Background/Purpose:

Etoricoxib, a selective
cyclooxygenase-2 (COX-2) inhibitor, provides symptom modification in RA
patients. Previous dose-ranging studies in RA demonstrated the clinical
efficacy of etoricoxib 90 mg vs placebo (PBO). In these studies, etoricoxib 60
mg demonstrated some clinically meaningful treatment effects, therefore the current
study further evaluated the efficacy of etoricoxib 60 mg and 90 mg in RA.

Methods:

This was a 2-part,
double-blind, PBO controlled study in RA. Part I (6 weeks) assessed the
efficacy of etoricoxib 60 mg and 90 mg vs PBO. Part II (6 weeks) evaluated
whether subjects with inadequate pain relief on etoricoxib 60 mg in Part I
benefitted from increasing to etoricoxib 90 mg in Part II.  Patients were ≥18
years of age, with a diagnosis of RA ≥6 months prior to screening and
prior clinical response to NSAIDs. Patients were required to have a disease
flare after NSAID washout prior to randomization. Eligible patients were
randomized to one of four treatment groups: PBO in Part I; etoricoxib 60 mg in
Part I & II; etoricoxib 60 mg in Part I followed by 90 mg in Part II; or etoricoxib
90 mg in Part I in a 2:7:7:8 ratio, respectively. Primary endpoints were
Disease Activity Score evaluating 28 joints and C reactive protein level
(DAS28-CRP) index and Patient Global Assessment of Pain (PGAP) score (0-100 mm
VAS) after 6 weeks of treatment in Part I. Safety
and tolerability measures included independent adjudication of all thrombotic
cardiovascular and serious upper GI AEs.

Results:

In total,
1404 patients were randomized; 83.5% were female; the mean age was 53.8 years,
75.4% were Caucasian, 1228 patients completed Part I and 713 patients continued
to Part II. Both 60 mg and 90 mg etoricoxib were superior to PBO for the
treatment of RA on both primary efficacy endpoints: change from baseline
DAS28-CRP score (Table 1A) and change from baseline PGAP score (Table 1B). For
DAS28-CRP, there was no significant treatment difference between etoricoxib 90
mg and 60 mg (Table 1A). Etoricoxib 90 mg demonstrated a small, but
statistically significant decrease in baseline PGAP score as compared to 60 mg (Table
1B). In Part II, inadequate pain responders did not experience a significant
decrease in PGAP score after increasing the etoricoxib dose from 60 mg to 90 mg
compared to inadequate pain responders who stayed on 60 mg (Table 1C). In
both etoricoxib 90 mg and 60 mg groups, the incidence of SAEs and drug-related
AEs were similar between the two treatment groups.

Conclusion:

Both
etoricoxib 90 mg and 60 mg are superior to PBO in relieving the symptoms of RA.
Etoricoxib 90 mg vs 60 mg resulted in a statistically significant, though
small, improvement in PGAP score, but not DAS28-CRP. Dose escalation from 60 mg
to 90 mg in pain inadequate responders did not significantly improve efficacy. Both
etoricoxib 90 mg and 60 mg were well tolerated and no new safety signals were
identified.