RESEARCH - Kineret (anakinra) is worth trying in RA after TNF inhibitors fail

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Anakinra is worth trying in RA after TNF inhibitors fail

Rheumawire

February 4, 2005

Zosia Chustecka

Denver, CO - Two previous reports have suggested that patients with

rheumatoid arthritis who have failed to respond to treatment with TNF

inhibitors are unlikely to respond to the interleukin-1 antagonist anakinra

(Kineret, Amgen). However, both reports were based on experience with only

26 patients, and other clinicians have told rheumawire of anecdotal cases

they have had of such patients responding and doing well.

Now, a report from a " real-world " database that included 192 such patients

concludes that anakinra may be of benefit and is worth considering in RA

patients who have not responded to TNF-inhibitor therapy. The new data,

reported by Dr Schiff (Denver Arthritis Center, CO) in a letter in

the January 2005 issue of Arthritis & Rheumatism [1], come from the

Rheumatoid Arthritis DMARD Intervention and Utilization Study (RADIUS 1).

This is a prospective multicenter observational study designed to

systematically document use patterns, effectiveness, and safety of

disease-modifying antirheumatic drugs (DMARDs) used in the treatment of RA,

Schiff explains. Between October 2001 and December 2002, this study enrolled

around 5000 RA patients who needed a new DMARD (either a switch or an

add-on) from 389 sites across the US.

An ad hoc analysis found 192 patients who started on anakinra and who had

previously been treated with a TNF inhibitor; most had discontinued because

of lack of efficacy (46.9%) and/or adverse effects (40.1%). The mean disease

duration was 11.2 years, and patients had received a mean of 3.2 prior

DMARDs. Of these 192 patients, most had tried only 1 TNF inhibitor, but 48

patients had tried 2 agents; as expected, these patients were considered by

their physicians to have more severe disease, Schiff comments.

Overall, these patients demonstrated improvements in all efficacy measures

after 6 months of anakinra therapy and, despite the need for daily

injections, continued to receive anakinra at 6 months, Schiff reports.

Significant improvements were seen in tender- and swollen-joint counts,

morning stiffness, and pain scores and on both physician and patient global

assessments. Patients who had discontinued 2 prior TNF inhibitors showed a

" more robust improvement " with anakinra therapy in patient-reported outcomes

than those who had previously tried only 1 TNF inhibitor, Schiff notes.

However, he suggests that it is the patients who discontinued TNF inhibitors

for safety reasons that may be good candidates for anakinra therapy, based

on " its excellent safety profile and current efficacy results. "

Another reason for the previous negative findings, in addition to the small

numbers involved, may be that the patients who were being treated had

disease that was more severe that that of patients seen typically at a

rheumatology practice, Schiff suggests. He notes that the series of 26

patients reported by the UK team [2] had an average disease duration of >15

years and had tried 5 prior DMARDs. " Patients with these disease

characteristics are not likely to respond to any treatment, " he comments.

In a reply [3], the UK team, headed by Dr Emery (University of Leeds),

agrees with both comments but points out that their study was prospective

and had clearly defined outcomes and very well-defined patient

characteristics. The participants were chosen specifically not only because

they had failed TNF-inhibitor therapy but also because the majority (23 of

26 patients) had primary inefficacy of TNF blockade. Because they had a pure

nonresponse to TNF inhibitors, they could have reasonably been expected to

have a more interleukin-1-driven disease, the team writes. But they had

virtually no measurable response to anakinra, and in fact had an outcome

that was worse than that seen in comparable patients not selected for

TNF-blockade resistance.

" We concur that patients who have discontinued TNF-antagonist therapy for

safety reasons may respond to anakinra therapy, " say Emery et al. But they

add: " We still strongly believe that patients with primary failure to TNF

blockade are not those with an IL-1-driven disease. "

Schiff hasreceived grant/research support, and acted as aspeaker

and/or consultant for the following companies: Angiotech, Abbott, Amgen,

Aventis, Bristol-Myers Squibb,Centocor, Genentech, Hoffman La-Roche, IDEC,

Novartis, Merck, and Wyeth-Ayerst.

Sources

Schiff M. Lack of response to anakinra in rheumatoid

arthritis following failure of tumor necrosis factor alpha-blockade: comment

on the article by Buch et al. Arthritis Rheum 2005; 52;364-365.

Buch MH, Bingham SJ, Seto Y, et al. Lack of response to

anakinra in rheumatoid arthritis following failure of tumor necrosis factor

alpha blockade. Arthritis Rheum 2004; 50:725-8.

Buch MH, Bingham SJ, Emery P. Author reply. Arthritis

Rheum 2005; 52;365.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org