Background/Purpose:

Etoricoxib 90 mg, a
selective COX-2 inhibitor, provides symptom relief in ankylosing spondylitis (AS)
patients. A prior study established etoricoxib 90 mg as safe and effective in
treating AS symptoms. The current study was conducted to determine the efficacy
and safety of etoricoxib 60 mg in AS patients.

Methods:

This was a 2-part,
double-blind, active comparator-controlled non-inferiority study in AS. Part I
(6 weeks) assessed the efficacy of etoricoxib 60 mg and 90 mg compared to
naproxen 1000 mg. Part II (6 weeks) evaluated whether subjects with inadequate
pain relief on etoricoxib 60 mg in Part I benefited from increasing to etoricoxib
90 mg in Part II.  Patients were ≥18 years of age with AS as classified
by the Modified New York criteria and a history of clinical response with
NSAIDs. Patients were required to have a disease flare after NSAID washout prior
to randomization. Eligible patients were randomized to naproxen; etoricoxib 60
mg in Part I & II; etoricoxib 60 mg in Part I 90 mg in Part II; or etoricoxib
90 mg in Part I & II in a 4:9:9:4 ratio respectively. The primary objective
was to compare the effect on spinal pain intensity (SPI) score (0 to 100 mm VAS)
after 6-weeks of treatment in Part I. The non-inferiority margin was set at 8 mm
for the SPI measure based on prior literature findings.  The overall safety and
tolerability of etoricoxib in AS patients was assessed including independent adjudication of all thrombotic
cardiovascular and serious upper GI AEs.

Results:

In total,
1015 patients were randomized; 70.9% were male; the mean age was 45.2 years, 84.6%
were Caucasian, 919 patients completed Part I and all continued to Part II. In
Part I, both etoricoxib doses were non-inferior to naproxen based on change in SPI
score from baseline (Table 1A). There was a mean decrease of ~2 mm SPI score for
etoricoxib 90 mg versus 60 mg; (Table 1B). Patients who had inadequate pain response
in Part I with 60 mg, had a small but significant improvement in SPI score after
switching to 90 mg (Table 1C). In both Part I and II, the incidences of AEs,
drug-related AEs, and SAEs were similar between the 3 treatment groups.
Independently adjudicated AEs were also similar between treatment groups).

Conclusion:

Both doses of etoricoxib
were non-inferior to naproxen. Etoricoxib 60 mg and 90 mg had similar efficacy in
relieving the pain associated with AS. Among inadequate responders to etoricoxib
60 mg, dose escalation to 90 mg daily resulted in a statistically significant
decrease in SPI score as compared to those subjects remaining on 60 mg. Both
etoricoxib 90 mg and 60 mg were well tolerated, and no new safety signals were
identified.