Enbrel and Kineret combo in RA: no added benefit

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Rheumawire

May 31, 2004

Etanercept and anakinra combo in RA: no added benefit

New York, NY - Promising animal studies suggesting that a combination of

a tumor necrosis factor (TNF) blocker with an interleukin-1 (IL-1)

antagonist may act synergistically have not been borne out in the

clinic.

A trial in 244 patients with rheumatoid arthritis (RA) showed no added

benefit and an increased risk of infection with the combination of

etanercept (Enbrel®; Amgen/Wyeth) and anakinra (Kineret®, Amgen)

compared with the use of etanercept alone. The results are reported by

Dr Mark Genovese (Stanford University, Palo Alto, CA) and colleagues in

the May 2004 issue of Arthritis & Rheumatism [1].

Patients participating in this study had active RA despite methotrexate

treatment and had not previously received any biologic therapy. They

were randomized to receive:

Etanercept alone at a full dosage of 25 mg twice weekly (n=80).

Etanercept 25 mg twice weekly plus anakinra 100 mg/day (n=81).

Half-dose etanercept 25 mg once weekly plus anakinra 100 mg/day

(n=81).

After 6 months, an ACR50 response was seen in 31% of patients treated

with full-dose etanercept plus anakinra, compared with 41% of those who

received etanercept only (p=0.914). No serious infections developed in

patients taking etanercept alone, the researchers note. By contrast,

3.7% to 7.4% of patients taking either regimen of combination therapy

developed serious infections, including pneumonia, cellulites, herpes

zoster, pneumonitis, and pyelonephritis. In addition, injection-site

reactions and neutropenia increased with the combined regimen.

" These [results] are disappointing in the sense that we had hoped that

the combination would result in synergistic, if not added, benefits to

the patient, " Genovese commented to rheumawire. " We had also hoped that

the success that had been seen in the animal models of arthritis would

translate into real-world benefits for our patients. "

Exactly why the combination did not work is unclear, but 1 theory is

that the degree of overlap between IL-1 and TNF may not leave much room

for improvement beyond what is seen with effective TNF blockade alone.

" At this point the combination of anti-TNF therapy and anti-IL-1 therapy

does not appear to be useful in the majority of patients and is

accompanied by an increased risk of infection, " he says.

But all is not lost. " The failure of this combination to demonstrate

additive or synergistic [effects] by no means limits or reduces the

likelihood that other combination biologic agents may and probably will

prove useful in the future, " he tells rheumawire.

Mann

Source

1. Genovese MC, Cohen S, Moreland L, et al. Combination therapy with

etanercept and anakinra in the treatment of patients with rheumatoid

arthritis who have been treated unsuccessfully with methotrexate.

Arthritis Rheum 2004 May; 50(5):1412-9.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org