First evidence of benefit with bisphosphonate in RA

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Rheumawire

June 10, 2004 Nainggolan

First evidence of benefit with bisphosphonate in RA

Berlin, Germany - Evidence of a structural benefit of a bisphosphonate

in rheumatoid arthritis (RA) has been reported for the first time in a

cutting-edge-in-rheumatology session here at the EULAR 2004 meeting.

Although the idea of using bisphosphonates in rheumatoid arthritis seems

to be logical, these drugs have failed to live up to their promise in

clinical studies performed to date, explained Dr Steve Jarrett (Leeds

University, UK).

Nevertheless, there is a rationale behind the use of bisphosphonates in

RA, he said. Disordered bone metabolism, both systemic and local, is

clearly a feature of rheumatoid arthritis, which is also associated with

both generalized as well as periarticular osteoporosis. There is also

compelling evidence that joint erosion is crucially dependent on

osteoclast activity, Jarrett said, and " bisphosphonates are potent

inhibitors of osteoclast activity. "

But previous studies with this class of drugs in RA " have been of

limited success, " he said. However, these trials all used older drugs,

such as etidronate, pamidronate, and clodronate, whereas the new study

was performed using zoledronic acid (zoledronate). This has a much

higher bioavailability and is more potent than the other drugs, he

explained.

Zoledronic acid is a very long-acting bisphosphonate administered by

rapid intravenous infusion (15 minutes). The product is already marketed

(as Zometa®, Novartis) in many countries worldwide for use in the

treatment of hypercalcemia of malignancy and was recently also approved

for use in cancer patients with documented bone metastases. Its greatest

potential to date is seen to lie in osteoporosis treatment, for which it

offers the revolutionary option of once-yearly treatment, as previously

reported by rheumawire.

Jarrett and colleagues conducted a 6-month proof-of-concept study in 39

patients with new-onset RA (of less than 2 years' duration) and clinical

synovitis in the hand or wrist, who were all treated with background

methotrexate therapy [1]. They were randomized to zoledronic acid 5 mg

given at baseline and at week 13 (n=18) or to placebo (n=21) and were

followed out to 26 weeks.

There was a 61% reduction in the primary outcomeprogression of bone

erosionsin those treated with the bisphosphonate compared with those on

placebo, Jarrett said. There was also a reduction in secondary outcomes

with zoledronic acidincluding new erosions.

" This is the first evidence of structural benefit with bisphosphonate

therapy in RA as demonstrated by consistent results in all primary and

secondary end points in favor of zoledronic acid vs methotrexate alone, "

he said. He pointed out, however, that " most of the benefit was seen in

the wrist as opposed to the hand. "

The safety profile of zoledronic acid was similar to placebo, with a

lower proportion of patients in the bisphosphonate group experiencing

adverse events than in the placebo group. There were no renal

abnormalities reported in either group, Jarrett noted.

In a separate poster presentation tomorrow [2], Jarrett said his team

will also report that the quarterly infusions of zoledronic acid

increased bone-mineral density at clinically relevant sites over the 26

weeks of the study, compared with placebo, with particular treatment

benefits in the wrists and hands.

Concluding, Jarrett said, " Of course, further large studies are needed,

but maybe this is a sign that the osteoclast is a good target in RA. "

Sources

Jarrett S, O'Connor P, Conaghan P, et al. First

evidence of structural benefit from a bisphosphonate, zoledronic acid,

in rheumatoid arthritis. Presented at: EULAR 2004; Berlin, Germany; June

9-12, 2004. Abstract OP0002. :

Jarrett S, Conaghan P, Papanastasiou P, et al.

Profound effect of zoledronic acid on bone mineral density in rheumatoid

arthritis. Presented at: EULAR 2004; Berlin, Germany; June 9-12, 2004.

Abstract FRI0053.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org