Schering-Plough Corporation today announced that the European Commission has approved the use of Remicade (infliximab) as monotherapy in the treatment of active and progressive psoriatic arthritis (PsA) in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated.
This label extension follows a positive opinion granted in June by the Committee for Medicinal Products for Human Use (CHMP), for the European Medicines Agency (EMEA).
Remicade, in combination with methotrexate, originally received approval for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease-modifying anti-rheumatic drugs in October 2004. Psoriatic arthritis is a chronic, autoimmune inflammatory condition involving the joints and the skin.
"For those psoriatic arthritis patients for whom the use of methotrexate is not appropriate, the approval of Remicade for use as a monotherapy offers a new treatment option for their disease," said Robert Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute.
The Remicade PsA extension is based on one-year data from Infliximab Multi-National Psoriatic Arthritis Controlled Trial 2 (IMPACT 2), a Phase III clinical study of 200 patients, with active PsA; and two-year data from the original IMPACT Trial, upon which the initial approval of Remicade in PsA was based. In the IMPACT 2 trial, the primary endpoint of joint improvement was met in Remicade-treated patients. At week 24 of treatment, 54 percent of patients achieved an ACR 20 response (a 20 percent collective improvement in rheumatoid arthritis symptoms) 41 percent had an ACR 50 response and 27 percent experienced an ACR 70 response. Furthermore, at week 54 of treatment, 53 percent of Remicade-treated patients achieved an ACR 20 response; with 33 percent and 20 percent experiencing ACR 50 and ACR 70 responses, respectively.
Also, a Psoriasis Area and Severity Index score of 75 (PASI 75) was seen in 60 percent of Remicade-treated patients at week 24, with nearly 49 percent of Remicade patients maintaining this response at week 54 of therapy. A PASI 75 score reflects a 75 percent improvement in disease symptoms. The prescribing information for Remicade has been revised to include these latest trial results specific to skin clearance.
"The joint involvement and often painful skin lesions associated with psoriatic arthritis, places an extraordinary burden on patients with this potentially progressive disease," said Douglas Veale, MD, Consultant Rheumatologists, University College of Dublin and St. Vincent's Hospital, Ireland. "In addition to the response of the joints, the PASI 75 response demonstrated in the IMPACT 2 trial should be a new treatment goal sought by rheumatologists who work with these psoriatic arthritis patients."
In the IMPACT and IMPACT 2 trials, patients treated with Remicade saw significant improvements in standard measures of disease activity; including number of swollen joints, number of painful and/or tender joints, dactylitis (finger or toe inflammation) and enthesopathy (inflammation involving the attachment of a tendon or ligament to bone.) Also, Remicade-treated patients in both trials saw disease improvement as early as week 2, with significant clinical response maintained through week 98 and 54 of treatment in IMPACT and IMPACT 2, respectively. Remicade efficacy was demonstrated in both trials, with or without concomitant use of methotrexate.
Patients treated with Remicade also saw significant improvements in physical function and health-related quality of life as measured with standardized questionnaires.
Elevated transaminase levels, which were noted with infliximab treatment during the first six months of IMPACT 2 and first year of IMPACT, were not disproportionately increased with an additional six months to one year of maintenance therapy. The elevations generally resolved with interruption or at times with continuation of therapy and were not associated with concomitant elevations in bilirubin or liver failure. While mild-to-moderate infusion reactions occurred, the PsA studies through one to two years of maintenance treatment demonstrated that there were no serious infusion reactions, delayed hypersensitivity or possible anaphylactic reactions.