Better clinical responses seen early with the loading dose of certolizumab pegol are maintained until one year

Background Certolizumab pegol (CZP) has demonstrated rapid and sustained improvements in disease activity in Japanese patients (pts) with active rheumatoid arthritis (RA), both with methotrexate (J-RAPID; NCT00791999) and with or without DMARDs other than methotrexate (HIKARI; NCT00791921) in placebo-controlled double-blind (DB) randomized trials.1,2 Although previous analysis suggested that the loading dose (LD) of CZP (400mg at Weeks (Wks) 0, 2 and 4) improves the clinical response of CZP for the first 24 wks3, the impact of the initial LD on the long-term outcomes remains unknown. Objectives To compare the safety, efficacy and immunogenicity 1 year (yr) after initiation of CZP with and without the LD. Methods Data from the Japanese clinical trials1,2 and the respective open-label extensions (OLEs) (

J-RAPID OLE:

NCT00851318;

HIKARI OLE:

NCT00850343)4,5 were used for this analysis. Pts randomized to receive CZP 200mg every 2 wks (Q2W) with the LD were defined as LD groups (

J-RAPID:

n=82;

HIKARI:

n=116), whereas pts randomized to receive placebo in the DB trials who entered the respective OLEs and initiated CZP 200mg Q2W without LD were defined as No-LD groups (

J-RAPID:

n=61;

HIKARI:

n=99). The ACR response rates, achievement of DAS28 LDA, safety assessments, plasma CZP levels and rates of anti-CZP antibodies (Abs) were analyzed up to 1yr after initiating CZP. DB baseline for the LD groups and at OLE entry for the No-LD groups were used as the baselines. Results The ACR20/50/70 responses of the LD vs No-LD groups in J-RAPID were 74.4%/62.2%/32.9% vs 76.8%/60.7%/26.8%, and in HIKARI were 69.0%/50.9%/31.9% vs 62.1%/43.2%/23.2%, respectively, at 1yr (Figure). The LD groups had higher proportion of pts in DAS28 LDA (

J-RAPID:

48.8% vs 42.6%;

HIKARI:

42.2% vs 26.3%). Frequency of anti-CZP Abs was lower in the LD groups than in the No-LD groups (

J-RAPID:

n=2/82 [2.4%] vs n=4/61 [6.6%];

HIKARI:

n=30/116 [25.9%] vs n=32/99 [32.3%]). Pts who developed anti-CZP Abs had lower plasma CZP levels and lower clinical responses than Ab-negative pts. Safety profiles were similar between the groups. (Figure presented) Conclusions While this post-hoc analysis has limitations including the comparison of DB vs OLE data, the results suggest that the benefits potentially due to the initial loading dose are sustained until at least 1yr without additional risk of adverse events.