) |
Murrell et al. [26] | Multicenter, randomized, DB, vehicle-controlled; followed by OL extension study | Mi-mod head and neck (facial) AD (IGA score of 2 or 3), ≥ 12 years, N = 200 | 1:1 PIM, 1% vs. VEH BID for up to 6 weeks (DB); followed by optional PIM BID for up to 6 weeks (OL) | Pain (DB)c—8.9% (PIM, n = 9), 13.1% (VEH, n = 13) Irritation (DB)c—26.7% (PIM, n = 27), 22.2% (VEH, n = 22) | Pruritus (DB)c—8.9% (PIM, n = 9), 5.1% (VEH, n = 5) | Paresthesia (DB)c—4.0% (PIM, n = 4), 3.0% (VEH, n = 3) Warmth (DB)c—13.9% (PIM, n = 14), 11.1% (VEH, n = 11) Discontinuation due to AS pain/erythema/pruritus/dermatitis (DB)—4.0% (PIM, n = 4), 4.0% (VEH, n = 4) |
Fleischer et al. [59] | Prospective, multicenter, randomized, investigator-blinded, comparative study | Mod-very sev AD (IGADA score; ≥ 5% total BSA), ≥ 16 years, N = 281 | 1:1 TAC, 0.1% vs. PIM, 1% BID for up to 6 weeks | Burningb—19.9% (TAC, n = 28), 12.9% (PIM, n = 18) Painb—2.1% (TAC, n = 3), 0.7% (PIM, n = 1) Discontinuation due to AS burning—0.7% (TAC, n = 1), 0.7% (PIM, n = 1) | Pruritusb—7.8% (TAC, n = 11), 5.7% (PIM, n = 8) Discontinuation due to AS pruritus—0.7% (TAC, n = 1) | Warmthb—2.1% (TAC, n = 3), 0.7% (PIM, n = 1) |
Zuberbier et al. [29] | Multicenter, DB, randomized, vehicle-controlled, parallel-group study | History of sev AD (Rajka and Langelanda score of 8 or 9), 2–17 years, N = 184 | 2:1 PIM, 1% vs. VEH BID for up to 24 weeks; prednicarbate cream, 0.25% for flares | Skin burninge—1.0% (PIM, n = 2), 1.1% (VEH, n = 1) | ||
Wollenberg et al. [52] | Multicenter, randomized, vehicle-controlled, phase 3 study | Mi-sev AD (Rajka and Langelanda score ≥ 3), ≥ 16 years, N = 257 | TAC, 0.1% BID for up to 6 weeks (OL period), followed by TAC, 0.1% or VEH QD twice weekly for 12 months (DB period); TAC, 0.1% applied BID for up to 6 weeks during DB period if disease exacerbation | Irritationc—32.3% (n = 83, OL) Irritationc—5.2% (TAC, n = 6, DB); 6.5% (VEH, n = 7, DB) | Pruritusc—17.9% (TAC, n = 46, OL) Pruritusc—11.2% (TAC, n = 25, DB); 11.1% (VEH, n = 12, DB) | Warmthc—7.0% (TAC, n = 18, OL) |
Zuberbier and Brautigam [30] | Multicenter, randomized, DB, parallel-group, vehicle-controlled, multicenter study | Mi-mod facial AD (IGA score of 1–3), 2–17 years, N = 140 | 1:1 PIM, 1% or VEH BID for up to 24 weeks; prednicarbate cream, 0.25% for flares | Burninge—1.3% (PIM, n = 1), 1.6% (VEH, n = 1) | ||
Sigurgeirsson et al. [31] | Multicenter randomized, DB, parallel-group, comparative, vehicle-controlled study | History of mi-mod AD (IGA score of 2 or 3), 2–17 years, N = 521 | 1:1 PIM, 1% vs. VEH BID for up to 26 weeks; TCS for flares | Burninge—1.2% (PIM, n = 3), 3.1% (VEH, n = 8) | ASRs were most common events leading to discontinuations in both groups | |
Thaci et al. [53] | Multicenter, randomized, vehicle-controlled, phase 3 study | Mi-sev AD (Rajka and Langelanda score ≥ 3), 2–15 years, N = 267 | TAC, 0.03% BID for up to 6 weeks (OL period), followed by TAC, 0.03% or VEH QD twice weekly for 12 months (DB period); TAC, 0.1% applied BID for up to 6 weeks during DB period if disease exacerbation | Irritationc—6.0% (TAC, n = 16, OL) | Pruritusc—14.2% (TAC, n = 38, OL) Pruritusc—47.2% (TAC, n = 9, DB), 9.6% (VEH, n = 12, DB) | |
Ring et al. [37] | Multicenter, naturalistic, OL study | Mi-mod AD (IGA score ≥ 1), ≥ 3 months, N = 2034 | PIM, 1% BID for up to 12 months, TCS for flares | Burningc,e—6.8% | Unspecified ASRs considered treatment-related in 7.4% of patients | |
Paller et al. [56] | Randomized, 2-phase, multicenter study | Mod-sev AD (PSGA score ≥ 3), 2–15 years, N = 206 | Phase 1 acute (DB): 1:1 TAC, 0.03% vs. alclometasone ointment, 0.05% for 4 days Phase 1 short-term (OL): TAC, 0.03% BID for up to 16 weeks Phase 2 (DB): 1:1 TAC, 0.03% vs. VEH, QD 3 times/week for up to 40 weeks Phase 2 relapse (OL): TAC, 0.03% BID for up to 8 weeks | Burning—9.2% (TAC, n = 9, phase 1 acute, DB), 8.7% (alclometasone, n = 9, phase 1 acute, DB); 12.2% (TAC, n = 12, phase 1 short-term, OL, week 2), 9.7% (alclometasone/TAC, n = 10, phase 1 short-term, OL, week 2); 2.9% (TAC, n = 2, phase 2, DB), 2.8% (VEH, n = 1, phase 2, DB); 2.7% (TAC, n = 2, phase 2 relapse, OL) Irritation—0% (TAC, n = 0, phase 1 acute, DB), 1.0% (alclometasone, n = 1, phase 1 acute, DB); 0% (TAC, n = 0, phase 1 short-term, OL, week 2), 1.0% (alclometasone/TAC, n = 1, phase 1 short-term, OL, week 2); 1.5% (TAC, n = 1, phase 2, DB), 0% (VEH, n = 0, phase 2, DB); 0% (TAC, n = 0, phase 2 relapse, OL) | Pruritus—6.1% (TAC, n = 6, phase 1 acute, DB), 3.9% (alclometasone, n = 4, phase 1 acute, DB); 6.1% (TAC, n = 6, phase 1 short-term, OL, week 2), 9.7% (alclometasone/TAC, n = 10, phase 1 short-term, OL, week 2); 1.5% (TAC, n = 1, phase 2, DB), 5.6% (VEH, n = 2, phase 2, DB); 0% (TAC, n = 0, phase 2 relapse, OL) | |
Langley et al. [39] | OL extension study of 2 multicenter, randomized, DB, phase 3 studies | Mi-mod AD (IGA score of 2 or 3; ≥ 5% total BSA), 2–17 years, N = 403 | 2:1 PIM, 1% vs. VEH for 6 weeks (DB), followed by PIM, 1% BID for 20 weeks (OL) | Burningc—10.5% (PIM, DB), 13.2% (VEH, DB), 2.6% (PIM/PIM, OL), 2.0% (VEH/PIM, OL) | ||
Abramovits et al. [60] | Multicenter, prospective, randomized, investigator-blinded, comparative study | Mod AD (IGADA score; ≥ 5% total BSA), ≥ 16 years, N = 188 (TAC, n = 8; PIM, n = 90) | 1:1 TAC, 0.1% vs. PIM, 1% BID for up to 6 weeks | Burningb—19.4% (TAC, n = 19), 13.3% (PIM, n = 12) Painb—3.1% (TAC, n = 3), 0% (PIM, n = 0) | Pruritusb—9.2% (TAC, n = 9), 5.6% (PIM, n = 5) | Warmthb—2.0% (TAC, n = 2), 1.1% (PIM, n = 1) |
Reitamo et al. [51] | Multicenter, noncomparative, OL study | AD (5–60% total BSA for ages 2–15 years and ≥ 5% total BSA for ages ≥ 16 years), 2–72 years, N = 782 | TAC, 0.1% BID for up to 48 months | Burningb,d—37.3% (n = 292) | Pruritusb,d—15.9% (n = 124) | Most frequent ASRs were skin burning and pruritus |
Breneman et al. [55] | Randomized, multicenter study | Mod-sev AD (PSGA score ≥ 3), ≥ 2 years, N = 383 | Phase 1 acute (DB): 1:1 TAC, 0.03% or 0.1% vs. alclometasone ointment, 0.05% for 4 days Phase 1 short-term (OL): TAC, 0.03% or 0.1% BID for up to 16 weeks Phase 2 (DB): 1:1 TAC, 0.03% or 0.1% vs. VEH QD 3 times/week for up to 40 weeks Phase 2 relapse (OL): TAC, 0.03% or 0.1% BID for up to 8 weeks | Burning—10.1% (TAC, n = 19, phase 1 acute, DB), 5.3% (alclometasone, n = 10, phase 1 acute, DB); 12.2% (TAC, n = 23, phase 1 short-term, OL), 8.5% (alclometasone/TAC, n = 16, phase 1 short-term, OL); 1.6% (TAC, n = 2, phase 2, DB), 1.4% (VEH, n = 1, phase 2, DB); 3.2% (TAC, n = 4, phase 2 relapse, OL) Irritation—0% (TAC, n = 0, phase 1 acute, DB), 0.5% (alclometasone, n = 1, phase 1 acute, DB); 0% (TAC, n = 0, phase 1 short-term, OL), 1.1% (alclometasone/TAC, n = 2, phase 1 short-term, OL); 1.6% (TAC, n = 2, phase 2, DB), 0% (VEH, n = 0, phase 2, DB); 0% (TAC, n = 0, phase 2 relapse, OL) | Pruritus—6.4% (TAC, n = 12, phase 1 acute, DB), 2.6% (alclometasone, n = 5, phase 1 acute, DB); 7.4% (TAC, n = 14, phase 1 short-term, OL), 9.0% (alclometasone/TAC, n = 17, phase 1 short-term, OL); 0.8% (TAC, n = 1, phase 2, DB), 2.8% (VEH, n = 2, phase 2 DB); 0.8% (TAC, n = 1, phase 2 relapse, OL) | |
De Backer et al. [38] | Multicenter, single-arm, observational, OL study | Mi-mod AD (IGA score), ≥ 2 years, N = 416 | PIM, 1% BID prn for up to 1 year; emollients and TCS permitted | ASRs (burning, irritation, erythema, pruritus, stinging, pain, paresthesia vesicular eruption)b—46.5% of AEs, 95% considered treatment-related, 50% mild, 35% moderate, 15% severe Drug discontinuation due to ASR—24.2% of reported AEs | ||
Hoeger et al. [27] | Randomized, DB, multicenter study; followed by 6-week OL extension | Mi-mod facial AD (IGA score of 2 or 3), 2–11 years, N = 200 | 1:1 PIM, 1% vs. VEH BID to the face, head, and neck and prn to other affected areas for up to 6 weeks, followed by PIM, 1% BID prn to all affected areas for up to 6 weeks | Irritation—5.1% (PIM, n = 5, DB), 5.0% (VEH, n = 5, DB) | Discontinuation due to AS erythema/irritation—1.0% (VEH, n = 1) ASRs were most common treatment-related AEs in both groups | |
Ruer-Mulard et al. [40] | Multicenter OL study; followed by randomized, DB, multicenter study | Mi-sev AD (IGA score ≥ 2; ≥ 5% total BSA), 2–17 years, N = 300 | PIM, 1% BID for up to 6 weeks (OL), followed by 1:1 PIM, 1% BID vs. PIM, 1% QD for up to 16 weeks (DB); TCS permitted for disease exacerbation | Discontinuation due to irritation—0.3% (PIM, n = 1, OL)e | Discontinuation due to pruritus—0.3% (PIM, n = 1, OL), treatment-related; 0.7% (PIM BID, n = 1, DB) | |
Kirsner et al. [61] | Three prospective, multicenter, randomized, comparative studies | Mi-very sev AD (IGADA score; ≥ 5% total BSA), ≥ 2 years, N = 347 | 1:1 PIM, 1% vs. TAC, 0.03% or 0.1% BID for up to 6 weeks | Burningb—9.9% (TAC combined, n = 17), 14.2% (PIM, n = 25) Pain—4.1% (TAC combined, n = 7), 1.7% (PIM, n = 3) | Pruritusb—7.0% (TAC combined, n = 12), 10.2% (PIM, n = 18) | Warmth—1.2% (TAC combined, n = 2), 0% (PIM, n = 0) |
Meurer et al. [23] | Randomized, multicenter, parallel-group, vehicle-controlled study | Sev AD (IGA score ≥ 4.0; ≥ 5% total BSA, excluding the face), 2–17 years, N = 376 | 1:1 PIM, 1% and TCS (FP, 0.05% or HA, 1% for the face, neck, and intertriginous areas) vs. VEH and TCS BID for 4 weeks followed by 12 weeks of observation period in which no drug was administered | Burningd—1.6% (PIM + TCS, n = 3), 1.4% (VEH + TCS, n = 2) | Exacerbation of pruritusd—0.0% (PIM + TCS, n = 2), 0.6% (VEH + TCS, n = 1) | |
Reitamo et al. [54] | Two randomized, multicenter, comparative, phase 3 studies | Mod-sev AD (Rajka and Langelanda criteria), ≥ 2 years, N = 349 | TAC, 0.03% or 0.1% BID for up to 6 weeks (OL), followed by 1:1 TAC, 0.03% or 0.1% vs. VEH, QD twice/week for up to 12 months (DB); TAC, 0.03% or 0.1% BID for up to 6 weeks in the event of a flare during the DB period | Irritatione—5.0% (TAC, n = 4, adults, DB), 3.8% (TAC, n = 3, children, DB), 8.2% (VEH, n = 6, adults, DB), 1.3% (VEH, n = 1, children, DB) | Prurituse—11.3% (TAC, n = 9, adults, DB), 10.3% (TAC, n = 8, children, DB), 12.3% (VEH, n = 9, adults, DB), 10.7% (VEH, n = 8, children, DB) | ASRs were most common treatment-related AEs in OL and DB phases |
References | Study design | Patient characteristics | Treatment and duration | Frequency of application site burning, stinging, pain, discomfort | Frequency of application site pruritus, erythema | Frequency of application site paresthesia, other |
---|---|---|---|---|---|---|
Faergemann et al. [68] | Multicenter, OL study | AD [combined assessment score rating erythema, infiltration, and lesion number from 0 (none) to 3 (severe) ≥ 7], 17–63 years, N = 68 | MF fatty cream, 0.1% twice weekly for 6 months following run-in period of MF fatty cream, 0.1% QD for 3 weeks | Warmtha—1.5% (n = 1) | ||
Cato et al. [70] | Multicenter, randomized, DB, active and vehicle-controlled study | AD [total score rating erythema, induration, and pruritus each from 0 (absent) to 6 (markedly severe) ≥ 7 for ≥ 2 of 3 test lesions], 18–86 years, N = 150 | 1:1:1 TA vs. TNX vs. VEH BID for 2 weeks | Local burning, pruritus, or disease exacerbationb—6% (n = 3, TNX), 4% (n = 2, TA), 12% (n = 6, VEH) | ||
Paller et al. [71] | Multicenter, randomized, DB, vehicle-controlled study (study 1); multicenter, OL, cortisol-stimulation study (study 2); OL allergen reactivity study (study 3) | AD [≥ 20% total BSA (study 1), ≥ 50% total BSA (study 2), ≥ 20% total BSA with confirmed peanut allergy (study 3)]; 2–12 years; N = 94 (study 1), N = 32 (study 2), N = 9 (study 3) | FA in peanut oil, 0.01% or peanut oil VEH BID to areas other than the face and intertriginous sites for 2 weeks followed by FA in peanut oil, 0.01% BID for 2 weeks, followed by peanut oil VEH BID for 2 weeks (study 1); FA in peanut oil, 0.01% BID for 4 weeks over ≥ 50% BSA (study 2); FA in peanut oil, 0.01% or peanut oil VEH prick and patch testing then FA in peanut oil, 0.01% BID to areas other than the face for 1 week (study 3) | Mild itching and burning—3.1% (n = 1, FA, study 2) | ||
Friedlander et al. [20] | Phase 4, multicenter, OL safety study | Mod-sev AD [total severity score ≥ 6.0 for any 3 of 8 signs/symptoms (erythema, pruritus, papulation, induration, oozing/crusting, scaling, excoriation, lichenification) rated from 0 (absent) to 3 (severe); ≥ 35% total BSA, excluding diaper area, eyelids, perioral area, nostrils, and TCS contraindicated locations], 3 months to 5 years, 11 months, N = 51 | FP cream, 0.05% BID to all lesions except diaper area, eyelids, perioral area, nostrils, and TCS contraindicated locations for up to 4 weeks | Burninga—2.0% (n = 1) | ||
Kirkup et al. [63] | Two multicenter, randomized, DB, parallel-group studies | Mod-sev AD flare with total AD score [no. of affected body areas (max 12) + sum of erythema, excoriation, and lichenification scores (each rated from mild (0) to severe (3)) for the target area (defined as particularly troublesome site; max score = 9)] ≥ 6 (max = 21); 2–14 years; N = 137 (study 1), N = 128 (study 2) | FP cream, 0.05% or HC cream, 1% BID for 2–4 weeks then prn (up to BID) for 3 months (study 1); FP cream, 0.05% or HCB cream, 0.1% BID for 2–4 weeks then prn (up to BID) for 3 months (study 2); emollients permitted | Pruritusa—3.2% (n = 2, HCB, study 2) | ||
Eichenfield et al. [64] | Two multicenter, randomized, DB, vehicle-controlled studies | Mod-sev AD (Rajka and Langelandc score > 4), 3 months to 87 years, N = 438 | FP lotion, 0.05% or VEH QD for 4 weeks to affected areas except the eyelids, perioral area, nostrils, and diaper area | Burning/stinginga,d—1.8% (n = 4, FP), 1.4% (n = 3, VEH) | Pruritusa,d—0.5% (n = 1, FP), 0.5% (n = 1, VEH) | |
Hebert et al. [19] | Two phase 3, randomized, DB, vehicle-controlled studies | Mi-mod AD (IGSS score; ≥ 10% total BSA), 3 months to 18 years, N = 582 | Desonide hydrogel, 0.05% or VEH BID for 4 weeks | Burninge—1% (desonide), not stated (VEH) | Prurituse—1% (desonide), not stated (VEH) | AS events (unspecified)—3% (desonide), incident rate not higher than VEH |
Matheson et al. [66] | Multicenter, randomized, DB, parallel-group, vehicle-controlled study | Mi-mod AD (PGA score of 2 or 3; ≥ 10% total BSA), 3 months to < 18 years, N = 284 | 1:1 HCB lotion, 0.1% vs. VEH BID for 4 weeks | Burning—1% (n = 1, HCB), 6% (n = 8, VEH)b,f | Pruritus—not stated (HCB), 3% (VEH) | |
Peserico et al. [69] | Multicenter, randomized, DB, vehicle-controlled, parallel-group study | 2-year history of mod-sev AD with severe or very severe acute flare (IGA ≥ 4), ≥ 12 years, N = 249 | MPA cream, 0.1% QD + emollient for up to 4 weeks (acute, OL) then 1:1 MPA, 0.1% QD twice weekly + emollient BID 5 times weekly: emollient BID, for 16 weeks (maintenance, DB) | Burninga,d—1% (n = 1; MPA, during entire study) | ||
Hebert et al. [67] | One phase 2, multicenter, OL HPA axis safety study, one phase 2 safety/efficacy study, and one phase 3 safety/efficacy study | Mi-mod AD (ISGA score of 2 or 3; ≥ 25% total treatable BSA); 3 months to < 18 years; N = 81 (phase 2 OL), N = 768 (3 combined safety/efficacy studies) | Desonide foam, 0.05% BID for 4 weeks (OL), 2:1 desonide vs. VEH BID for 4 weeks (combined safety/efficacy studies) | Burning (combined safety/efficacy studies)b,e—3% (n = 14, desonide), 7% (n = 16, VEH)f | Pruritus (combined safety/efficacy studies)—0% (n = 2, desonide), 0% (n = 0, VEH) | |
Abramovits et al. [65] | Phase 3, multicenter, randomized, DB, vehicle-controlled study | Mi-mod AD (PGA score of 2 or 3; ≥ 10% total BSA), 3 months to < 18 years, N = 264 | HCB lipocream, 0.1% or vehicle BID for up to 1 month | Irritationa—1% (n = 1, HCB), 0% (n = 0, VEH) |
References | Study design | Patient characteristics | Treatment and duration | Frequency of application site burning, stinging, pain, discomfort | Frequency of application site pruritus, erythema | Frequency of application site paresthesia, other |
---|---|---|---|---|---|---|
Reitamo et al. [78] | Phase 3, comparative, multicenter, DB, parallel-group study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 5% total BSA), 16–70 years, N = 570 | 1:1:1 TAC, 0.03% vs. TAC, 0.1% vs. HCB ointment, 0.1% BID for 3 weeks | Burning—12.9% (n = 24, HCB), 59.2% (n = 113, TAC, 0.1%)b, 45.1% (n = 87, TAC, 0.03%)b | Pruritus—9.7% (n = 18, HCB), 15.2% (n = 29, TAC, 0.1%)b, 20.2% (n = 39, TAC, 0.03%)b | Discontinuation due to serious, treatment-related AS burning and pruritus—0.5% (n = 1, TAC 0.1%) |
Reitamo et al. [73] | Phase 3, comparative, multicenter, randomized, DB, parallel-group study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 5 – ≤ 60% total BSA), 2–15 years, N = 560 | 1:1:1 TAC, 0.03% vs. TAC, 0.1% vs. HA ointment, 0.1%, BID for up to 3 weeks | Burningc—7.0% (HA, n = 13), 18.5% (TAC, 0.03%, n = 35)b, 20.4% (TAC, 0.1%, n = 38)b Discontinuation due to skin burning and paind—0.5% (TAC, 0.03%, n = 1) | Pruritusc—7.6% (HA, n = 14), 13.2% (TAC, 0.03%, n = 25), 11.3% (TAC, 0.1%, n = 21) Discontinuation due to pruritusd—0.5% (TAC, 0.03%, n = 1) | |
Reitamo et al. [74] | Randomized, DB, multicenter comparative study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 5% total BSA), 2–15 years, N = 624 | 1:1:1 TAC, 0.03% QD vs. TAC, 0.03% BID vs. HA ointment BID for 3 weeks | Burninge—14.5% (n = 30, HA), 23.2% (n = 48, TAC QD)b, 23.8% (n = 50, TAC BID)b Discontinuation due to burningd—0.5% (n = 1, TAC BID) Discontinuation due to burning and pruritusd—0.5% (n = 1, TAC QD) | Prurituse—15.9% (n = 33, HA), 18.4% (TAC QD, n = 38), 21.4% (TAC BID, n = 45) | |
Luger et al. [72] | Multicenter, randomized, DB, parallel-group study | Mod-sev AD (Rajka and Langelanda criteria; ≥ 5% total BSA), 18–79 years, N = 658 | 1:1 PIM, 1% vs. TA cream, 0.1% (trunk/limbs) and HA cream, 1% (face, neck, intertriginous areas), BID for up to 1 years | Burningc—25.9% (PIM, n = 85), 10.9% (TA + HA, n = 36) Irritation—6.4% (PIM, n = 21), 3.3% (TA + HA, n = 11) | Pruritus—5.5% (PIM, n = 18), 1.8% (TA + HA, n = 6) | Discontinuation due to ASR (unspecified)—7.6% (PIM), 0.9% (TA + HA) ASRs (unspecified) were the AEs most likely to lead to discontinuation in both groups |
Reitamo et al. [76] | Randomized, DB, comparative, multicenter, phase 3 study | Mod-sev AD (Rajka and Langelanda score ≥ 4.5), ≥ 18 years, N = 972 | 1:1 TAC, 0.1% vs. HCB ointment, 0.1% (trunk/limbs) and HA ointment, 1% (head/neck), BID for up to 6 months | Burningc—13.8% (HCB + HA, n = 67), 52.4% (TAC, n = 255)b | Pruritusc—13.4% (HCB + HA, n = 65), 18.1% (TAC, n = 88) | Skin tinglingc—0.6% (HCB + HA, n = 3), 2.7% (TAC, n = 13)b Treatment-related, AS irritation events (unspecified) made up most of the discontinuations due to an AE |
Bieber et al. [77] | Randomized, DB, comparative, multicenter study | Sev-very sev flare of AD (IGA score ≥ 4), 2–15 years, N = 265 | 1:1 MPA ointment, 0.1%, QD vs. TAC, 0.03% BID for up to 3 weeks | Incidence of treatment-related AEs (unspecified)d—0% (MPA, n = 0), 4.4% (TAC, n = 6, pruritus, erythema, skin burning, and hot flushes) Discontinuations due to AEsd—0% (MPA, n = 0), 2.9% [TAC, n = 4, treatment-related pruritus (n = 1), treatment-related pruritus/skin burning (n = 1), treatment-related pruritus/hot flushes (n = 1), scarlet fever (n = 1; not treatment-related)] | ||
Doss et al. [80] | Multicenter, randomized, DB, phase 4 study | Mod-sev facial AD (Rajka and Langelanda score of 4.5–9; facial BSA ≥ 10%), ≥ 16 years, N = 568 | 1:1 TAC, 0.1% vs. fluticasone ointment, 0.005% (facial lesions), or OL fluticasone ointment, 0.005% (all other lesions) BID for up to 3 weeks, followed by a second 3-week period of no study treatment, QD study treatment, or BID treatment with the other drug | Burning sensationd,e—16.0% (TAC, n = 46, face), 0.3% (TAC, n = 1, nonfacial), 2.9% (fluticasone, n = 8, face), 0.4% (fluticasone, n = 1, nonfacial) | Pruritusd,e—3.1% (TAC, n = 9, face), 1.0% (TAC, n = 3, nonfacial), 2.2% (fluticasone, n = 6, face), 1.1% (fluticasone, n = 3, nonfacial) | Most AEs in both groups were ASRs |
Doss et al. [79] | Multicenter, DB, randomized, noninferiority study | Mod-sev AD unresponsive to TCS (Rajka and Langelanda score ≥ 4.5), 2–15 years, N = 479 | 1:1 TAC, 0.03% vs. fluticasone ointment, 0.005% BID for up to 3 weeks to all lesions except eyelids, with optional additional 3 weeks QD treatment | Burning sensatione—7.6% (TAC, n = 18), 2.5% (fluticasone, n = 6) | Pruritusd,e—4.2% (TAC, n = 10), 3.3% (fluticasone, n = 8) | AS AEs (unspecified)—days 1–21: 18.0% (TAC, n = 43)b, 11.3% (fluticasone, n = 27); days 21–42: 4.1% (TAC, n = 9), 1.3% (fluticasone, n = 3) |
Rahman et al. [75] | Randomized controlled trial | AD [mean EASI at baseline 11.29 (TAC), 11.05 (HA)], 2–10 years, N = 60 | 1:1 TAC, 0.03% vs. HA ointment, 1% BID for 3 weeks | Burning sensationd—23.3% (TAC, n = 7), 3.3% (HA, n = 1) | Localized pruritus—10.0% (TAC, n = 3), 3.3% (HA, n = 1) |
References | Study design | Patient characteristics | Treatment and duration | Frequency of application site burning, stinging, pain, discomfort | Frequency of application site pruritus, erythema | Frequency of application site paresthesia, other |
---|---|---|---|---|---|---|
Paller et al. [21] | Two phase 3, multicenter, randomized, vehicle-controlled, DB studies | Mi-mod AD (ISGA score of 2 or 3; ≥ 5% treatable BSA), 2–79 years, N = 1522 | 2:1 Crisaborole ointment, 2% vs. vehicle BID to all affected areas except the scalp for 28 days | Pain (burning/stinging)a,b—4.4% (crisaborole, n = 45)c, 1.2% (VEH, n = 6) | Pruritus—0.5% (crisaborole, n = 5), 1.2% (VEH, n = 6) | |
Eichenfield et al. [22] | Multicenter, OL extension of phase 3 studies | Mi-mod AD (ISGA score of 2 or 3), 2–72 years, N = 517 | Crisaborole ointment, 2% BID to all affected areas except the scalp for up to 52 weeks | Paina—2.3% (n = 12), 6 pain events (1.2%) occurred during 48-week long-term extension |