Remicade was highlighted in several indications at the 68th American College of Rheumatology annual meeting in San Antonio.
Remicade (infliximab), which was discovered by Malvern, Pa.-based Centocor Inc., is approved for both rheumatoid arthritis and Crohn's disease in North America, the European Union and Japan. In the EU, it is indicated for the treatment of ankylosing spondylitis in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.
In October, the EU approved expanded labeling for Remicade in combination with methotrexate in active and progressive psoriatic arthritis in patients who have responded inadequately to disease-modifying anti-rheumatic drugs (DMARDs). Remicade also is indicated in the EU for rheumatoid arthritis in combination with methotrexate for the reduction of signs and symptoms and improvement in physical function in patients with active disease when response to disease-modifying drugs, including methotrexate, has been inadequate. It is indicated in patients with severe, active and progressive rheumatoid arthritis not previously treated with methotrexate or other DMARDs.
Data were presented at the meeting showing significant and rapid improvements in arthritis and psoriasis in patients with active psoriatic arthritis.
In the IMPACT 2 (Infliximab Multinational Psoriatic Arthritis Controlled Trial) Phase III trial, Remicade provided a 70 percent improvement or greater (as measured by ACR 70) in symptoms of arthritis in 27 percent of patients, compared with 2 percent of patients on placebo at 24 weeks. Treatment with Remicade also resulted in a 90 percent or greater improvement in PASI score for nearly 40 percent of patients and 100 percent improvement in PASI score for 21 percent of patients, compared to none of the placebo patients.
Also, improvement in arthritis and psoriasis was seen by week two and maintained throughout the study. Remicade was efficacious in the treatment of dactylitis and enthesopathies, two manifestations of psoriatic arthritis causing pain and swelling.
New data from the ASPIRE (Active Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset) trial show that 79 percent of rheumatoid arthritis patients treated with Remicade plus methotrexate who began the study with no joint erosions, maintained an erosion-free state at one year, compared with 58 percent of patients treated with methotrexate alone. Also, in all patients, 64 percent in the Remicade-treated groups experienced no worsening in joint erosion scores, compared with 49 percent of patients receiving methotrexate alone.
Results were presented from the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial, showing that patients with active ankylosing spondylitis treated with Remicade had a median decrease of 73 percent in spinal inflammation activity scores at 24 weeks of treatment, while patients receiving placebo showed no effect, as measured by magnetic resonance imaging. The study included 266 patients.
Centocor is seeking approval for Remicade in ankylosing spondylitis in the U.S., and the FDA has accepted the supplemental biologics license application for that indication. Schering-Plough Corp., of Kenilworth, N.J., has Remicade rights outside the U.S., except in Japan and the Far East, where rights are held by Tanabe Seiyaku Ltd., of Osaka, Japan. Centocor is owned by Johnson & Johnson, of New Brunswick, N.J.
In other news from the meeting:
• Abbott Laboratories, of Abbott Park, Ill., reported new Phase III findings showing that patients with early rheumatoid arthritis experienced significant improvement in signs and symptoms while taking Humira (adalimumab) in combination with methotrexate as a first-line treatment. Specific data from the study, called PREMIER, show that methotrexate-naive patients with recent-onset rheumatoid arthritis might benefit from first-line early treatment with Humira and methotrexate, compared to either methotrexate or Humira alone. The effect of the combination therapy was observed as early as two weeks, and the differences were sustained throughout the two-year study. Other Phase III findings showed that active psoriatic arthritis patients who had failed a previous non-steroidal anti-inflammatory drug therapy achieved significant improvement in both joint and skin signs and symptoms after Humira treatment. Patients experienced sustained response with Humira therapy beyond the 12-week primary endpoint: at the 24-week follow-up, nearly one-fourth achieved a 70 percent improvement in arthritis signs and symptoms, and 42 percent achieved at least a 90 percent reduction in psoriasis activity.
• Amgen Inc., of Thousand Oaks, Calif., said 74.2 percent of rheumatoid arthritis patients treated with Enbrel (etanercept) plus methotrexate combination therapy experienced no progression of joint damage over a two-year span. The results are from the ongoing TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) trial. By comparison, 65.5 percent and 59.2 percent of Enbrel monotherapy and methotrexate monotherapy-treated patients, respectively, had no radiographic progression of joint damage at two years. Also, data showed that improvement in physical function scores were higher for the Enbrel combination group than either therapy alone. The TEMPO study randomized 686 patients with rheumatoid arthritis, of which 622 were included in the two-year radiographic analysis.
• Genmab A/S, of Copenhagen, Denmark, presented data with respect to the first 110 patients treated with AMG 714 (formerly HuMax-IL15) in a Phase II rheumatoid arthritis study. The data showed that at week 14, the primary endpoint, those taking the higher doses of AMG 714 had the greatest reduction in disease activity and the lowest frequency of disease flare up, while those on placebo often worsened. Although the data at week 14 are not statistically significant vs. placebo, it is an interim analysis of an ongoing pilot study that involves 180 patients. AMG 714 was well tolerated, and generated adverse events similar to that of placebo, Genmab said.
• Millennium Pharmaceuticals Inc., of Cambridge, Mass., and the Brigham and Women's Hospital presented results from seven studies in rheumatoid arthritis that they said could pave the way for the development of more effective, less toxic therapies designed based on a patient's genetic makeup. The research offered insight into genetic clues to better understand rheumatoid arthritis risk, underlying disease mechanisms and response to treatment. The studies were made possible by the rheumatoid arthritis patient registry Millennium established with Brigham and Women's Hospital in Boston in 2002.