ABSTRACT
OBJECTIVE: To compare adalimumab versus etanercept in patients with active rheumatoid arthritis (RA) to test the hypothesis that adalimumab was not inferior to etanercept in terms of drug continuation by a margin of 15% after 52 weeks of treatment. DESIGN: Pragmatic, randomised, parallel group, multicentre, unblinded and non-inferiority trial. Randomisation stratified by baseline use of methotrexate. PARTICIPANTS: 125 adults with active RA despite treatment with two disease-modifying drugs (DMARDs), including methotrexate randomised (1 : 1) to adalimumab 40 mg alternate weeks or etanercept 50 mg weekly, added to existing medication. MEASUREMENTS: The primary outcome was proportion of patients continuing treatment after 52 weeks. Secondary outcomes included: disease activity score using 28 joints (DAS28), treatment satisfaction (TSQM V.2), health status (Euroqol-5D), drug toxicity and persistence with therapy after 2 years. RESULTS: Persistence with therapy was 65% for adalimumab versus 56.7% for etanercept (one-sided 95% CI for proportion still taking adalimumab minus proportion on etanercept ≥-7.9%); demonstrating non-inferiority at the 15% margin. After 2 years these figures were: adalimumab 58.3% and etanecept 43.3% (CI ≥-1.7%). The proportion of good, moderate and non-responders based on DAS28-C reactive protein, after 52 weeks, were 26.3%, 33.3% and 40.4%, respectively, for adalimumab versus 16.7%, 31.7% and 51.7%, respectively, for etanercept (p=0.158). Baseline median EQ-5D scores improved from 0.52 to 0.69 for adalimumab and from 0.52 to 0.64 for etanercept (p=0.046) after 52 weeks. Global satisfaction, effectiveness, side effects and convenience scores based on the TSQM were similar for both drugs. Fourteen serious adverse events occurred including two deaths from myocardial infarction, one patient with ovarian cancer and one with acute myeloid leukaemia. CONCLUSIONS: Clinicians choosing a first tumour necrosis factor inhibitor for active RA, despite trying two DMARDs including methotrexate, may choose either adalimumab or etanercept in the knowledge that these drugs are similarly effective. CLINICAL TRIAL REGISTRATION NUMBER: EU Clinical Trials Register 2006-006275-21/GB.
ABSTRACT
OBJECTIVES: To compare the effect of acupuncture (manual and electroacupuncture) with that of a non-penetrating sham ('placebo' needle) in patients with osteoarthritic knee pain and disability who are blind to the treatment allocation. METHODS: Acupuncture naïve patients with symptomatic and radiological evidence of osteoarthritis of the knee were randomly allocated to a course of either acupuncture or non-penetrating sham acupuncture using a sheathed 'placebo' needle system. Acupuncture points for pain and stiffness were selected according to acupuncture theory for treating Bi syndrome. Both manual and electrical stimulation were used. Response was assessed using the WOMAC index for osteoarthritis of the knee, self reported pain scale, the EuroQol score and plasma beta-endorphin. The effectiveness of blinding was assessed. RESULTS: There were 34 patients in each group. The primary end point was the change in WOMAC pain score after the course of treatment. Comparison between the two treatment groups found a significantly greater improvement with acupuncture (mean difference 60, 95% CI 5 to 116, P= 0.035) than with sham. Within the acupuncture group there was a significant improvement in pain (baseline 294, mean change 95, 95% CI 60 to 130, P<0.001) which was not seen by those who had sham acupuncture (baseline 261, mean change 35, 95% CI -10 to 80, P=0.12). Similar effects within group, but not between groups, were seen with the secondary end points of WOMAC stiffness, WOMAC function, and self reported pain. One month after treatment the between group pain difference had been lost (mean difference 46; 95% CI -9 to 100, P=0.10) although the acupuncture group was still benefiting compared to baseline (mean difference 59; 95% CI 16 to 102, P=0.009). The EuroQol score, a generic measure of health related quality of life, was not altered by the treatments. A minority of patients correctly guessed their treatment group (41% in the acupuncture group and 44% in the control group). Plasma beta-endorphin levels were not affected by either treatment. CONCLUSIONS: Acupuncture gives symptomatic improvement for patients with osteoarthritis of the knee, and is significantly superior to non-penetrating sham acupuncture. The study did not confirm earlier reports of release of plasma beta-endorphin during acupuncture.
