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In all five Phase III studies, patients treated with ACTEMRA 8mg/kg had statistically significant higher American College of Rheumatology (ACR) 20, 50 and 70 response rates at six months compared with control (Table 1). In AMBITION, superiority of ACTEMRA 8mg/kg was demonstrated against the active comparator methotrexate (MTX).

The treatment effect was similar in patients independent of rheumatoid factor status, age, gender, race, number of prior treatments or disease status. Time to onset was rapid (as early as Week 2) and the magnitude of response continued to improve with duration of treatment. Continued durable responses were seen for over 24 months in the ongoing open-label extension studies (OPTION, TOWARD, AMBITION and RADIATE).  

In patients treated with ACTEMRA 8mg/kg, significant improvements were noted on all individual components of the ACR response including: tender and swollen joint counts; patient and physician global assessment; disability index scores; pain assessment and C-reactive protein (CRP), compared with patients receiving placebo plus MTX or other disease modifying anti-rheumatic drugs (DMARDs) in all studies.

Patients in all five studies had a mean Disease Activity Score (DAS28) of 6.5-6.8 at baseline. Significant reduction in DAS28 from baseline (mean improvement) of 3.1-3.4 was observed in ACTEMRA-treated patients compared to control patients (1.3-2.1). The proportion of patients achieving a DAS28 clinical remission (DAS28 <2.6) was significantly higher in patients receiving ACTEMRA (28-34%) compared to 1-12% of control patients at 24 weeks. In LITHE, 47% of patients achieved a DAS28 <2.6 at 52 weeks compared with 33% of patients at Week 24.

In a pooled analysis of OPTION, TOWARD and LITHE, the proportion of patients achieving an ACR20, 50 and 70 response was significantly higher (59% vs. 50%, 37% vs. 27%, 18% vs. 11%, respectively) in the ACTEMRA 8mg/kg plus DMARD vs. the ACTEMRA 4mg/kg plus DMARD group (p<0.03). Similarly, the proportion of patients achieving a DAS28 remission (DAS28 <2.6) was significantly higher (31% vs. 16% respectively) in patients receiving ACTEMRA 8mg/kg plus DMARD than in patients receiving ACTEMRA 4mg/kg plus DMARD (p<0.0001).

Table 1. ACR responses in placebo-/MTX-/DMARDs-controlled studies (% patients)

	Study I AMBITION		Study II LITHE		Study III OPTION		Study IV TOWARD		Study V RADIATE
Week	TCZ 8mg/kg	MTX	TCZ 8mg/kg MTX	PBO MTX	TCZ 8mg/kg MTX	PBO MTX	TCZ 8mg/kg DMARD	PBO DMARD	TCZ 8mg/kg MTX	PBO MTX
	n = 286	n = 284	n = 398	n = 393	n = 205	n = 204	n = 803	n = 413	n = 170	n = 158
ACR 20
24	70%***	53%	56%***	27%	59%***	27%	61%***	25%	50%***	10%
52			56%***	25%
ACR 50
24	44%***	34%	32%***	10%	44%***	11%	38%***	9%	29%***	4%
52
ACR 70
24	28%***	15%	13%***	2%	22%***	2%	21%***	3%	12%**	1%
52			20%***	4%

TCZ - Tocilizumab
MTX - Methotrexate
PBO - Placebo
DMARD - Disease modifying anti-rheumatic drug
* - p< 0.05, TCZ vs. PBO MTX/DMARD
** - p< 0.01, TCZ vs. PBO MTX/DMARD
*** - p< 0.0001, TCZ vs. PBO MTX/DMARD

Radiographic response

In LITHE, in patients with an inadequate response to MTX, inhibition of structural joint damage was assessed radiographically and expressed as change in modified Sharp score and its components, the erosion score and joint space narrowing score. Inhibition of joint structural damage was shown with significantly less radiographic progression in patients receiving ACTEMRA compared with control (Table 2).

Table 2. Radiographic mean changes over 52 weeks in LITHE

	PBO MTX ( TCZ from week 24) n = 393	TCZ 8mg/kg MTX n = 398
Total Sharp-Genant score	1.13	0.29*
Erosion score	0.71	0.17*
JSN score	0.42	0.12**

PBO - Placebo
MTX - Methotrexate
TCZ - Tocilizumab
JSN - Joint space narrowing
* - p≤ 0.0001, TCZ vs. PBO MTX
** p< 0.005, TCZ vs. PBO MTX

Health-related and quality of life outcomes

ACTEMRA-treated patients reported an improvement in all patient-reported outcomes (Health Assessment Questionnaire Disability Index - [HAQ-DI]), Short Form-36 and Functional Assessment of Chronic Illness Therapy questionnaires. Statistically significant improvements in HAQ-DI scores were observed in patients treated with ACTEMRA compared with patients treated with DMARDs.

Haemoglobin levels

Statistically significant improvements in haemoglobin levels were observed with ACTEMRA compared with DMARDs (p<0.0001) at Week 24. Mean haemoglobin levels increased by Week 2 and remained within normal range through to Week 24.

Reference:
Actemra Product Information (HK). Current at August 2010