October 31, 2008 (San Francisco, California) — Two-year data on certolizumab pegol, a new pegylated tumor necrosis factor (TNF) inhibitor, show that the drug maintains efficacy in rheumatoid arthritis when used as add-on therapy to methotrexate and helps provide long-term improvement in physical function, health-related quality of life, and pain relief. The drug also improved work productivity when used as add-on therapy to methotrexate in a 6-month analysis of the RA Prevention of Structural Damage (RAPID) 1 and RAPID 2 trials, according to research presented here at the American College of Rheumatology (ACR) 2008 Annual Meeting.
"When you look at the totality of the evidence, you can see that certolizumab helps get people back to work, reduces symptoms, including fatigue, and shows long-term efficacy over 2 years," said Michael Schiff, MD, an investigator on the 2-year efficacy trial, and clinical professor of medicine at the University of Colorado, in Boulder.
The 1-year results of RAPID 1 trial were published online October 30 in Arthritis & Rheumatism. Investigators in that double-blind randomized controlled trial showed that ACR20 response rates in groups receiving 200 mg and 400 mg of certolizumab pegol were 58.8% and 60.8%, respectively, compared with 13.6% for placebo in patients who had previously failed to respond to methotrexate. The trial also showed that the drug had slowed mean radiographic progression from baseline by week 52, and improved physical function as early as week 1.
"The efficacy profile of certolizumab pegol appears to be very good; it has the advantage of being pegylated (and thus persists longer in the body)," Dr. Schiff told Medscape Rheumatology. "It's a good addition to our other TNF inhibitors."
In the 2-year open-label efficacy trial, patients received 400 mg of certolizumab pegol every 2 weeks, in addition to methotrexate. Subjects included those who had completed the RAPID 1 study at doses of 200 mg or 400 mg, and those that were withdrawn from the study at week 16 because they failed to achieve an ACR20 response. Analysis was carried out for completers of the study (n = 345) who had at least 2 years of exposure to certolizumab pegol. The results showed that ACR20 response rates ranged from 77% to 79%, ACR50 response rates ranged from 55% to 60%, and ACR70 response rates ranged from 35% to 36%.
Serious adverse events occurred in 21.1% of patients. Serious infections affected 7% of patients. Two cases of tuberculosis were reported, but there were no opportunistic infections. The investigators also reported 6 malignancies in the study population.
"Serious adverse events in the realm of 21% is not unusual for a 2-year study of a TNF inhibitor," Dr. Schiff noted.
In other abstracts presented at the meeting, the investigators showed that the quality-of-life improvement seen with certolizumab pegol in RAPID 1 was sustained in the open-label 2-year trial. The percentage of responders to the Health Assessment Questionnaire Disability Index minimum clinically important difference at week 100 ranged from 72.4% to 70.1%, and patients' pain was relieved on average by 38 to 39 points. Patients also reported a mean reduction in FAS score by 3.1 points at week 100.
In an analysis of work productivity for patients enrolled in the RAPID 1 and RAPID 2 clinical trials, the scientists also showed that patients experienced improvements in work productivity, compared with placebo. At 24 weeks, patients in the 200 mg and 400 mg groups had gained, respectively, 6.11 or 6.62 productive work days per month, compared with 0.24 days in the placebo group.
"This medicine is very interesting, because it remains in the system longer. And because it can be dosed less frequently, it's an attractive option," said rheumatologist Christopher Morris, MD, from Kingsport, Tennessee, and a member of the ACR Communications Committee.
"But as a practicing rheumatologist, I want to see proof that this is not just another 'me too' drug. We already have some good TNF inhibitors for rheumatoid arthritis. We know that patients respond quickly to this drug and have durability of response, but we'll also have to see how well patients tolerate the drug. If there are no problems that surface, it may have a place in pharmacology for rheumatoid arthritis," Dr. Morris said.
The studies described in this article were funded by UCB Pharmaceuticals. Dr. Schiff is a consultant for UCB. Dr. Morris has disclosed no relevant financial relationships.
American College of Rheumatology (ACR) 2008 Annual Scientific Meeting: Abstracts 975, 978, 980, and 981. Presented October 27, 2008.
Medscape Medical News © 2008 Medscape
Cite this: Barbara Boughton. Certolizumab Maintains Efficacy for 2 Years in Rheumatoid Arthritis Patients - Medscape - Oct 31, 2008.