SAN FRANCISCO, CA—Both the 90mg and 60mg doses of the selective COX-2 inhibitor etoricoxib are “superior” to placebo in relieving symptoms of rheumatoid arthritis (RA), concluded authors of a double-blind, randomized, placebo-controlled trial study presented at the 2015 ACR/ARHP Annual Meeting.
Treatment with etoricoxib 90mg resulted in a small significant improvement in Patient Global Assessment of Pain (PGAP) score; however, this was not observed using the Disease Activity Score evaluating 28 joints and C reactive protein level (DAS28-CRP) index, the study authors reported.
“These data provide evidence of a range of effective doses (60 or 90mg), which will allow for more individualized treatment recommendations by healthcare providers in the management of RA,” concluded Kara Bickham, MD, of Merck & Co., Inc., Kenilworth, NJ, and colleagues.
“Dose escalation from 60mg to 90mg in pain inadequate responders did not significantly improve efficacy,” she was quick to note, speculating that this might reflect a dose-response “ceiling effect.”
Based on previous results of dose-ranging studies that showed etoricoxib 60mg had “some clinically meaningful treatment effects,” the two-part study first assessed the efficacy of etoricoxib 60mg and 90mg vs. placebo in patients with RA for six weeks (Part I), then evaluated whether patients with inadequate pain relief on the 60mg dose benefited from an increase to the 90mg dose over an additional six weeks (Part II).
Patients were ≥18 years of age with a diagnosis of RA at least ≥6 months prior to screening and were required to have a prior clinical response to NSAIDs as well as a disease flare after NSAID washout prior to randomization.
The investigators randomly assigned 1,404 patients to one of four patient groups: placebo (Part I); etoricoxib 60mg (Part I); etoricoxib 90mg (Part II), or etoricoxib 90mg (Part I).
Primary end points were DAS28-CRP index and PGAP score (0-100 mm VAS) after six weeks of treatment in Part I.
Mean age of the patients was 53.8 years; 83.5% were female and 75.4% were Caucasian. A total of 1,228 patients completed Part I and 713 patients continued to Part II. Lack of efficacy and adverse events were the most common reason for discontinuation.
The results showed that both the 60mg and 90mg etoricoxib doses were superior to placebo for the treatment of RA on both primary efficacy end points. The difference in least square mean change in DAS28-CRP score between etoricoxib 60mg and placebo was -0.29 (P=0.004) and, for etoricoxib 90mg, -0.27 (P=0.034).
“For DAS28-CRP, there was no significant treatment difference between etoricoxib 90mg and 60mg,” Dr. Bickham reported.
The difference in least square mean change in PGAP score between etoricoxib 60mg and placebo was -7.99 (P<0.001) and, for etoricoxib 90mg, -10.70 (P<0.001). “Etoricoxib 90 mg demonstrated a small, but statistically significant decrease in baseline PGAP score as compared to 60mg,” she noted.
In Part II, those who were inadequate pain responders did not experience a significant decrease in PGAP score after the etoricoxib dose was increased from 60mg to 90mg when compared with inadequate pain responders who stayed on the 60mg dose (P=0.327).
“Both etoricoxib 90mg and 60mg were well tolerated and no new safety signals were identified,” she concluded.
A post-hoc analysis of baseline subgroups showed that for PGAP, DAS28-CRP, and Tender Joint and Swollen Joint counts, “greater improvement was observed with etoricoxib treatment versus placebo in those subjects with higher baseline scores when compared with those subjects with lower baseline scores,” Dr. Bickham said. “When comparing the two doses, the 90mg dose demonstrated greater improvement of scores compared with the 60mg dose in subjects who had higher baseline scores.”