Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

Figures & data

Figure 1. Patient disposition. AEs were categorized according to whether they were considered related to study drug or not. AE adverse event, BID twice daily.

Table 1. Patient baseline demographics and disease characteristics.

Characteristic, Mean	Tofacitinib
	1 mg BID (n = 53)	3 mg BID (n = 53)	5 mg BID (n = 52)	10 mg BID (n = 53)	15 mg BID (n = 54)	Placebo (n = 52)
Age, years (SD)	53.3 (9.9)	52.8 (11.6)	52.6 (10.9)	54.7 (10.8)	53.6 (12.5)	53.3 (11.4)
Male, n (%)	11 (20.8)	6 (11.3)	8 (15.4)	9 (17.0)	10 (18.5)	9 (17.3)
Weight, kg (SD)	52.9 (9.4)	54.1 (10.2)	54.2 (6.6)	54.1 (10.0)	53.8 (9.9)	57.4 (11.7)
BMI, kg/m^2 (SD)	21.5 (3.2)	21.9 (3.8)	22.2 (2.9)	21.9 (3.9)	22.1 (3.2)	22.8 (3.8)
Duration of RA, years (range)	8.1 (0.5–39.0)	6.8 (0.6–28.0)	11.0 (0.4–34.0)	7.3 (0.5–45.0)	7.4 (0.5–38.3)	6.4 (0.5–38.0)
Tender joint count (SD)	13.55 (7.98)	17.26 (11.44)	18.58 (13.02)	17.13 (10.27)	17.35 (8.96)	15.10 (8.76)
Swollen joint count (SD)	11.30 (6.49)	14.64 (10.09)	15.31 (10.83)	13.77 (7.66)	14.48 (8.99)	11.96 (5.69)
PGA, mm (SD)	60.30 (22.40)	60.28 (19.92)	68.77 (22.28)	64.91 (21.25)	68.33 (18.79)	58.13 (25.27)
PtGA, mm (SD)	60.62 (22.19)	59.57 (18.83)	70.44 (19.85)	64.53 (22.51)	67.00 (19.97)	58.38 (21.83)
Patient pain assessment, mm (SD)	61.57 (17.37)	62.13 (18.09)	71.13 (17.54)	69.85 (15.21)	66.93 (17.60)	61.08 (16.79)
HAQ-DI (SD)	1.25 (0.59)	1.19 (0.64)	1.50 (0.69)	1.20 (0.65)	1.20 (0.69)	1.21 (0.69)
CRP, mg/L (SD)	30.21 (28.40)	25.65 (24.54)	35.61 (34.15)	26.88 (27.81)	27.37 (35.69)	24.01 (23.01)
DAS28-4(ESR) (SD)	6.04 (0.89)	6.08 (1.04)	6.41 (1.05)	6.06 (0.92)	6.20 (1.02)	5.83 (0.93)

BID twice daily, BMI body mass index, CRP C-reactive protein, DAS28-4(ESR) 28-joint disease activity score using erythrocyte sedimentation rate, HAQ-DI health assessment questionnaire-disability index, PGA physician global assessment, PtGA patient global assessment, RA rheumatoid arthritis, SD standard deviation.

Figure 2. Response rates for patients receiving tofacitinib monotherapy or placebo over time. (a) ACR20 response (± SE), FAS, LOCF. (b) DAS28-4(ESR) < 2.6 (remission), 2.6–3.2 (LDA), > 3.2–< 5.1 (MDA), and ≥ 5.1 (HDA), FAS, no imputation. (c) DAS28-4(ESR) < 2.6 (remission) (± SE), FAS, no imputation. (d) Mean HAQ-DI (± SE) change from baseline, FAS. *p < 0.05 versus placebo. ACR20 American College of Rheumatology 20% improvement criteria, BID twice daily, DAS28-4(ESR) 28-joint disease activity score using erythrocyte sedimentation rate, FAS full analysis set, HAQ-DI Health Assessment Questionnaire-Disability Index, HDA high disease activity, LDA low disease activity, LOCF last observation carried forward, MDA medium disease activity, SE standard error.

Table 2. Summary of safety data; all-causality TEAEs.

	Tofacitinib
	1 mg BID (n = 53)	3 mg BID (n = 53)	5 mg BID (n = 52)	10 mg BID (n = 53)	15 mg BID (n = 54)	Placebo (n = 52)
TEAEs, n	37	31	42	62	50	41
Patients with ≥ 1 TEAE, n (%)	21 (39.6)	23 (43.4)	29 (55.8)	32 (60.4)	28 (51.9)	23 (44.2)
Patients with ≥ 1 TESAE, n (%)	0	3 (5.7)	2 (3.8)	2 (3.8)	1 (1.9)	1 (1.9)
Discontinuations due to AEs, n (%)	0	1 (1.9)	2 (3.8)	3 (5.7)	0	2 (3.8)
Deaths	0	0	0	0	0	0

AE adverse event, BID twice daily, TEAE treatment-emergent adverse event, TESAE treatment-emergent serious adverse event.

Table 3. Most common all-causality treatment-emergent AEs occurring in ≥ 2% patients in any of the treatment groups.

AE, n (%)*	Tofacitinib
	1 mg BID (n = 53)	3 mg BID (n = 53)	5 mg BID (n = 52)	10 mg BID (n = 53)	15 mg BID (n = 54)	Placebo (n = 52)
Nasopharyngitis	6 (11.3)	4 (7.5)	6 (11.5)	3 (5.7)	8 (14.8)	6 (11.5)
Hyperlipidemia	1 (1.9)	0	2 (3.8)	6 (11.3)	3 (5.6)	0
Headache	1 (1.9)	3 (5.7)	2 (3.8)	1 (1.9)	0	1 (1.9)
LDL-C increased	0	1 (1.9)	0	1 (1.9)	6 (11.1)	0
ALT increased	0	2 (3.8)	0	1 (1.9)	1 (1.9)	3 (5.8)
Constipation	1 (1.9)	0	1 (1.9)	0	3 (5.6)	2 (3.8)
Pharyngitis	0	0	0	3 (5.7)	2 (3.7)	1 (1.9)
Stomatitis	1 (1.9)	1 (1.9)	2 (3.8)	1 (1.9)	0	1 (1.9)
Abdominal discomfort	2 (3.8)	1 (1.9)	0	1 (1.9)	0	1 (1.9)
AST increased	0	1 (1.9)	0	1 (1.9)	0	3 (5.8)
Blood cholesterol increased	0	1 (1.9)	1 (1.9)	1 (1.9)	2 (3.7)	0
Fall	3 (5.7)	0	1 (1.9)	1 (1.9)	0	0
Herpes zoster	0	0	1 (1.9)	3 (5.7)	1 (1.9)	0
Hypercholesterolemia	0	2 (3.8)	0	3 (5.7)	0	0
Bronchitis	1 (1.9)	1 (1.9)	0	2 (3.8)	0	0
Contusion	2 (3.8)	1 (1.9)	0	0	1 (1.9)	0
Dental caries	0	0	2 (3.8)	1 (1.9)	0	1 (1.9)
Gingivitis	0	1 (1.9)	0	0	2 (3.7)	1 (1.9)
Hypertension	0	0	3 (5.8)	1 (1.9)	0	0
Upper respiratory tract infection	0	0	1 (1.9)	3 (5.7)	0	0
Diarrhea	1 (1.9)	0	0	0	0	2 (3.8)
Gastritis	0	1 (1.9)	0	0	2 (3.7)	0
RA	0	0	0	0	0	2 (3.8)
Upper respiratory tract inflammation	0	0	0	0	0	2 (3.8)

AE adverse event, ALT alanine transaminase, AST aspartate transaminase, BID twice daily, LDL-C low-density lipoprotein cholesterol.

*Preferred terms according to Medical Dictionary for Regulatory Activities version 13.0.

Table 4. Mean changes in laboratory parameters from baseline at week 12.

Parameter Mean change	Tofacitinib
	1 mg BID	3 mg BID	5 mg BID	10 mg BID	15 mg BID	Placebo
	n = 51	n = 49	n = 50	n = 49	n = 52	n = 48
Neutrophils, × 10^3/mm^3	0.06	–0.98^‡	–1.44^‡§	–2.10^‡	–1.66^‡	0.47
HDL-C, mg/dL	5.04^†	10.81^‡	17.73^‡	21.94^‡	21.11^‡	–0.94
LDL-C, mg/dL	3.21	11.77^†	16.43^‡	21.45^‡	24.69^‡	–0.24
TC, mg/dL	11.52^†	25.44^‡	35.83^‡	50.35^‡	51.31^‡	–0.96
Hemoglobin, g/dL	0.15*	0.25^†	0.48^‡§	0.56^‡	0.19*	–0.15
Serum creatinine, mg/dL	0.01	0.02*	0.04^‡	0.05^‡	0.06^‡	–0.01

No. of patients (%)	n = 53	n = 53	n = 52	n = 53	n = 54	n = 52
Lymphocytes, < 1000/mm^3	11 (20.8)	6 (11.3)	11 (21.2)	12 (22.6)	16 (29.6)	18 (34.6)
Lymphocytes, < 500/mm^3	0	0	0	3 (5.7)	0	0
Neutrophils, < 500/mm^3	0	0	0	0	0	0
Hemoglobin, decrease of 2–3 g/dL from baseline or hemoglobin < 8 g/dL	0	0	0	0	0	0
AST or ALT > 3 × ULN	1 (1.9)	1 (1.9)	0	0	1 (1.9)	2 (3.8)

ALT alanine transaminase, AST aspartate transaminase, BID twice daily, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, TC total cholesterol, ULN upper limit of normal.

*p < 0.05; ^†p < 0.01; ^‡p < 0.001 versus placebo. ^§n = 49.