Intra-articular etanercept safe, effective in RA patients

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Jun 13, 2002

Intra-articular etanercept safe, effective in RA patients

Stockholm, Sweden Etanercept (Enbrel®, Wyeth) injected directly into the

joints of rheumatoid arthritis (RA) patients with particularly active joints

is both safe and efficacious, and could be used as an alternative to

intra-articular steroid injections, according to a study presented today at

the European Congress of Rheumatology (EULAR).

Because of the adverse events associated with the injected steroids used in

active synovitis, alternative medications are needed, according to lead

researcher Dr Henning Bliddal ( Institute, Frederiksberg Hospital,

Copenhagen, Denmark). He and colleagues looked at anti-TNF therapy and chose

etanercept since it has been used successfully systemically, as well as

intra-articularly in animals.

The study, which received support from Wyeth, was randomized, controlled,

double-blind (dosage) and observer blinded. Patients with active synovitis

of at least 2 joints were eligible for an etanercept injection if they had

been considered for an intra-articular steroid injection. The mean age of

patients was 58 and 16 were seropositive. Two joints were chosen in each

patient ‹ one as a control and the other for injection.

Hand swelling only adverse event

In phase I, patients were randomized to etanercept doses of 2, 4, and 8 mg.

Due to lack of effect, the 8-mg dose was used exclusively in the second part

of the study. Observers evaluated the joints clinically and determined

sedimentation rate and C-reactive protein. A total of 26 patients were

injected (16 wrists, 6 MCP, PIP, DIP, or MTP joints, 2 elbows, and 2

ankles).

The skin and tissue outside the synovium were anesthetized prior to the

injection, and an aspiration of the joint was carried out. The position and

verification of injections were guided by ultrasound, given that " blind "

injections miss their target 10-50% of the time, noted Bliddal. Ultrasound

is a very helpful tool in ensuring correct needle placement in the joint

space, he said, and the procedure can be tested with air prior to the actual

drug injection.

Following the injection, 7 patients were examined clinically and with

ultrasound the first 3 days, and then all were seen weekly, and then monthly

for 3 months. Only 1 patient (who received 4 mg of etanercept to the wrist)

experienced an adverse event ‹ swelling on the back of the hand that

resolved in 2 days. Other than a temporary local soreness following the

administration of the needle, no other adverse events were recorded.

Doppler activity decreased following injection

Following the etanercept injection, the visual analog score (VAS) normalized

to the level at onset (defined as 1.0), decreased after 1 week in 23 of 25,

and decreased at 1 month in 18 of 25.

Doppler ultrasound was used as the final end point, specifically the

fraction of colored pixels outlined in the region of interest in the joint.

" The pixel fraction did drop [in the patients injected with etanercept], but

not dramatically, " said Bliddal; 18 of 25 saw a drop after 1 week and 21 of

25 after 1 month. " In the control joints, no change was seen. "

Several joints went into long-lasting remission, and in 1 DIP after 2 mg and

1 wrist after 4 mg Doppler activity was extinguished altogether. Only 1

patient reported relief in joints other than the wrist, which was injected

with 8 mg etanercept. A more localized effect was also seen within the ankle

and elbow joints. MRI was also used, though of the 21 who had MRIs at

baseline, only 9 were willing to repeat the procedure. He and colleagues

looked at the thickness of the worst part of the infected joint, and saw a

decrease in the synovial tissue.

Bliddal concluded that the intra-articular injection of etanercept is safe

and effective, resulting in a reduction in the blood supply and the size of

the synovium. He said that intra-articular etanercept could be considered an

alternative to intra-articular steroids, and suggested that higher doses be

considered for larger joints.