Pooled safety analysis of diclofenac sodium topical solution 1.5% (w/w) in the treatment of osteoarthritis in patients aged 75 years or older

Figures & data

Table 1 Baseline demographics of patients

Parameter	Treatment group			P valuea (versus placebo)
	TDiclo (n = 138)	Placebo (n = 39)	Control (n = 103)	TDiclo	Control
Age (years)
Mean (SD)	78.4 (2.8)	77.9 (2.8)	78.1 (2.6)	0.427	0.719
Minimum, maximum	75, 85	75, 84	75, 85
Gender, n (%)
Male	64 (46.4)	19 (48.7)	34 (33.0)	0.796	0.084
Female	74 (53.6)	20 (51.3)	69 (67.0)
Race, n (%)
White	131 (94.9)	36 (92.3)	95 (92.2)	0.577	0.915
Black	3 (2.2)	1 (2.6)	4 (3.9)
Hispanic	1 (0.7)	1 (2.6)	1 (1.0)
Asian	2 (1.4)	1 (2.6)	3 (2.9)
Other	1 (0.7)	0 (0.0)	0 (0.0)

Note:

a P values were derived from Chi-square test or Fisher’s Exact test for categorical parameters or from analysis of variance with a main treatment effect for continuous parameters.

Abbreviations: SD, standard deviation; TDiclo, diclofenac sodium topical solution.

Table 2 Clinical characteristics of patients

Parameter	Treatment group			P valuea (versus placebo)
	TDiclo (n = 138)	Placebo (n = 39)	Control (n = 103)	TDiclo	Control
Body mass index (kg/m^2)b
Mean (SD)	29.7 (5.2)	27.2 (5.4)	28.0 (5.0)	0.077	0.575
Minimum, maximum	21, 45	22, 43	22, 44
Hypertension, n (%)
Yes	84 (60.9)	15 (38.5)	63 (61.2)	0.013	0.015
No	54 (39.1)	24 (61.5)	40 (38.8)
Diastolic blood pressurec (mmHg)
Mean (SD)	77.7 (9.4)	75.3 (10.2)	76.6 (8.5)	0.161	0.436
Minimum, maximum	50, 114	50, 94	52, 96
Systolic blood pressurec (mmHg)
Mean (SD)	137.9 (15.6)	133.1 (17.3)	138.7 (17.8)	0.101	0.094
Minimum, maximum	100, 182	108, 180	98, 210

Notes:

a P values were derived from Chi-square test or Fisher’s Exact test for categorical parameters or from an analysis of variance with a main treatment effect for continuous parameters;

b weight or height data were not available for 95 patients (68.8%) in the TDiclo group, 15 patients (38.5%) in the placebo group, and 55 patients (53.4%) in the control group;

c blood pressure measurements were missing from one patient (2.56%) in the placebo group.

Abbreviations: SD, standard deviation; TDiclo, diclofenac sodium topical solution.

Table 3 Incidence of treatment-emergent skin or subcutaneous tissue and gastrointestinal adverse events affecting ≥1% of patients

Adverse event, n (%)a	Treatment group			P valueb (versus placebo)
	TDiclo (n = 138)	Placebo (n = 39)	Control (n = 103)	TDiclo	Control
Skin/subcutaneous tissue	61 (44.2)	3 (7.7)	31 (30.1)	<0.0001	0.0042
Dry skin	50 (36.2)	1 (2.6)	19 (18.4)	<0.0001	0.014
Erythema	8 (5.8)	2 (5.1)	3 (2.9)	>0.999	0.615
Contact dermatitis	7 (5.1)	0 (0.0)	0 (0.0)	0.350	–
Pruritus	4 (2.9)	1 (2.6)	6 (5.8)	>0.999	0.674
Bullous dermatitis	3 (2.2)	0 (0.0)	0 (0.0)	>0.999	–
Rash	3 (2.2)	0 (0.0)	3 (2.9)	>0.999	0.562
Gastrointestinal	24 (17.4)	7 (17.9)	9 (8.7)	0.936	0.121
Constipation	5 (3.6)	0 (0.0)	2 (1.9)	0.588	>0.999
Diarrhea	5 (3.6)	2 (5.1)	1 (1.0)	0.650	0.183
Nausea	5 (3.6)	2 (5.1)	3 (2.9)	0.650	0.615
Abdominal pain, upper	4 (2.9)	0 (0.0)	0 (0.0)	0.577	–
Dyspepsia	4 (2.9)	0 (0.0)	1 (1.0)	0.577	>0.999
Abdominal distension	3 (2.2)	0 (0.0)	1 (1.0)	>0.999	>0.999
Abdominal pain	1 (0.7)	1 (2.6)	2 (1.9)	0.393	>0.999

Notes:

a Patients experiencing multiple episodes of a given adverse event were counted once within each row;

b P values were derived from Chi-square test or Fisher’s Exact test. Cases in which statistical testing was not possible due to the absence of adverse events are indicated by (–).

Abbreviation: TDiclo, diclofenac sodium topical solution.

Figure 1 Incidence of dry skin among patients in the TDiclo, placebo, and control groups.

Note: Significant differences between groups are indicated.
Abbreviation: TDiclo, diclofenac sodium topical solution.

Table 4 Overall incidence of treatment-emergent skin or subcutaneous tissue and gastrointestinal adverse events that resulted in study discontinuation in ≥1% of patients

Adverse event, n (%)a	Treatment group			P valueb (versus placebo)
	TDiclo (n = 138)	Placebo (n = 39)	Control (n = 103)	TDiclo	Control
Skin/subcutaneous tissue	10 (7.2)	0 (0.0)	1 (1.0)	0.120	>0.999
Dry skin	4 (2.9)	0 (0.0)	0 (0.0)	0.577	–
Erythema	4 (2.9)	0 (0.0)	0 (0.0)	0.577	–
Contact dermatitis	3 (2.2)	0 (0.0)	0 (0.0)	>0.999	–
Pruritus	3 (2.2)	0 (0.0)	1 (1.0)	>0.999	>0.999
Gastrointestinal	6 (4.3)	2 (5.1)	2 (1.9)	>0.999	0.303
Abdominal pain, upper	3 (2.2)	0 (0.0)	0 (0.0)	>0.999	–
Nausea	2 (1.4)	2 (5.1)	0 (0.0)	0.211	0.074

Notes:

a Patients experiencing multiple episodes of a given adverse event were counted once within each row;

b P values were derived from a Chi-square test or Fisher’s Exact test. Cases in which statistical testing was not possible due to the absence of adverse events are indicated by (–).

Abbreviation: TDiclo, diclofenac sodium topical solution.

Figure 2 Incidence of application site-related adverse events among patients in the TDiclo, placebo, and control groups.

Abbreviation: TDiclo, diclofenac sodium topical solution.

Table 5 Changes in blood pressure and key laboratory measurements from baseline to the final visit

Measurementa	Treatment group			P valueb (versus placebo)
	TDiclo (n = 138)	Placebo (n = 39)	Control (n = 103)	TDiclo	Control
Δ Diastolic blood pressure (mmHg)	(n = 125)	(n = 28)	(n = 86)
Mean (SD)	−1.13 (10.24)	−3.11 (7.81)	0.24 (8.88)	0.338	0.077
Minimum, maximum	−30.0, 25.0	−24.0, 11.0	−38.0, 26.0
Δ Systolic blood pressure (mmHg)	(n = 125)	(n = 28)	(n = 86)
Mean (SD)	−3.61 (15.16)	−0.32 (16.14)	−2.37 (19.27)	0.307	0.613
Minimum, maximum	−44.0, 40.0	−32.0, 30.0	−52.0, 50.0
Δ Alanine aminotransferase (IU/L)	(n = 76)	(n = 27)	(n = 31)
Mean (SD)	2.61 (12.61)	−0.26 (3.93)	1.87 (13.67)	0.250	0.438
Minimum, maximum	−18.0, 96.0	−8.0, 9.0	−10.0, 64.0
Δ Aspartate aminotransferase (IU/L)	(n = 76)	(n = 27)	(n = 31)
Mean (SD)	2.34 (8.97)	0.19 (3.13)	2.94 (14.30)	0.225	0.332
Minimum, maximum	−16.0, 53.0	−7.0, 6.0	−7.0, 72.0
Δ Creatinine (μmol/L)	(n = 76)	(n = 25)	(n = 31)
Mean (SD)	0.53 (11.43)	2.60 (13.67)	3.81 (11.67)	0.456	0.723
Minimum, maximum	−28.0, 33.0	−25.0, 53.0	−32.0, 29.0
Δ Gamma-glutamyltransferase (IU/L)	(n = 62)	(n = 16)	(n = 15)
Mean (SD)	5.23 (27.04)	0.50 (6.69)	−2.87 (7.03)	0.492	0.182
Minimum, maximum	−29.0, 182.0	−12.0, 15.0	−19.0, 6.0
Δ Hemoglobin (g/L)	(n = 75)	(n = 27)	(n = 31)
Mean (SD)	−0.72 (7.52)	2.04 (6.48)	−0.84 (7.53)	0.094	0.127
Minimum, maximum	−19.0, 32.0	−12.0, 19.0	−14.0, 15.0

Notes:

a Values shown represent the change in each measurement from baseline to the final visit. First or final visit blood pressure measurements were missing for 13 patients (9.4%) in the TDiclo group, 11 patients (28.2%) in the placebo group, and 17 patients (16.5%) in the control group. Laboratory data were available for four of the seven pooled trials (80 patients in the TDiclo group, 31 patients in the placebo group, and 34 patients in the control group). Of those trials for which laboratory data were available, baseline or final visit data were missing for 4–18 patients (5.0%–22.5%) in the TDiclo group, 4–15 patients (12.9%–48.4%) in the placebo group, and 3–19 patients (8.8%–55.9%) in the control group. Adjusted sample sizes are listed for each measurement in the column headings;

b P values were derived using analysis of variance (with a main treatment effect).

Abbreviations: SD, standard deviation; TDiclo, diclofenac sodium topical solution.