El etanercept es eficaz y bien tolerado en pacientes chinos con espondilitis anquilosante: 6 semanas controlado con placebo, seguido de 6 semanas de tratamiento abierto

BACKGROUND:

This was a registration study of etanercept 50 mg (ETN) once weekly (QW) in pts with ankylosing spondylitis (AS).

OBJECTIVES:

To evaluate the efficacy and safety of ETN in a 6-wk double blind placebo (PBO)-controlled study in adult pts with AS followed by a 6-wk open-label evaluation of safety.

METHODS:

Efficacy and safety were evaluated in a 6-wk randomized, double-blind, PBO-controlled study (Part A), followed by a 6-wk open-label safety phase (Part B). Pts receiving stable hydrochloroquine, sulfasalazine, or methotrexate at screening could continue taking these agents during the study. During part A, pts were randomly assigned ETN or PBO, subcutaneously; during Part B all pts received ETN. The primary endpoint of the study was percentage of pts achieving a 20% improvement by the assessment in ankylosing spondylitis (ASAS 20) criteria at Wk 6. Secondary endpoints included ASAS 40, ASAS 5/6, and partial remission. Safety evaluations included adverse events (AEs) and routine laboratory monitoring. The modified intent-to-treat population, which includes all pts who received ≥1 dose of study drug, was used for both efficacy and safety analyses. Binary endpoints were analyzed using the Fisher exact test; continuous endpoints were analyzed using analysis of covariance with treatment as a factor and baseline value as covariate.

RESULTS:

Of 152 pts enrolled, 74 were randomly assigned ETN 50 mg QW and 78 PBO. 150 pts completed Part A and continued into Part B; 147 completed Part B. Baseline demographics and disease characteristics were similar between the groups. The primary endpoint, ASAS 20 at wk 6, was achieved by 86.5% pts receiving ETN v. 29.5% receiving PBO (p<.001). A significant difference between the 2 groups in the percentage of ASAS 20 responders and most other endpoints was seen as early as 2 weeks (p<.001). At wk 6, ASAS 40 and ASAS 5/6 responses were achieved by 63.5% and 71.4%, respectively, of pts receiving ETN v. 16.7% (p<.001 for both) of pts receiving PBO. At the end of 6 wks, more pts receiving ETN (16.2%) achieved partial remission v. those receiving PBO (5.1%; p<.05). For pts who started receiving ETN during Part B, a response pattern similar to that seen in pts who received ETN during the 6-wk double-blind period (PartA); at wk 12, 93.2% of pts from the original ETN group and 92.2% from the original PBO group were ASAS 20 responders. AEs were reported by 24.3% of pts receiving ETN and 12.8% receiving PBO (p=.09) during Part A; none of the events were considered SAEs and there were no AE-related discontinuations. The most common AEs(≥3%) reported were abnormal hepatic enzyme levels, upper respiratory infection (URI) and injection site reaction (ISR). Abnormal hepatic enzyme levels (p<.01) and ISR (p not significant [NS]) occurred more often with ETN; URI occurred more often with PBO (p NS). Hepatic enzyme levels were <1.5xULN in the majority of pts; ∼50% occurred only once. During Part B, 20.7% of pts reported ≥1 AE; none were considered serious.

CONCLUSIONS:

The response to etanercept was rapid, highly effective and well tolerated in Chinese patients with AS.