乌鸦传媒

WASHINGTON -- Efficacy and safety over 2 years of treatment were comparable among patients with moderate-to-severe rheumatoid arthritis (RA) receiving certolizumab pegol (Cimzia) or adalimumab (Humira), a prospective head-to-head study found.

At week 12, there was no difference in 20% improvements according to the criteria of the American College of Rheumatology (ACR20) between patients randomized to certolixumab (69.2%) or adalimumab (71.4%), for an odds ratio of 0.90 (95% CI 0.67-1.20, P=0.467), reported , of the University of Texas Southwestern Medical Center in Dallas.

And at week 104, similar numbers of patients in the two groups had achieved low disease activity according to the Disease Activity Score in 28 joints (DAS28), with 35.5% in the certolizumab group and 33.5% in the adalimumab group. This gave an odds ratio of 1.09 (95% CI 0.82-1.45, P=0.532), Fleischmann reported in a plenary session at the American College of Rheumatology annual meeting.

The study was simultaneously published online in .

Several studies have been conducted comparing the effects of treatment with tumor necrosis factor (TNF) inhibitors with biologic drugs with different mechanisms of action, but there have not yet been any head-to-head trials comparing the safety and efficacy of biologics within the same class, namely TNF inhibitors.

Fleischmann and colleagues addressed this knowledge gap in a 2 year study known as EXXELERATE, which was an investigator-blind superiority study comparing the early (12 week) and long-term (week 104) efficacy and safety of these two TNF inhibitors.

It was funded by certolizumab pegol's manufacturer, UCB Pharma, in hopes of demonstrating a benefit for its product over adalimumab. Those hopes were dashed.

"The study failed as a superiority trial for certolizumab," Fleischmann noted.

From 2011 to 2013, a total of 915 patients were enrolled and randomized to background methotrexate plus either to certolizumab in initial doses of 400 mg at weeks 0, 2, and 4 and then 200 mg once every 2 weeks, or to adalimumab, 40 mg every 2 weeks.

They had active disease that had not responded to methotrexate, but were biologics-naive.

Mean age was 53, almost 80% were women, and baseline DAS28 was 6.5.

At week 12, they were classified as responders if they had achieved a DAS28 of 3.2 or lower or a reduction in DAS28 of 1.2 or more. Patients who were nonresponders at that point were switched to the other group.

As with the primary endpoints of efficacy at weeks 12 and 104, no differences were seen between the two groups on any secondary endpoints, including achieving low disease activity in the certolizumab and adalimumab groups at different time points:

• Week 12, 30% vs 30%, OR 1 (95% CI 0.75-1.34)
• Week 24, 41% vs 37%, OR 1.19 (95% CI 0.90-1.57)
• Week 52, 42% vs 38% (OR 1.15, 95% CI 0.87-1.51)

Physical functioning also improved in both groups, with changes in the Health Assessment Questionnaire Disability Index of -0.62 in the certolizumab group and -0.72 in the adalimumab group.

Among primary nonresponders at week 12, 56% of those who switched from adalimumab to certolizumab became responders by week 24, as did 62% of those who switched from certolizumab to adalimumab.

"About 60% of primary nonresponders in either group, at week 12, did achieve a DAS28 response when switched to the second TNF inhibitor," Fleischmann said.

"Previously, it was postulated that patients who are primary nonresponders, as in EXXELERATE, are very unlikely to respond to treatment with a second TNF inhibitor and that these patients should switch to treatment with a drug with another mechanism of action," the investigators wrote.

"This is the only trial where we've proven that, as opposed to the popular misconception, a primary nonresponder when switched to a second TNF inhibitor did respond to a second anti-TNF agent," Fleischmann said.

"It is currently unclear why patients who fail one TNF inhibitor respond to another one, and this question is an important focus for future research," the group wrote.

Among those who switched to adalimumab at week 12, ACR20, ACR50, and ACR70 responses were seen in 40%, 17%, and 8%, respectively, while the corresponding numbers among patients who switched to certolizumab were similar, at 44%, 23%, and 11%.

Safety also was similar in the two groups, with serious adverse events occurring in 13% of the certolizumab and 11% of the adalimumab groups over the 2 years. Infections/infestations were reported in 59.9% and 59.1%. There were three deaths in each group, from causes such as coronary artery disease, pneumonia, and sudden death.

Limitations to the study included the inclusion of only two TNF inhibitors and a lack of patient blinding after week 12.