Effectiveness, safety, and methotrexate dose-tapering pattern over two years of treatment with adalimumab and ≥12 mg/week methotrexate for early rheumatoid arthritis: Results of the HAWK postmarketing surveillance study in Japan

Figures & data

Table 1. Baseline demographics and patient characteristics (safety and effectiveness analysis set).

Baseline characteristic^a	Safety analysis set (n = 300)	Effectiveness analysis set (n = 292)
Sex, female	221 (73.7)	214 (73.3)
Age (years)
Mean (SD)	54.1 (13.9)	54.2 (13.9)
Weight^b (kg)
Mean (SD)	57.0 (12.0)	57.1 (12.0)
RA duration (months)
Mean (SD)	12.2 (6.2)	12.1 (6.2)
Comorbidities
Hepatic	29 (9.7)	28 (9.6)
Renal	3 (1.0)	3 (1.0)
Cardiovascular	39 (13.0)	38 (13.0)
Hematologic	10 (3.3)	10 (3.4)
Respiratory	14 (4.7)	13 (4.5)
Others	111 (37.0)	108 (37.0)
History of smoking	69 (23.0)	68 (23.3)
MTX dose
Mean (SD)	13.4 (1.7)	13.4 (1.8)
≥12.0 to <14.0 mg/week	172 (57.3)	168 (57.3)
≥14.0 to <16.0 mg/week	46 (15.3)	44 (15.0)
≥16.0 mg/week	82 (27.3)	80 (27.4)
Previous corticosteroid use	104 (34.7)	102 (34.9)
Steinbrocker stage
Stage I	164 (54.7)	159 (54.5)
Stage II	114 (38.0)	112 (38.4)
Stage III	17 (5.7)	17 (4.8)
Stage IV	5 (1.7)	4 (1.4)
Steinbrocker class
Class I	84 (28.0)	83 (28.4)
Class II	189 (63.0)	182 (62.3)
Class III	26 (8.7)	26 (8.9)
Class IV	1 (0.3)	1 (0.3)

MTX: methotrexate; RA: rheumatoid arthritis; SD: standard deviation.

^a Data are n (%) unless indicated otherwise.

^b For weight, n = 272 in safety analysis set; n = 265 in effectiveness analysis set.

Figure 1. Change in effectiveness measures over time. (a) DAS28-CRP. (b) DAS28-ESR. (c) CDAI. (d) SDAI. (e) HAQ-DI. (f) EQ-5D score. Data <1.0% are represented in the bars but are not labeled. CDAI: Clinical Disease Activity Index; DAS28-CRP: Disease Activity Score in 28 joints using C-reactive protein; DAS28-ESR: Disease Activity Score in 28 joints using erythrocyte sedimentation rate; EQ-5D: EuroQol-5 Dimensions; HAQ-DI: Health Assessment Questionnaire-Disability Index; SD: standard deviation; SDAI: Simplified Disease Activity Index.

Figure 2. Change in mTSS over time. mTSS: modified total Sharp score.

Figure 3. Rate of MTX tapering over time. MTX: methotrexate.

Figure 4. Change in effectiveness scores by MTX dose over time. (a) DAS28-CRP. (b) HAQ-DI. (c) mTSS. DAS28-CRP: Disease Activity Score in 28 joints using C-reactive protein; HAQ-DI: Health Assessment Questionnaire-Disability Index; mTSS: modified total Sharp score; MTX: methotrexate; SD: standard deviation.

Table 2. ADRs in patients with or without methotrexate dose tapering.

	Total N = 300		Methotrexate dose tapered n = 136		Methotrexate dose not tapered n = 164
	Non-serious ADRs	Serious ADRs	Non-serious ADRs	Serious ADRs	Non-serious ADRs	Serious ADRs
Overall, n (%)	74 (24.7)	26 (8.7)	51 (37.5)	13 (9.6)	23 (14.0)	13 (7.9)
Number of events	112	31	82	16	30	15
ADRs by SOC, n (%)
Infections and infestations	24 (8.0)	11 (3.7)	12 (8.8)	7 (5.2)	12 (7.3)	4 (2.4)
Investigations	19 (6.3)	1 (0.3)	17 (12.5)	0	2 (1.2)	1 (0.6)
Hepatobiliary disorders	12 (4.0)	0	12 (8.8)	0	0	0
Respiratory, thoracic, and mediastinal disorders	11 (3.7)	2 (0.7)	8 (5.9)	0	3 (1.8)	2 (1.2)
General disorders and administration site conditions	11 (3.7)	0	8 (5.9)	0	3 (1.8)	0
Gastrointestinal disorders	9 (3.0)	2 (0.7)	6 (4.4)	0	3 (1.8)	2 (1.2)
Skin and subcutaneous tissue disorders	9 (3.0)	1 (0.3)	5 (3.7)	1 (0.7)	4 (2.4)	0
Metabolism and nutrition disorders	2 (0.7)	0	2 (1.5)	0	0	0
Nervous system disorders	2 (0.7)	2 (0.7)	0	1 (0.7)	2 (1.2)	1 (0.6)
Musculoskeletal and connective tissue disorders	2 (0.7)	0	2 (1.5)	0	0	0
Renal and urinary disorders	1 (0.3)	3 (1.0)	1 (0.7)	2 (1.5)	0	1 (0.6)
Reproductive system and breast disorders	1 (0.3)	1 (0.3)	1 (0.7)	1 (0.7)	0	0
Neoplasms benign, malignant, and unspecified (including cysts and polyps)	0	4 (1.3)	0	2 (1.5)	0	2 (1.2)
Blood and lymphatic system disorders	0	2 (0.7)	0	1 (0.7)	0	1 (0.6)

ADR: adverse drug reaction; SOC: system organ class.