Etoricoxib better than naproxen in ankylosing spondylitis

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Nov 5, 2002

Etoricoxib better than naproxen in ankylosing spondylitis

New Orleans, LA The new COX-selective inhibitor etoricoxib (Arcoxia®, Merck

& Co) showed efficacy superior to that of the traditional nonsteroidal

anti-inflammatory drug (NSAID) naproxen in the treatment of ankylosing

spondylitis (AS) in a 387-patient placebo-controlled trial reported at the

recent American College of Rheumatology meeting [1].

" This is the first time a COX-2 inhibitor has showed statistically

significant improvements over a nonselective NSAID in treating this highly

inflammatory disease, " Merck & Co noted in a press release issued at the

meeting. But in fact this is one of the first times ever that a coxib has

shown efficacy superior to that of a traditional NSAID in most other trials

in various conditions, including rheumatoid arthritis (RA) and

osteoarthritis (OA), the efficacy of various drugs in the 2 classes has

always been " comparable. " A notable exception is 1 other trial with

etoricoxib, in which it also showed efficacy superior to naproxen in a trial

in patients with RA; however, a second comparator trial with the 2 drugs in

RA showed comparable efficacy, Dr Alise Reicin, executive director of

clinical research at Merck & Co, told rheumawire.

Etoricoxib is currently available in Europe and in several South American

countries. In the US, however, the drug is currently not even awaiting

approval: a new drug application that had been filed in October 2001 was

withdrawn in March 2002. The company said in June 2002 that the FDA had

asked for more information, including additional safety data on

cardiovascular safety data vs comparators other than naproxen, as previously

reported by rheumawire.

Where it is available, the recommended doses for etoricoxib are 60 mg for

OA, 90 mg for RA, and 120 mg for acute pain and gout. The dose for AS is

likely to be 90 mg, as the 120-mg dose did not provide any additional

benefit, says Reicin.

Patients with AS assess their responses

The AS trial divided patients into 4 groups, taking placebo (n=93), naproxen

500 mg twice daily (n=99), or etoricoxib daily at 90 mg (n=103) or 120 mg

(n=92). At 6 weeks, the patients taking etoricoxib showed significantly

greater improvement compared with placebo (p<0.001) and also compared with

naproxen (p<0.05) on all 3 primary end points. There was no significant

difference in the effect of the 2 doses of etoricoxib. On the Patient Global

Assessment of Spine Pain, participants reported the spine pain that they

were feeling on a visual analog scale (VAS) that runs from 0 mm (none) to

100 mm (severe). Patients in the pooled etoricoxib group reported on average

a 29-mm decrease in spine pain from baseline compared with placebo vs a

21-mm decrease with naproxen. On the Patient Global Assessment of Disease

Activity, measured on a VAS running from 0 mm (very well) to 100 mm (very

poor), patients on etoricoxib reported an average 24-mm decrease in disease

activity from baseline compared with placebo vs an 18-mm decrease with

naproxen. On the Bath AS Functional Index, with a VAS from 0 mm (easy) to

100 mm (impossible), the etoricoxib patients scored an average decrease of

15 mm from baseline compared with placebo vs 11 mm for naproxen.

A secondary end point was the Patient Global Assessment of Response to

Therapy. The majority of patients in both etoricoxib and the naproxen groups

reported achieving a " good or excellent " response, but significantly more

patients achieved this response on etoricoxib (70.5% of the pooled groups)

than on naproxen (54.5%), the researchers noted. The incidence of

drug-related adverse experiences, gastrointestinal nuisance symptoms, and

hypertension and edema-related adverse events were similar across all 3

active treatment groups. The safety profiles of the 2 doses of etoricoxib

were " generally similar, " and no new or unexpected safety findings in this

patient population were observed.

Etoricoxib in gout efficacy comparable to indomethacin, but perhaps safer?

Separately, a recently reported trial in patients with acute gout

demonstrated etoricoxib of 120 mg daily to have efficacy equal to that of

indomethacin 50 mg 3 times daily but suggested that it may have an improved

safety profile [2]. Over the 8-day trial, the 2 drugs had a comparable

effect on various measures of pain and inflammation, with significant pain

relief reported at the first measurement, 4 hours after the first dose.

Overall adverse experience rates were similar between the 2 groups, note the

authors, but a prespecified safety analysis revealed that drug-related

adverse experiences occurred significantly less frequently with etoricoxib

(22.7%) than with indomethacin (46.7%) (p=0.003).

These findings support a potential role for selective COX-2 inhibitors in

managing gout, although they also raise important questions, says Dr Adel

Fam (Sunnybrook and Women's College Health Sciences Centre, Toronto). She

comments on the study in an editorial in this week's British Medical Journal

[3], saying: " Whether the treatment of acute gout with selective

cyclo-oxygenase inhibitors in place of the well-established NSAIDs will

prove to be more advantageous in terms of efficacy, gastrointestinal safety,

and cost-effectiveness remains to be shown in additional controlled studies.

These promising drugs may, however, be of particular benefit in patients who

are intolerant to nonselective NSAIDs and in those presenting with an acute

gouty attack of several days' duration since a longer course of treatment is

likely to be required. "