New data on UCB’s anti-TNF biologic certolizumab pegol (Cimzia), disclosed this week in several poster presentations during the annual meeting of the American College of Rheumatology (ACR), show the treatment works well in rheumatoid arthritis (RA) patients irrespective of prior exposure to other biologics, and that results are sustained over 28 weeks. A new post-hoc data analysis from the RAPID 1 study also confirms that good responses to Cimzia seen by week 12 can predict benefits at one year in terms of reduced progression of joint damage visible on X-ray. Furthermore, other studies at ACR show Cimzia is safe and effective in Japanese RA patient populations as a monotherapy as well as when combined with methotrexate (MTX).
New findings reported from the large (n=1063) phase IIIb REALISTIC study, comparing Cimzia with placebo on top of usual therapy, looked at the 16-week open-label phase of this study that included a broad spectrum of patients with established active RA. In this phase all patients went on to receive Cimzia. Patients included 770 who were continuing on Cimzia with or without MTX or other disease-modifying anti rheumatoid arthritis drugs (DMARDs) having received it in the earlier 12 week double-blind phase, as well as 184 who were originally randomised to placebo on top of their other concomitant therapy. Patients in this study were more representative of those seen in clinical practice than those typically included in clinical trials, said investigators. All patients who completed the 12-week double blind phase entered the open-label phase and received 200mg Cimzia injections every other week alongside their usual anti-RA medications if any.
Lead investigator Dr Michael Weinblatt, consultant rheumatologist at Brigham and Women’s Hospital, Boston, MA, said: “It’s important to note this was not entirely a biologic-naïve population.” Over a third of patients entering the open-label phase, including those who received placebo in the double-blind phase, had prior exposure to anti-TNF therapies. Results from the double-blind phase showed patients adding Cimzia to their usual treatment did significantly better than those adding placebo as judged by the ACR20 response rate. Results from the open-label phase at 28 weeks revealed patients who responded to Cimzia did so irrespective of prior exposure to the drug. “Importantly, patients who didn’t respond to treatments that included placebo in the double-blind phase got the same response to Cimzia as people who had received Cimzia earlier (59.7% and 53.3%),” commented Dr Weinblatt. Around one in five patients in each category achieved remission as judged by DAS scores. Good responses to Cimzia seen among patients who originally received placebo were irrespective of whether or not they had previously failed other biologic treatments, he added. “People who failed prior anti-TNF drugs did pretty well and side-effect profiles were exactly as predicted.”
In the RAPID 1 post-hoc analysis involving 592 patients, it was found clinical outcomes seen on X-ray could be predicted from results seen at week 12 following response to treatment with Cimzia plus MTX. Deterioration in joint structure was assessed radiographically according to progression on the modified Total Sharp Score (mTSS).
“At week 52 fewer patients with good/moderate RAPID3 or EULAR responses at week 12 were mTSS progressors (defined as change from baseline in mTSS of >5 and >3) than those patients with poor responses,” reported investigators led by Edward Keystone, Rheumatologist at Mount Sinai Hospital, Toronto, Canada. The current analysis from this phase III double-blind placebo-controlled trial showed greater inhibition of radiographically-evident disease progression in patients treated with Cimzia plus MTX versus those treated with placebo + MTX. The majority of Cimzia 200mg +MTX-treated patients achieved good or moderate responses.
The findings were irrespective of whether the clinical response to MTX plus Cimzia or placebo had been judged according to EULAR’s strict objective and laboratory criteria (DAS28) or according to a subjective self-assessment rating carried out by patients themselves (RAPID3). This suggests that in future clinicians may be able to rely on the much less time-consuming patient judgments in RAPID3 (where scoring can be achieved in under 10 seconds) to help them decide whether to allow initiation of biologics to limit disease progression, the investigators said. However the EULAR criteria were a slightly better predictor of structural damage at week 52, they added.
Two double-blind placebo-controlled phase III studies from Japan show Cimzia performs as well in Japanese populations as in those of the rest of the world.
In the 316-patient J-RAPID study, Cimzia in fortnightly doses of either 100mg, 200mg or 400mg + MTX, was associated with a rapid and sustained reduction in RA signs and symptoms compared to placebo + MTX in Japanese patients with an inadequate response to MTX alone. Differences in response rates were evident as early as week 1 across all doses, said investigators.
In the 230-patient HIKARI study Cimzia was studied as monotherapy in Japanese patients unable to tolerate MTX. “This study was similar to the J- RAPID study except that a different dose of Cimzia (200mg every two weeks following an induction dose of 400mg) was used and this was prescribed without MTX,” said lead investigator Professor Kazuhiko Yamamoto, of the Department of Allergy and Rheumatology in University of Tokyo’s Graduate School of Medicine. A significantly improved clinical response was observed among patients receiving Cimzia alone or in combination with other DMARDs excluding MTX compared to placebo plus non-MTX therapy. “Having an effective monotherapy is important for the Japanese market because many patients are unable to tolerate MTX,” he explained. A high prevalence of pulmonary fibrosis precludes use of MTX in many Japanese patients.
“Although the dose of Cimzia used in the study was smaller than the typical dose used elsewhere, the response according to patients’ reports appeared better”, he commented. “We don’t know why this should be.”
UCB CMO Dr Iris Loew-Friedrich said the company is planning to file for a licence to market Cimzia in Japan early in 2012.
Last updated on: 14/11/2011 12:18:58