Anakinra rarely works in RA if TNF inhibitors have already failed

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Anakinra rarely works in RA if TNF inhibitors have already failed

Sept 21, 2004 Zosia Chustecka

Lund, Sweden - Further data showing that rheumatoid arthritis (RA) patients

who have failed on TNF inhibitors are unlikely to respond to treatment with

the interleukin-1 (IL-1) blocker anakinra (Kineret, Amgen) have been

reported from Sweden [1].

" Patients whose RA fails to respond to TNF blockade rarely show any clinical

meaningful response to anakinra, " say Dr Tore Saxne and colleagues (Lund

University Hospital, Sweden) in a letter in the September 2004 issue of

Arthritis & Rheumatism. " The results in patients not previously treated with

biologic agents are also disappointing. "

Saxne et al say their results " support and extend " similar findings from a

UK group earlier this year in the same journal [2], reported at the time by

rheumawire. However, Dr Emilio (University of Texas Medical Branch,

Galveston, TX), who is a regular contributor the jointandbone.org forum,

points out that both groups base their conclusion on anakinra's inefficacy

after TNF inhibitors on a short trial of 3 months. tells rheumawire

that, in his experience, anakinra takes a long time to have a beneficial

effect, more than 6 months, and he has seen several patients go on to do

well on the interleukin-1 blocker (see below).

Swedish data from observational study

Saxne et al report data on 26 patients treated with anakinra, who were

identified from an observational study of biological agents in southern

Sweden with a database containing records on 1272 treated RA patients.

Of the 26 anakinra patients, 10 had not previously been treated with TNF

inhibitors, while 16 had. Of these, 7 had responded with a 20% improvement

(ACR20 response) but discontinued treatment due to side effects, while the

other 9 failed to achieve an ACR20 response.

Responses to anakinra treatment after 3 months

Anakinra treatment ACR20, no. of patients (%) ACR50, no. of patients

(%)

After stopping TNF inhibition because of side effects 4/7 (57) 2/7

(29)

After stopping TNF inhibitors because of inefficacy 2/9 (22) 0/9 (0)

Patients without prior TNF inhibitors 3/10 (30) 1/10 (10)

To download table as a slide, click on logo at the bottom of the page

These findings should be interpreted with caution, since the number of

patients is small, Saxne et al comment. But they are similar to those

reported earlier this year by Dr Maya Buch and colleagues (Leeds University,

UK), who also reported a lack of response after 3 months in 26 patients,

although in their report all of the patients had previously been treated

with TNF inhibitors.

Both groups say their data support the idea that both types of biologic

agents affect common pathways in the disease process. Consequently,

interleukin-1 antagonism in patients in whom TNF blockade was unsuccessful

is not an effective strategy, they conclude.

But is the IL-1 blockade incomplete?

However, Saxne et al also offer an alternative explanation. They suggest

that the low rate of response to anakinra is due to incomplete IL-1 blockade

and argue that " the possibility that IL-1 blockers with more favorable

pharmacokinetic/dynamic properties may be efficacious cannot be ruled out. "

This suggestion is " difficult to assess, " Buch et al comment in a reply to

the Swedes' letter [3]. " But the impressive results with anakinra treatment

of the periodic fever syndromes suggests that this agent is capable of

effectively blocking the IL-1 pathway, at least in the latter disease

groups. "

Maybe a longer trial is needed?

Approached by rheumawire to comment on these findings, says: " My

experience with a few patients has been that anakinra takes a long time to

have a beneficial effect, and during that period many physicians and

patients want to give up on it. Specifically, I remember a patient who

failed on infliximab and who had very active RA, basically unable to do much

at all. He was on methotrexate, Plaquenil, nonsteroidal anti-inflammatory

drugs [NSAIDS], and prednisone. We started anakinra, and it wasn't until 6

months later that he began to display a very significant clinical response.

He was a new man, as he told me. I was able to discontinue methotrexate and

discontinue prednisone. He continued to do well for about a year receiving

only anakinra, nothing else at all. He became active again, played golf, and

was able to travel. "

Although this is only one anecdote, says he has had similar

experiences with at least 4 more patients with chronic severe RA who also

improved significantly after treatment with anakinra.