Pharmacy & Therapeutics - September 2008 - (Page 547)

MEETING HIGHLIGHTS: Digestive Disease Week a PGA response. Looking at patients with a PGA response according to baseline levels of C-reactive protein (CRP) (1 or higher, elevated, or less than 1) revealed no differences in 70% and 76% of patients, respectively. Adverse events were similar in all groups. “The results of these analyses,” Dr. Sandborn said, “demonstrate the incremental benefit of a second and third infusion of infliximab in patients with moderately or severely active ulcerative colitis.” tion was not more effective than infliximab maintenance therapy. He noted a high degree of success with both regimens. Dr. Lichtenstein commented in an interview, “By adding a drug such as methotrexate or steroids, you are just increasing the risk of serious adverse events.” Certolizumab Pegol (Cimzia) • Severine Vermeire, MD, University Hospital Gasthuisberg, Leuven, Belgium For patients in whom infliximab treatment failed because of loss of response or intolerance, certolizumab pegol (Cimzia, UCB Group) was ef ficacious in the 26-week open-label WELCOME trial, according to Dr. Vermeire. This pegylated humanized Fab´ fragment binds tumor necrosis factor-alpha (TNF- ). The trial’s aim was to assess the efficacy and safety of certolizumab pegol 400 mg SQ every two weeks for the induction of clinical response and remission in patients with moderateto-severe Crohn’s disease and a well-defined treatment failure with infliximab. Loss of infliximab response was defined as a CDAI score of more than150 points and a minimum increase of 70 points in the CDAI score at two consecutive visits, compared with the CDAI score at week six, Dr. Vermeire said. Acute infusion reactions to infliximab included one or more of the following during or within two hours of administration: hypotension, urticaria, flushing, facial or hand edema, throat tightness, oral cavity or lip edema, headache, or shortness of breath. Delayed reactions included rash, fever, polyarthralgia, or myalgias. The primary endpoint of the trial was response rate at week six. Enrolled patients (N = 539) were adults with a mean age of 35.9 years; 64% were female. Baseline CDAI scores ranged between 220 and 450. About 56% of patients had experienced loss of response only, 37% had hypersensitivity to infliximab only, and 6% had both. Eligible concomitant medications for Crohn’s disease included 5-acetylsalicylic acid (ASA); antibiotics; corticosteroids at a stable dose for two weeks; azathioprine; 6-MP; or methotrexate at a stable dose for eight weeks. Subjects were expected to remain on stable doses of these medications except for the corticosteroids, which could be tapered off after the eighth week. Clinical responses, consisting of a 100-point decrease in CDAI scores at week six and over the induction period, were reported in 61% of patients, and 68% of patients experienced a 70-point reduction. Analyses of concomitant medications, baseline CDAI scores, and reasons for stopping infliximab showed no differences among subgroups. Adverse events led to discontinuation of certolizumab pegol in 6.5% of patients. Dr. Vermeire concluded, “Certolizumab pegol 400 mg subcutaneously is an efficacious treatment for rapidly inducing response and remission in patients with moderate-to-severe Crohn’s disease for whom infliximab treatment has failed.” CROHN’S DISEASE Infliximab and Methotrexate • Brian Feagan, MD, Robarts Research Institute, London, Ontario, Canada • Gary Lichtenstein, MD, Director, Center for Inflammatory Bowel Disease, and Professor of Medicine, University of Pennsylvania, Philadelphia, Pa. In patients with active Crohn’s disease, adding methotrexate to infliximab (Remicade) conferred no added benefit. According to results of a 50-week, double-blind, multicenter, controlled trial, Dr. Feagan noted that although the patients requiring corticosteroid therapy have a poor prognosis, the best monotherapy rates for inducing and maintaining prednisonefree remission over a year are about 25%. Based on experience in rheumatoid arthritis, he said, combination therapy is the logical next step. Setting out to compare the efficacy and safety of combined infliximab and methotrexate with infliximab plus placebo, investigators enrolled 126 patients receiving induction therapy with prednisone 15 to 40 mg daily. The mean age of the patients (56% were men) was 39 years. Methotrexate 25 mg was given subcutaneously (SQ) weekly, and infliximab 5 mg/kg was given intravenously (IV) at weeks one, three, seven, and every eight weeks thereafter. Investigators evaluated disease activity using the Crohn’s Disease Activity Index (CDAI); global ratings; quality of life using the 36-item Short-Form Survey (SF-36); and CRP, an indicator of active inflammation; safety; and tolerability. Three criteria defined treatment success: a score of below 150 on the CDAI, no clinical need for prednisone supplements at week 14, and no relapse though week 50. A second primary endpoint was time to treatment failure. At week 14, treatment induction success rates were very high in both groups: 76.2% with infliximab/methotrexate and 77.8% with infliximab/placebo. At week 50, rates were 55.6% and 57.1%, respectively. Differences were not significant at either time interval. As for disease duration, an 80% success rate was noted for both groups at 50 weeks among patients with disease lasting less than two years, compared with 40% for disease lasting more than 12 years. Treatment success in patients with CRP levels below 4 mg/L was also similar in both groups. CDAI scores did not differ, but they trended in favor of infliximab alone (P = 0.09). Mean SF-36 scores were nearly identical at week 14 (46.6 for infliximab/methotrexate; 47.6 for infliximab alone). Maintenance therapy with infliximab plus methotrexate, Dr. Feagan noted, was well tolerated, although the combina- continued on next page Vol. 33 No. 9 • September 2008 • P&T® 547

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Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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