NEW YORK (Reuters Health) - Sustained clinical improvements in signs and symptoms of rheumatoid arthritis are apparent within one week of initiating treatment with a novel pegylated TNF inhibitor -- certolizumab pegol -- added to ongoing methotrexate therapy, investigators report.
Certolizumab pegol consists of "a humanized Fab' fragment fused to a 40-kd polyethylene glycol moiety," designed to avoid complement- or antibody-dependent cytotoxicity or apoptosis, lead author Dr. Edward Keystone, at the University of Toronto, and colleagues explain in the November issue of Arthritis & Rheumatism. Pegylation increases the half-life of the drug to about 14 days, they add, and is believed to cause its preferential distribution to inflamed tissue.
The 52-week RAPID 1 (RA Prevention of Structural Damage 1) study was a phase III trial in which 982 patients with an inadequate response to methotrexate alone were randomized 2:2:1 to receive add-on treatment with subcutaneous certolizumab pegol at 200 mg, 400g, or placebo every 2 weeks.
"Improvements in all American College of Rheumatology (ACR) core set of disease activity measures, including physical function, were observed by week 1 with both certolizumab pegol dosage regimens," the investigators report. The improvements continued through 12 weeks of treatment and remained significant relative to placebo at week 52.
At week 24, the ACR20 response rates were similar for both active treatment groups, averaging about 60%, compared with 14% for placebo. At week 52, differences in ACR20, ACR50, and ACR70 responses were all significantly greater in patients taking certolizumab pegol versus placebo (p < 0.001 for all comparisons).
Radiographic evaluations showed that certolizumab pegol plus methotrexate inhibited the progression of structural damage, with mean change from baseline in the Sharp score of 0.2-0.4 Sharp units versus 2.8 Sharp units in placebo-treated patients (p < 0.001). Function was also superior, as assessed by the change from baseline in the disability index of the Health Assessment Questionnaire (p < 0.001).
Dr. Keystone's group reports that the adverse event rates were similar in all three arms of the trial, with about half in each group considered to be related to the study drug. None of the 8 deaths that occurred were attributed to the study drug. The numbers of serious infections and infestations per 100 patient years were 5.3 and 7.3 in the 200-mg and 400-mg certolizumab groups and 2.2 in the placebo groups.
"Combination therapy with certolizumab pegol plus methotrexate in these patients can thus be considered an effective treatment option," the team concludes.
