Table 1.
Study details for the RCTs included in the quantitative analyses of the efficacy and safety of topical treatments for moderate-to-severe papulopustular rosacea
| Study name/publication | Design | Duration (weeks) | Intervention (n) | Analysis outcomes | Author conclusions |
|---|---|---|---|---|---|
| 18170 Study (Gold et al. 2014a; Stein et al. 2014) Part A (efficacy) and Part B (safety) Additional data not included in Cochrane review from CSR |
R, DB, AP, MC-I, Phase III |
56 | Ivermectin 1 % cream QD (451) Azelaic acid 15 % gel BID (210) – Part B only Vehicle (232) |
Inflammatory lesion count Success rate Any AE, any TRAE, any SAE Specific AEs: burning/stinging, skin irritation, worsening of rosacea All cause withdrawals Withdrawal due to AE |
Ivermectin 1 % cream QD was well-tolerated and safe for papulopustular rosacea, in particular, no notable difference was found between the ivermectin 1 % cream QD and azelaic acid 15 % gel BID. Ivermectin 1 % cream QD resulted in fewer skin-related AEs than with azelaic acid 15 % gel BID and vehicle |
| 18171 study (Gold et al. 2014b; Stein et al. 2014) Part A (efficacy) and Part B (safety) Additional data not included in Cochrane review from CSR |
R, DB, AP, MC-I, Phase III |
56 | Ivermectin 1 % cream QD (459) Azelaic acid 15 % gel BID (208)—Part B only Vehicle (229) |
Inflammatory lesion count Success rate Any AE, any TRAE, any SAE Specific AEs: burning/stinging, skin irritation All cause withdrawals Withdrawal due to AE |
Ivermectin 1 % cream QD was well-tolerated and safe, with less frequent AEs and a statistically significantly greater success rate at 12 weeks compared to azelaic acid 15 % gel BID when used to treat moderate-to-severe papulopustular rosacea |
| Beutner and Calverese (2005) | R, IB, AP, MC, PU | 10 | MET 1 % cream QD (553) MET 1 % gel QD (557) Vehicle (189) |
Success rate | Metronidazole gel 1 % QD had a higher efficacy rate than its cream formulation and its vehicle and was equally well-tolerated for the treatment of rosacea |
| Bjerke et al. (1999) | R, DB, PC, MC, PU | 13 | Azelaic acid 20 % cream BID (76) Vehicle (39) |
Specific AEs: burning/stinging, skin irritation Withdrawal due to AE |
Azelaic acid 20 % cream BID was effective and well-tolerated with a significantly greater reduction inflammatory lesion count compared to vehicle for the treatment of papulopustular rosacea |
| Draelos et al. (2013) | R, DB, PC, MC, PU | 16 | Azelaic acid 15 % foam BID (198) Vehicle (203) |
Inflammatory lesion count Success rate Any TRAE Specific AEs: burning/stinging, worsening of erythema, worsening of rosacea All cause withdrawals Withdrawal due to AE |
Azelaic acid 15 % foam BID demonstrated a significant advantage over the vehicle in both primary measures of efficacy: therapeutic success rate (p = 0.017) and change in inflammatory lesion count (p = 0.001) for the treatment of papulopustular rosacea |
| Draelos et al. (2015) Not included in Cochrane review |
R, DB, PC, MC, Phase III | 16 | Azelaic acid 15 % foam BID (484) Vehicle (477) |
Inflammatory lesion count Success rate Any SAE All cause withdrawals Withdrawal due to AE |
This study supported the efficacy and safety of azelaic acid foam in patients with papulopustular rosacea. Azelaic acid 15 % foam demonstrated a statistically significant advantage over vehicle in both primary measures of efficacy success rate and change in inflammatory lesion count |
| Elewski et al. (2003) | R, IB, AC, MC, PU | 15 | Azelaic acid 15 % gel BID (124) MET 0.75 % gel BID (127) |
Inflammatory lesion count Success rate |
Use of azelaic acid 15 % gel for 15 weeks demonstrated significant superiority over using MET 0.75 % gel in improving principal signs of rosacea (inflammatory lesions and erythema) |
| Fowler (2007a, b) | R, DB, PC, MC, PU | 16 | MET 1 % gel BID + Vehicle followed by Vehicle (36) MET 1 % gel BID + DOX 40 mg QD followed by DOX 40 mg QD (36) |
Inflammatory lesion count | Combination anti-inflammatory dose DOX and MET 1 % gel resulted in a faster reduction of inflammatory lesion count, when calculated at all interim and final data analysis. Anti-inflammatory dose DOX sustained the reduction in lesion count through 16 weeks in patients with mild-to-moderate rosacea |
| Koca et al. (2010) | R, OL, AC, SC, PU | 12 | MET 1 % cream bid (24) PIM 1 % cream bid (25) |
All cause withdrawals | PIM 1 % cream was equally effective in reducing inflammatory lesion count as MET 1 % cream in the treatment of papulopustular rosacea |
| Leyden (2014) | R, DB, AP, MC, Phase II | 12 | Silica encapsulated benzoyl peroxide 1 % gel QD (32) Silica encapsulated benzoyl peroxide 5 % gel QD (30) Vehicle (30) |
Success rate | Silica encapsulated benzoyl peroxide 1 % and 5 % gels were superior to vehicle in reducing papulopustular lesions |
| NCT00617903 (2013) | R, DB, PC, MC, Phase II | 12 | Azelaic acid 15 % foam BID (41) Vehicle (42) |
Inflammatory lesion count Success rate Any AE Specific AEs: worsening of erythema, worsening of rosacea All cause withdrawals Withdrawal due to AE |
Authors’ conclusions about the study drug could not be ascertained from the NCT ID from where the trial data were extracted, no publication for the trial could be retrieved |
| RD.03.SRE.40027 (Galderma 2006) Additional data not included in Cochrane review from CSR |
R, IB, AP, MC-I, Phase II |
12 | Ivermectin 0.1 % cream QD (51) Ivermectin 0.3 % cream QD (47) Ivermectin 1 % cream BID (48) Ivermectin 1 % cream QD (52) MET 0.75 % cream BID (48) Vehicle (50) |
Inflammatory lesion count Success rate Any AE, any TRAE, any SAE Specific AEs: burning/stinging, skin irritation, worsening of erythema, worsening of rosacea All cause withdrawals Withdrawal due to AE |
Both ivermectin 1 % cream QD and BID were effective and safe, with similar efficacy results between the two dosages. Compliance was enhanced by the ivermectin 1 % QD application for the treatment of papulopustular rosacea |
| RD.03.SPR.40173 (ATTRACT) (Galderma 2014; Taieb et al. 2015a, b) Additional data not included in Cochrane review from CSR |
R, IB, AC, MC-I, Phase III |
52 | Ivermectin 1 % cream QD (478) MET 0.75 % cream BID (484) |
Inflammatory lesion count Success rate |
Ivermectin 1 % cream resulted in a statistically significant delayed and extended remission when compared to MET 0.75 % cream when used to treat papulopustular rosacea |
| Tan et al. (2002) | R, DB, PC, MC, PU | 12 | MET 1 % cream BID (61) Vehicle (59) |
Inflammatory lesion count Any AE, any TRAE Specific AEs: burning/stinging, worsening of erythema All cause withdrawals Withdrawal due to AE |
The combined topical formulation of MET 1 % cream with sunscreen SPF 15 was effective and well tolerated for the treatment of patients with moderate-to-severe rosacea |
| Thiboutot et al. (2003) | R, DB, PC, MC, Phase III | 12 | Azelaic acid 15 % gel BID (164) Vehicle (165) |
Inflammatory lesion count Success rate Any AE All cause withdrawals Withdrawal due to AE |
The results of these two controlled studies demonstrate that azelaic acid 15 % gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate papulopustular rosacea |
| Thiboutot et al. (2003) | R, DB, PC, MC, Phase III | 12 | Azelaic acid 15 % gel BID (169) Vehicle (166) |
Inflammatory lesion count Success rate Any AE All cause withdrawals Withdrawal due to AE |
|
| Thiboutot et al. (2008) | R, DB, DR, MC, PU | 12 | Azelaic acid 15 % gel BID (47) Azelaic acid 15 % gel QD (45) |
Inflammatory lesion count Success rate Any AE, any TRAE |
Once-daily azelaic acid 15 % gel can be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of azelaic acid 15 % gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist |
| Torok et al. (2005) | R, DB, AC, MC, PU | 12 | Sodium sulfacetamide 10 % cream BID + sulfur 5 % cream BID (75) MET 0.75 % cream BID (77) |
Inflammatory lesion count Any AE, any TRAE All cause withdrawals |
In patients without sulfur drug allergies, sodium sulfacetamide 10 % and sulfur 5 % cream with sunscreen offers greater efficacy than MET 0.75 % cream and has the added benefit of sun protection |
| Wolf et al. (2006) | R, IB, AC, MC, PU | 15 | Azelaic acid 15 % gel BID (78) MET 1 % gel QD (82) |
Success rate | MET 1 % gel and azelaic acid 15 % gel showed similar reductions in inflammatory lesion count and high success rates in both global severity and erythema in patients with moderate rosacea |
AC active-controlled, AE adverse events, AP active- and placebo/vehicle-controlled, BID twice daily, DB double-blind, DOX doxycycline, DR dose ranging, IB investigator blind, MC multicenter, MC-I multicenter international, MET metronidazole, N number of patients, PC placebo/vehicle-controlled, PIM pimecrolimus, PU phase unclear, QD once-daily, R randomized, SAE serious adverse event, SPF sun protection factor, TRAE treatment-related adverse event