Lower ratio of response with anakinra than other new RA drugs

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Jun 19, 2002

Lower ratio of response with anakinra than other new RA drugs

Stockholm, Sweden A review of clinical trial data with the newest drugs

used for rheumatoid arthritis suggests that both TNF inhibitors etanercept

(Enbrel®, Immunex & Wyeth) and infliximab (Remicade®, Centocor) and also

leflunomide (Arava®, Aventis) have comparable efficacy when used in

combination with methotrexate in incomplete responders. However, the IL-1

receptor antagonist anakinra (Kineret®, Amgen) showed a significantly lower

ratio of response as defined by the ACR50 response, according to a study

presented last week at the European Congress of Rheumatology.

The study compared the rate ratio of response (as defined by ACR50 responder

criteria) after 24-30 weeks of combination therapy with each new drug in RA

patients with active disease despite background MTX therapy. The data was

presented in a poster by Dr Marc C Hochberg (University of land School

of Medicine, Baltimore, MD).

Hochberg and colleagues had previously published a systematic review that

showed that in RA patients with an incomplete response on MTX, the addition

of cyclosporin, etanercept, infliximab, or leflunomide was associated with a

comparable rate of response according to ACR20 responder criteria after

24-30 weeks of combination therapy, as reported earlier by rheumawire. They

decided, however, that the use of ACR20 criteria, while able to

differentiate between active treatments and placebo, might not have been

sensitive enough to differentiate between more than one active agent.

Proportion of patients achieving ACR50 lower with anakinra

The researchers updated the data by including an MTX combination study

(990145) obtained from the Kineret Briefing Package (submitted to the FDA in

July of 2001). The review was ultimately based on the following double-blind

randomized controlled trials that used a step-up strategy with MTX as the

base therapy:

* Etanercept: Weinblatt, N Engl J Med 1999

* Infliximab: Maini, Lancet 1999

* Leflunomide: Kramer, Arthritis Rheum 2000

* Anakinra: Cohen, Arthritis Rheum 2001

Ratios for ACR50 and ACR70 response at 24-30 weeks were compared using

intent-to-treat populations. " You can't compare these trials head to head, "

remarked Hochberg. " That's why you have to compare rate ratios. "

The majority of the 1281 patients included in the analysis were white women

with a mean age of 55 and disease duration of 10 years. Overall 6.6% of 502

placebo-treated and 25% of 779 active-treated patients had an ACR50

response. The adjusted rate of an ACR50 response was 3.7.

The ratio of achieving an ACR50 response with anakinra was significantly

lower compared with the TNF-inhibitors or leflunomide (p <0.03). A similar

trend was also observed with the ACR70 response, though the analysis was

limited.

" The data suggest the proportion of RA patients with ACR50 or ACR70 response

is significantly lower with anakinra than with etanercept, infliximab, or

leflunomide, " indicate Hochberg and colleagues. " Nonetheless, these agents

are associated with a statistically comparable rate ratio of response and

NNTs as defined by ACR 50 and ACR70 outcomes. "

Higher NNT needed to see response with anakinra

" The data suggest that the number of patients you would need to treat in

order to see a clinically meaningful response would be higher using anakinra

than the other agents, " Hochberg told rheumawire. " So if you were running a

managed care system, anakinra would cost more money and you might start a

policy using something other than anakinra since it would cost less and you

could treat more patients. "

He stressed, however, that when comparing the placebo-controlled randomized

trials, it appears that the probability for a patient to get a response to

one or another of these drugs is " fairly similar. " It's only the use of more

rigorous definitions of response that indicate differences between the

drugs.

" Therefore in clinical practice, when the physician decides what drug to add

to the patient who has active disease despite being on methotrexate, they

have to discuss with the patient the route of administration of the drug,

the pattern of side effects the patient may have in response to each of

these drugs, and then the issue of cost and insurance coverage, and come to

a decision, " he concluded, adding that patients are " less keen " to use

anakinra because it requires daily injections.