An empirically generated responder definition for rosacea treatment

Figures & data

Table 1 Characteristics of 8 studies for the treatment of papulopustular rosacea

Clinical phase	II	III	III	III	IIIB	IIIB	III	IV
Study period	12/2009–8/2010	1/2001–7/2001	2/2001–6/2001	10/2001–5/2002	1/2004–12/2004	12/2006–6/2007	9/2012–1/2014	2/2009–7/2009
Study design	Double-blind, randomized	Double-blind, randomized	Double-blind, randomized	Double-blind, randomized	12-week open-label + 24-week double-blind	Double-blind, randomized	Double-blind, randomized	Investigator-blind, randomized
Number of centers	20	15	14	15	14	7	49	17
Treatment	Azelaic acid foam, 15%	Azelaic acid gel, 15%	Azelaic acid gel, 15%	Azelaic acid gel, 15%	Azelaic acid gel, 15% + doxycycline oral	Azelaic acid gel, 15%	Azelaic acid foam, 15%	Azelaic acid gel, 15%
Dose of treatment	0.5 g foam, BID	0.5 g gel, BID	0.5 g gel, BID	0.5 g gel, BID	0.5 g gel, BID, doxycycline 100 mg	0.5 g gel, OPD	0.5 g foam, BID	0.5 g gel, BID + doxycycline 40 mg
Comparator	Vehicle	Vehicle	Vehicle	Metronidazole gel, 0.75%, OPD	24 weeks vs vehicle	0.5 g gel, BID	Vehicle	Metronidazole gel, 1% OPD + doxycycline 40 mg OPD p.o.
Treatment duration (weeks)	12	12	12	15	12 + 24	12	12	12
N (treatment/comparator)	401 (198/204)	329 (164/165)	335 (169/166)	251 (124/127)	172; 136 (61/65)	92 (45/47)	961 (484/477)	207 (106/101)
Mean age (years)	48.5	48.6	47.3	47.5	46.6; 46.4	49	51.5	49.5
Gender
Female (%)	74.3	76	72	67.7	75; 74.3	69.6	73.0	65.7
Male (%)	25.7	24	28	32.3	25; 25.7	30.1	27.0	34.3
Reference	12	6	6	7	8	9	10	11

Abbreviations: BID, twice a day; OPD, once per day; p.o., orally.

Table 2 Numerical score and definitions of rosacea severity and definition of “responders” and “nonresponders”

Numerical score	Definition	Description	Responder definition
0	Clear	No papules and/or pustules; no or residual erythema; no or mild to moderate telangiectasia	Clear/minimal = treatment success: responder
1	Minimal	Rare papules and/or pustules; residual to mild erythema; mild to moderate telangiectasia
2a,b	Mild Mild to moderate	Few papules and/or pustules; mild erythema; mild to moderate telangiectasia Distinct number of papules and/or pustules; mild to moderate erythema; mild to moderate telangiectasia	Mild to severe = treatment failure: nonresponder
3a,c	Moderate Moderate to severe	Pronounced number of papules and/or pustules; moderate erythema; mild to moderate telangiectasia Many papules and/or pustules, occasionally with large inflamed lesions; moderate erythema; moderate degree of telangiectasia
4	Severe	Numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate or severe erythema; moderate or severe telangiectasia

Notes:

a Historical intermediate score, used in older studies.

b For our analyses, this category has been mapped to IGA category 3 “moderate.”

c For our analyses, this category has been mapped to IGA category 4 “severe.”

Abbreviation: IGA, Investigator Global Assessment.

Table 3 Subject demographics at baseline (n=2,748)

Variable	N (%)
Gender
Female	1,982 (72.1)
Male	766 (27.9)
Age group (years; mean ± SD)	49.3±12.5
BMI (kg/m^2; mean ± SD)	29.7±7.0
Ethnic group
Caucasian	2,599 (94.6)
Hispanic	56 (2.0)
Black	28 (1.0)
Asian	25 (0.9)
Others	23 (0.8)
Not reported	17 (0.6)

Abbreviation: BMI, body mass index.

Table 4 Lesion count by IGA 5-point scale

IGA score	Na	Mean	SD	Median	IQR
Clear	536	0.20	0.75	0	[0 to 0]
Minimal	1,924	2.81	2.50	2	[1 to 4]
Mild	3,012	6.73	4.50	6	[4 to 9]
Moderate	6,078	15.14	8.94	14	[9 to 19]
Severe	860	28.40	14.66	26	[18 to 36]

Note:

a All observations (multiple observations per subject possible).

Abbreviations: IGA, Investigator Global Assessment; IQR, interquartile range.

Table 5 Lesion count change from baseline by IGA change from baseline

Change in IGA score	Na	Mean	SD	Median	IQR
Improved by 4 scores	92	−21.20	9.21	−19	[−25.5 to −14.0]
Improved by 3 scores	619	−18.01	9.23	−15	[−20.0 to −12.0]
Improved by 2 scores	1,904	−15.79	8.00	−14	[−19.0 to −10.0]
Improved by 1 score	3,231	−12.92	8.03	−11	[−16.0 to −8.0]
Unchanged	3,621	−6.37	8.95	−6	[−11.0 to −1.0]
Worsened by 1 score	195	3.41	13.90	1	[−5.0 to +7.0]

Note:

a All observations (multiple observations per subject possible).

Abbreviations: IGA, Investigator Global Assessment; IQR, interquartile range.

Figure 1 Boxplot of the number of rosacea lesions by IGA score of “clear”/”minimal” (responders) vs “mild” to “severe” (nonresponders).

Note: The dashed horizontal line refers to the optimal separation threshold as determined by statistical discriminant analysis.
Abbreviation: IGA, Investigator Global Assessment.

Figure 2 Boxplot of the number of rosacea lesions by IGA score of “minimal” vs “mild.”

Note: The dashed horizontal line refers to the optimal separation threshold as determined by statistical discriminant analysis.
Abbreviation: IGA, Investigator Global Assessment.