Newswise — A potential new therapy called certolizumab pegol, when used in combination with methotrexate, may be safe and effective at treating active rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 2.1 million Americans have RA, most of them women.
Investigators followed 982 adult patients in a Phase III, multicenter, double-blind, placebo-controlled, 52-week study. Primary endpoints were clinical improvement according to a composite measure of disease activity, the ACR20, at week 24 and an improvement in the radiographic findings in joint x-rays (Sharp score) from the start to the end of the study. Secondary endpoints included ACR20 at week 52 and the more demanding ACR 50/ACR70 response rates at weeks 24 and 52. The ACR 20/50/70 scoring criteria measures improvement in tender and swollen joint count and improvement in at least three of the following five criteria: pain; level of disability; overall self-assessment; overall physician assessment; and acute phase reactant (e.g., C-reactive protein).
Patients received certolizumab pegol in three 400 mg doses given every two weeks, followed by doses of 200 mg or 400 mg every two weeks, or placebo. All patients were taking methotrexate therapy. Patients receiving certolizumab at either dose combined with methotrexate had significant improvement compared to patients taking only methotrexate, with up to 60% an ACR20 response and at least 20% an ACR70 response at weeks 24 and 52. Adverse events, including injection site reactions, were reported in both groups, the majority of which were considered mild to moderate.
"A unique aspect of certolizumab pegol is the rapid attainment of the high hurdle ACR50 and ACR70 responses by 12-16 weeks, compared to other TNF inhibitors which achieve these responses by about 24 weeks or more," said Edward Keystone, MD, University of Toronto, and lead investigator in the study. "Whether this is a reflection of the rapid entry of the pegylated molecule in the joint, remains unclear."
The American College of Rheumatology is the professional organization of and for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.
Editor's Notes: Dr. Keystone will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 2:30 " 4:00 pm ET on Thursday, November 8, 2007, in Grand Ballroom East.. Dr. Keystone will be available for media questions and briefing at 8:30 am ET on Saturday, November 10 in the on-site press conference room, Room 251.
Presentation Number: 700
The Anti-TNF Certolizumab Pegol in Combination with Methotrexate is Significantly More Effective than Methotrexate Alone in the Treatment of Patients with Active Rheumatoid Arthritis: 1-Year Results from the RAPID 1 Study
Edward Keystone1, David Mason2, Bernard Combe3. 1University of Toronto, Toronto, ON, Canada; 2UCB Inc, Smyrna, GA; 3Montpellier University Hospital, Montpellier, France
Purpose: The pro-inflammatory cytokine TNF-alpha plays an important role in several disease states, including rheumatoid arthritis (RA). Certolizumab pegol (CZP) is the first Fc-free, PEGylated anti-TNF to be studied in RA and selectively targets TNF-alpha in inflamed tissue with high affinity. The objective of the current study was to investigate the efficacy and tolerability of two dose regimens of CZP given subcutaneously as add-on therapy to methotrexate (MTX) in patients with active RA who were refractory to MTX monotherapy.
Methods: RAPID 1 was a Phase III, multicenter, double-blind, placebo-controlled, parallel-group, 52-week study. The co-primary endpoints were ACR20 at Week 24 and change in modified Total Sharp Score from baseline at Week 52. Secondary endpoints included ACR20 at Week 52 and ACR50/ACR70 response rates at Weeks 24 and 52. Patients, previously treated â‰¥6 months with MTX, were randomized 2:2:1 to treatment with CZP (three 400 mg doses every 2 weeks, followed by doses of 200 mg or 400 mg every 2 weeks) or placebo. MTX therapy was continued as usual. Efficacy and safety parameters were assessed at each visits. Patients who withdrew for any reason were considered non-responders from that point onwards
Results: We present efficacy and safety results. In total, 982 adult patients were randomized to treatment (intent-to-treat population [ITT]): CZP 200 mg, n = 393; 400 mg, n = 390; placebo, n = 199. Of these, 572 completed the study (n = 255, 274, and 43, respectively). At Weeks 24 and 52, the ACR20, ACR50, and ACR70 responder rates for patients receiving CZP were significantly greater than those for patients receiving placebo (Table). The proportion of patients who experienced an adverse event (AE) was 74.7% and 76.6% in the CZP 200 mg and 400 mg groups, respectively, and 57.8% in the placebo group. The majority of AEs were mild to moderate and discontinuation due to AEs was low (4.3%, 5.7% and 1.5% in the CZP 200 mg, 400 mg, and placebo groups, respectively).
[Table 1, ACR Responder Rates at Weeks 24 and 52 (ITT), available on request]
Conclusions: In MTX inadequate responders, CZP 200 mg every 2 weeks, after 3 initial doses of 400 mg, as add-on to MTX, showed a significant benefit in reducing the signs and symptoms of active RA compared with MTX alone at 24 weeks, with sustained results through 52 weeks. The higher dose of 400 mg every 2 weeks provided a similar benefit. Both doses were well tolerated, with a low incidence of discontinuation due to AEs.
Disclosure Block: E. Keystone, AstraZeneca, 2 Research grants; Bristol-Myers Squibb, 2 Research grants; Hoffman-La-Roche Ltd (Canada), 2 Research grants; Schering Plough Inc, 2 Research grants; Wyeth Pharmaceuticals, 2 Research grants; Centocor Inc, 2 Research grants; Abbott Laboratories, 2 Research grants; Novartis, 2 Research grants; Amgen, 2 Research grants; UCB, 2 Research grants; Abbott Laboratories, 5 Consulting fees; Amgen, 5 Consulting fees; Bristol-Myers Squibb, 5 Consulting fees; Centocor Inc, 5 Consulting fees; Chelsea Therapeutics, 5 Consulting fees; CombinatoRx, 5 Consulting fees; Genentech, 5 Consulting fees; GlaxoSmithKline Beecham, 5 Consulting fees; Hoffman La-Roche Ltd, 5 Consulting fees; Medarex, 5 Consulting fees; Schering Plough Inc, 5 Consulting fees; Wyeth Ayerst, 5 Consulting fees; UCB, 5 Consulting fees; Abbott Laboratories, 8 Speakers bureau; Amgen, 8 Speakers bureau; Bristol-Myers Squibb, 8 Speakers bureau; Centocor Inc, 8 Speakers bureau; Genentech, 8 Speakers bureau; Hoffman-La Roche Ltd, 8 Speakers bureau; Schering Plough Inc, 8 Speakers bureau; Wyeth, 8 Speakers bureau.